allopurinol and Gout

Several reports have suggested an association between febuxostat and muscle injury. The purpose of this study was to determine whether febuxostat increases the risk of muscle injury. This study included an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and a systematic review/meta-analysis of randomized controlled trials.. First, evaluation of the FAERS data included a disproportionality analysis that compared patients with and without rhabdomyolysis according to whether they were receiving febuxostat or allopurinol. Second, a systematic review/meta-analysis was performed to assess the risk of rhabdomyolysis and muscle injury in patients who used febuxostat or allopurinol.. Analysis of the FAERS data revealed disproportionality for increasing rhabdomyolysis in patients who received febuxostat (reporting odds ratio 4.49, 95% confidence interval [CI] 3.72-5.38, P < .01) and allopurinol (reporting odds ratio 2.49, 95% CI 2.25-2.75, P < .01). Nineteen studies were eligible for inclusion in the systematic review/meta-analysis. Rhabdomyolysis was reported in only 1 study. The risk of any type of muscle damage was not significantly increased with febuxostat compared with placebo (risk ratio 0.92, 95% CI 0.73-1.17, P = .52, I. Febuxostat does not seem to affect the risk of muscle injury. However, the findings of this meta-analysis indicate a need for further high-quality observational studies with long-term follow-up.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Muscles; Muscular Diseases; Randomized Controlled Trials as Topic; Rhabdomyolysis

Introduction Gout in Aotearoa New Zealand (NZ) remains an equity issue. The prevalence in Pacific and Māori people is one of the highest internationally. Although Pacific and Māori experience earlier onset and higher burden of gout, which can severely impact their quality of life, their management of it is often sub-optimal. Aim To conduct a scoping review of the NZ literature for interventions to improve the uptake/management of allopurinol for gout and their evaluation. Methods Databases Medline, Scopus, Embase, and CINAHL Plus and the grey literature were searched systematically to identify all NZ intervention studies aiming to improve allopurinol uptake for gout treatment. Interventions included: if they were delivered in NZ, aimed to improve allopurinol uptake, and were provided in English. A narrative approach was used to extract and synthesise data. Results Eighteen peer-reviewed and grey literature publications met the search criteria. Interventions clustered into three domains: multifaceted or multi-practitioner; gout app; and online booklets or fact sheets. Serum urate levels improved in multi-faceted or multi-practitioner interventions only, whereas the gout app only improved patients' awareness and understanding of gout and medications. Online fact sheets and booklets need more active utilisation from health professionals to improve gout health literacy. Discussion Most gout interventions in NZ use multifaceted or multi-practitioner approaches. Although most interventions successfully controlled serum urate levels and improved equitable access for gout patients to urate-lowering therapy, these interventions did not sustain retention, completion, and engagement for certain population groups, particularly Pacific and Māori, who experience a higher burden of gout.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; New Zealand; Quality of Life; Uric Acid

The natural products have a new chemical structure and biological active diversity, so they are favored by scientific researchers. Gout is a high incidence and high-risk disease, and the current treatments are not satisfactory. Xanthine oxidase (XO) is a key enzyme responsible for the development and progression of various metabolic and oxidative stress-related diseases. Excessive activity of XO leads to elevated serum urate levels, which in turn leads to the development of hyperuricemia. This review mainly introduces the recent progress of the new research on the anti-gout activity of natural products that could provide new treatment methods for gout and information for the discovery and development of new anti-gout drugs.

Topics: Biological Products; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Xanthine Oxidase

Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout. However, not all patients receiving oral ULT achieve the target serum urate level, in part because some patients cannot tolerate, or have actual or misconceived contraindications to, their use, mainly due to comorbidities. ULT dosage is also limited by formularies and clinical inertia. This failure to sufficiently lower serum urate levels can lead to difficult-to-treat or uncontrolled gout, usually due to poorly managed and/or under-treated gout. In species other than humans, uricase (urate oxidase) converts urate to allantoin, which is more soluble in urine than uric acid. Exogenic uricases are an exciting therapeutic option for patients with gout. They can be viewed as enzyme replacement therapy. Uricases are being used to treat uncontrolled gout, and can achieve rapid reduction of hyperuricaemia, dramatic resolution of tophi, decreased chronic joint pain and improved quality of life. Availability, cost and uricase immunogenicity have limited their use. Uricases could become a leading choice in severe and difficult-to-treat gout as induction and/or debulking therapy (that is, for lowering of the urate pool) to be followed by chronic oral ULT. This Review summarizes the evidence regarding available uricases and those in the pipeline, their debulking effect and their outcomes related to gout and beyond.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Hyperuricemia; Quality of Life; Urate Oxidase; Uric Acid

Gout is characterized by hyperuricemia and the deposition of monosodium urate (MSU) crystals around joints. Despite the availability of several drugs on the market, its treatment remains challenging owing to the notable side effects, such as hepatorenal toxicity and cardiovascular complications, that are associated with most existing agents. This perspective aims to summarize the current research progress in the development of antigout agents, particularly focusing on xanthine oxidase (XO) and urate anion transporter 1 (URAT1) inhibitors from a medicinal chemistry viewpoint and their preliminary structure-activity relationships (SARs). This perspective provides valuable insights and theoretical guidance to medicinal chemists for the discovery of antigout agents with novel chemical structures, better efficiency, and lower toxicity.

Topics: Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid; Xanthine Oxidase

The global burden of gout is rising, as are the prevalence of associated comorbidities, all-cause mortality and societal costs. In this review, we discuss recent advances in epidemiology and treatment strategies for gout.. Genetic factors and obesity are prominent contributors to hyperuricemia and gout, while dietary factors contribute to less variance in serum urate, though can still have some contribution to population attributable risk. A consensus statement by the Gout, Hyperuricemia and Crystal-Associated Disease Network outlined appropriate terminology regarding gout, which will aid in communication about various aspects of the disease. The 2020 American College of Rheumatology gout guideline offers comprehensive evidence-based recommendations for the management of hyperuricemia using urate-lowering therapy, prophylaxis when initiating urate-lowering therapy, treatment of gout flare and adjunctive management strategies. There is improved understanding of risk factors for allopurinol hypersensitivity syndrome and well tolerated use of allopurinol in chronic kidney disease. Trial data have provided new insights regarding cardiovascular risk with febuxostat. Several new drug therapies are being tested for both urate-lowering efficacy and gout flare management.. Although there have been significant advances in understanding of risk factors and treatment approaches, gout remains suboptimally managed. There is substantial need for improving gout management efforts and gout education among patients and clinicians.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Symptom Flare Up

Gout is the most common form of inflammatory arthritis affecting millions of persons around the world. Painful flares and tophaceous deposits are debilitating, reduce quality of life and put strain on health-care systems.. This review provides an overview of the treatment of gout flares and lowering serum urate. First line agents are discussed with emphasis on emerging evidence. Novel therapies are also covered.. Lifestyle modifications form a part of gout prevention. NSAIDs, colchicine, and glucocorticoids are first line agents for gout flares. The IL-1β antagonists are highly effective for arresting flares but their cost-effectiveness render them salvage therapies. Allopurinol is an agent of first choice for urate lowering therapy. In Southeast Asian and Black populations, screening for HLA*B58:01 mutation is a cost-effective approach to decrease the occurrence of allopurinol hypersensitivity syndrome. Febuxostat is another efficacious urate lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety. Novel uricosurics are a class for continued drug development; verinurad and arhalofenate are agents with future promise. For patients with recalcitrant gout, pegloticase is effective. Its immunogenicity significantly threatens the achievement of sustained urate lowering responses. Abrogating pegloticase's immunogenicity with immunomodulatory co-therapy may lend to sustained efficacy.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Quality of Life; Uric Acid

Refractory, or uncontrolled, gout is a chronic, progressive, inflammatory arthropathy resulting from continued urate deposition after failed attempts to lower serum uric acid below the therapeutic threshold with oral urate-lowering therapies such as allopurinol and febuxostat. Recombinant uricase is increasingly being used to treat refractory gout; however, the immunogenicity of uricase-based therapies has limited the use of these biologic therapies. Antidrug antibodies against biologic therapies, including uricase and PEGylated uricase, can lead to loss of urate-lowering response, increased risk of infusion reactions, and subsequent treatment failure. However, co-therapy with an immunomodulator can attenuate antidrug antibody development, potentially increasing the likelihood of sustained urate lowering, therapy course completion, and successful treatment outcomes. This review summarizes evidence surrounding the use of immunomodulation as co-therapy with recombinant uricases.

Topics: Allopurinol; Antibodies; Gout; Gout Suppressants; Humans; Urate Oxidase; Uric Acid

Gout, the most common inflammatory arthritis worldwide, is an auto-inflammatory metabolic disease that leads to monosodium urate crystal deposition. Hyperuricaemia is a significant risk factor for the development of gout; however, hyperuricaemia alone is not sufficient to induce gout.Gout flares have circadian rhythms. Gout flares vary during the day and have strong seasonality, with flares being more common in the spring. The reasons for the predominance of flares in the spring are unclear since serum urate (SU) levels show seasonal variation; however, SU levels are highest in the summer.Immune function varies significantly throughout the year, with enhanced immune responses increasing during the winter. In addition, chronic disruption of circadian rhythms is associated with metabolic syndrome and diseases driven by metabolism. The most telling example relates to Xanthine oxidase (XOD/XDH). The analysis of XOD/XDH established its circadian regulation and demonstrated that inhibition of the activity of XOD is characterised by distinct, crossregulating diurnal/seasonal patterns of activity.The gastrointestinal microbiota of gout patients is highly distinct from healthy individuals. In a small series of gout patients, Bacteroides caccae and Bacteroides xylanisolvens were found to be enriched. Bacteroidales levels were highest during the spring and summer, and loading values were highest in the spring.Our review discusses gout's circadian rhythm and seasonality, possible influences of the microbiome on gout due to our new knowledge that Bacteroidales levels were highest during spring when gout is most common, and potential opportunities for treatment based on our current understanding of this interaction.

Topics: Arthritis, Gouty; Gout; Gout Suppressants; Humans; Hyperuricemia; Microbiota; Symptom Flare Up; Uric Acid; Xanthine Oxidase

In this review, we report on new findings regarding associations of uric acid with kidney health. We discuss kidney stones, effects of uric acid in chronic kidney disease (CKD), and management of gout in CKD. Recent studies on neuroprotective effects of raising uric acid provide interesting data regarding nephrolithiasis.. Elevated urate levels have been implicated in the progression of chronic kidney disease (CKD), but the results from PERL and CKD-FIX studies did not demonstrate that allopurinol slowed CKD progression. The SURE-PD3 sought to determine if increasing uric acid would slow the progression of Parkinson's disease. Results ultimately did not support this hypothesis, but high urinary uric acid levels caused uric acid stones, not calcium stones. Low urinary pH remains the key to the formation of uric acid stones. Thiazolidinediones improve insulin resistance, which is associated with an increase in urine pH. The most recent research has not supported the hypothesis that lowering serum uric acid levels will slow the progression of CKD or provide neuroprotection in Parkinson's disease. It is still unclear as to why uric acid stone formers have a high net acid excretion. The STOP-GOUT trial demonstrates that there was a lack of significant adverse events with higher urate-lowering dosages of allopurinol and febuxostat, despite patients' kidney function. This may push other studies to administer higher dosages per ACR guidelines. Future studies could then demonstrate decreased progression of CKD.

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Kidney; Male; Parkinson Disease; Renal Insufficiency, Chronic; Uric Acid

Inhibition of xanthine oxidase (XO) is an effective and most prominent therapeutic approach for the management of gout. Discovery of its association in the pathophysiology of diabetes, cardiovascular disorders, etc., widened its therapeutic horizons. Limited drug candidates in clinical practice along with side effects forced researchers to develop more efficacious and safer XO inhibitors for the management of gout and other disorders associated with XO hyperactivity. In this regard, this review focus on (a) various drug candidates in clinical practice and under clinical trials, (b) Development of various heterocyclic motifs as XO inhibitors in last two decades and (c) various patented synthetic XO inhibitors.

Topics: Enzyme Inhibitors; Gout; Humans; Xanthine Oxidase

This study aimed to compare the risk of dementia between exposed to allopurinol and not exposed to allopurinol in persons who had gout and/or hyperuricemia.. The meta-analysis was conducted to select case-control research written in English through the help of PubMed and Web of Science. The pooled odds ratio (OR) with 95% confidence interval based on the fixed-effect model was applied to compare the allopurinol exposure among cases (subjects with dementia) and controls (subjects without dementia).. A total of 4 case-control studies relating the allopurinol exposure to the risk of dementia were identified. The study duration was from 9 to 14 years. The number of study persons was from 3148 to 137,640. The male percentage of study subjects was from 36.9 to 62.5. The mean age of study persons was from 72.3 to 78.7 years. Overall, the odds of the allopurinol exposure among cases were lower than the odds of the allopurinol exposure among control subjects (OR = 0.91, 95% confidence interval = 0.87-0.95, P < .001). The heterogeneity between these eligible studies was low (I² = 0%). The sensitivity analysis revealed that after excluding the studies with concern, the pooled OR did not achieve statistical significance.. This is the first meta-analysis to report that there is a negative relationship between the allopurinol exposure and the risk of dementia. Although the results favor the hypothesis, currently it is unable to draw strong conclusions about the protective effect of allopurinol against dementia due to inclusion of only a few eligible studies. Randomized controlled trials are needed to explore the relationship between allopurinol exposure and the probability of dementia.

Topics: Aged; Allopurinol; Case-Control Studies; Dementia; Gout; Gout Suppressants; Humans; Male

Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus.. We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis.. Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment (. Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients' renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.

Topics: Allopurinol; Diabetes Mellitus; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney; Uric Acid

To evaluate the major cardiovascular (CV) events of febuxostat compared to allopurinol for the treatment of gout or asymptomatic hyperuricemia.. Relevant studies published until August 15, 2020 were identified by a systematic search of the PubMed and Wiley Online Library databases. Any controlled clinical trial, randomised controlled trial (RCT), retrospective cohort study or open label trial (OLT) comparing febuxostat in patients with gout or hyperuricemia with allopurinol. The quality of all identified studies was assessed based on Cochrane Collaboration's risk of bias tool. Odds ratios (OR) were calculated with random effects and reported with corresponding 95% confidence intervals (CI).. Eighteen studies were ultimately included in the analysis, among them 6 articles mentioned serum uric acid (sUA) level before and after treatment, 14 articles mentioned major cardiovascular events, 5 articles mentioned cardiovascular death, 6 articles mentioned skin reactions, 6 articles mentioned musculoskeletal and connective tissue signs and symptoms, 4 articles mentioned joint-related signs and symptoms, 6 articles mentioned upper respiratory infection, 5 articles mentioned gastrointestinal reaction and 7 articles mentioned all-cause mortality. The febuxostat group showed significantly lower sUA levels than allopurinol group (MD =-0.83, 95% CI: -1.22 to -0.44, P<0.0001, I2=98%). There was no markedly difference between the febuxostat and allopurinol (OR 1.01, 95% CI: 0.83 to 1.23, P=0.84, I2=95%) in the major cardiovascular events. The occurrence of skin reactions of febuxostat was significantly fewer than allopurinol (OR 0.55, 95% CI: 0.42 to 0.73, P<0.0001, I2=49%). Regarding to occurrence of CV death, musculoskeletal and connective tissue signs and symptoms, febuxostat group was higher than allopurinol group. However, among patients with gout or hyperuricemia, treatment with febuxostat resulted in other adverse reactions, including all-causes mortality similar to those associated with allopurinol.. The limitation of the study was the included studies show high heterogeneity in regard to their design. There was no difference in the incidence of major cardiovascular events between febuxostat and allopurinol, and febuxostat was better in lowering uric acid and has less adverse skin reactions than allopurinol, but the risk of CV death of febuxostat was higher than allopurinol.

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid

Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent.. To assess the efficacy and safety of dietary supplementation for people with chronic gout.. We updated the original search by searching CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers (August 2020). We applied no date or language restrictions. We also handsearched the abstracts from the 2010 to 2019 American College of Rheumatology and European League against Rheumatism conferences, and checked the references of all included studies.. We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement, or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents, and vitamins. The major outcomes were acute gout flares, study withdrawal due to adverse events (AEs), serum uric acid (sUA) reduction, joint pain reduction, participant global assessment, total number of AEs, and tophus regression.. We used standard methodological procedures expected by Cochrane.. Two previously included RCTs (160 participants) met our inclusion criteria; we did not identify any new trials for this update. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP, and sUA reduction for vitamin C), we reported the results separately. One trial (120 participants), at unclear risk of selection and detection bias, compared SMP enriched with glycomacropeptides (GMP) with un-enriched SMP, and with lactose, over three months. Participants were predominantly men, aged in their 50s, who had severe gout. The results for all major outcomes were imprecise, except for pain. None of the results were clinically significant. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were not clinically significant (mean (standard deviation (SD)) flares per month: 0.49 (1.52) in SMP/GMP/G60 group versus 0.70 (1.28) in the control groups; absolute risk difference: mean difference (MD) -0.21 flares per month, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar between groups (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03); there were 4% more withdrawals in the SMP/lactose groups (10% fewer to 18% more; low-quality evidence). Serum uric acid reduction was similar across groups (mean (SD) -0.025 (0.067) mmol/L in SMP/GMP/G60 group versus -0.010 (0.069) in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). Pain from self-reported gout flares (measured on a 10-point Likert scale) improved slightly more in the GMP/G600 SMP group compared with controls (mean (SD) -1.97 (2.28) in SMP/GMP/G600 group versus -0.94 (2.25) in control groups; MD -1.03, 95% CI -1.89 to -0.17). This was an absolute reduction of 10% (95% CI 20% to 1% reduction; low-quality evidence), which may not be of clinical relevance. The risk of adverse events was similar between groups (19/40 in SMP/GMP/G600 group versus 39/80 in control groups; RR 0.97, 95% CI 0.66 to 1.45); the absolute risk difference was 1% fewer adverse events (1% fewer to 2% more), low-quality evidence).. While dietary supplements may be widely used for gout, this review found no high-quality that supported or refuted the use of glycomacropeptide-enriched skim milk powder or vitamin C for adults with chronic gout.

Topics: Adult; Aged; Allopurinol; Animals; Dietary Supplements; Gout; Humans; Male; Middle Aged; Milk; Powders

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

Topics: Animals; Atherosclerosis; Comorbidity; Diabetes Mellitus, Type 2; Gout; Humans; Hypertension; Hyperuricemia; Metabolic Syndrome; Oxidative Stress; Reactive Oxygen Species; Renal Insufficiency, Chronic; Risk Factors; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome

Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout.. Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to August 2018. Articles eligible for inclusion used a cohort design and examined cardiovascular or all-cause mortality in patients diagnosed with gout and prescribed allopurinol. Information on study characteristics, design, sample size, and mortality risk estimates were extracted. Article quality was assessed using the Newcastle-Ottawa Scale. Included articles were described in a narrative synthesis and, where possible, risk estimate data were pooled.. Four articles reported a hazard ratio (HR) risk estimate for all-cause mortality in patients with gout using allopurinol, and 2 of these also reported cardiovascular mortality. Two articles found allopurinol to be protective in patients with gout, 1 found no statistically significant association, and 1 found no statistically significant effect of escalation of allopurinol dosage on all-cause or cardiovascular-related mortality. Data pooling was possible for all-cause mortality and found no association between allopurinol use in patients with gout and all-cause mortality compared to patients with gout not using allopurinol (adjusted HR 0.80 [95% confidence interval 0.60-1.05]).. There was no significant association between all-cause mortality and allopurinol use in people with gout. However, the number of included studies was small, suggesting that further studies are needed.

Topics: Adult; Aged; Allopurinol; Cause of Death; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

To assess the efficacy and safety of the commonly used urate-lowering therapies (ULTs): febuxostat, allopurinol, and lesinurad in hyperuricemic patients with gout.. We included all randomized controlled trials (RCTs) that compared ULTs with placebo or head to head. The primary efficacy endpoint was the proportion of subjects achieving the target serum urate (SU) level at month 6. Safety outcomes included total adverse events (AEs), serious AEs, withdrawals due to AEs, and AEs per organ system. A Bayesian network model was used to compare all ULTs with placebo and among themselves.. Fifteen RCTs were included for the analysis, in which 7968 patients were randomly assigned to take either placebo or one of 11 ULTs: allopurinol, febuxostat 40/80/120/240 mg/day, lesinurad 400 mg/day, lesinurad 200/400/600 mg/day plus allopurinol, and lesinurad 200/400 mg/day plus febuxostat. All ULTs were effective in achieving the target SU level at month 6 compared with placebo (ORs between 26.81 and 1928). Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. Furthermore, the lesinurad combination with xanthine oxidase inhibitor (XOI) groups had a higher proportion of patients achieving the target SU level than the febuxostat 40 mg/day group (ORs between 2.89 and 9.17), the allopurinol group (ORs between 3.56 and 11.27), or the lesinurad 400 mg/day monotherapy group (ORs between 12.30 and 39.17) but might have a high risk of AEs.. All ULTs are effective in achieving the target SU level compared with placebo in hyperuricemic patients with gout. Lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to XOI monotherapy. Key Points • All urate-lowering therapies (ULTs) were effective in achieving the target serum urate (SU) level at month 6 compared with placebo in hyperuricemic patients with gout. • Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. • Lesinurad in combination with febuxostat or allopurinol was effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of AEs.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid

Xanthine oxidase (EC 1.17.3.2) (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy includes XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist, intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.

Topics: Biological Products; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Oxidoreductases; Plant Extracts; Xanthine Oxidase

Gout, inflammatory arthritis caused by the deposition of monosodium urate crystals into affected joints and other tissues, has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades.. In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high, and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta- activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore, the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design.. In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.

Topics: Gout; Gout Suppressants; Humans; MAP Kinase Kinase Kinases; Molecular Targeted Therapy; Xanthine Oxidase

Gout continues to increase in prevalence in developed countries with Oceanic countries particularly affected. Both gout and hyperuricaemia are associated with the metabolic syndrome and its sequelae. Recently, the Australian Institute for Health and Welfare (AIHW) reported a prevalence rate of 0.8% which appeared incongruous with other published research. Thus, an updated systematic review was undertaken to review the literature on the prevalence of gout and hyperuricaemia in Australia from data published after 2011.. A comprehensive, systematic search was conducted in MEDLINE, Embase and Web of Science in addition to relevant websites to identify research reporting the prevalence of gout and/or hyperuricaemia in Australia from May 2011 until June 2020. Crude gout and hyperuricaemia prevalence data was obtained and presented alongside case ascertainment, time-period, age range and stratified by gender if available.. 118 full text articles were screened. 12 articles were included for analysis of gout prevalence. 4 articles were identified for the hyperuricaemia analysis. Wide variation in prevalence figures exist largely due study design and sample age range. Studies using a case definition of self-reported diagnosis of gout reported prevalence rates between 4.5% and 6.8%. The remaining studies used either electronic coding data from general practitioners or wastewater estimation of allopurinol consumption and documented adult prevalence rates between 1.5% and 2.9%. Prevalence increases with age, male sex and over time in keeping with global data. Hyperuricaemia prevalence ranged between 10.5% and 16.6% in Caucasian or an Australian representative population. AIHW estimates applied a chronic condition status, defined as current and lasted or expected to last more than six months, to cases of gout in the Australian National Health Survey. This likely results in an under-estimation in reported Australian gout prevalence rates.. Gout is highly prevalent in Australia compared to global comparisons and continues to increase over time. Hyperuricaemia prevalence is also high although contemporary data is limited.

Topics: Adult; Allopurinol; Australia; Gout; Humans; Hyperuricemia; Male; Prevalence

To review recent literature with relevance to the management of multimorbid patients with gout, i.e., gout medication repurposed for comorbidities and vice versa.. Adding to the previous success of interleukin-1 inhibition, two trials on low-dose colchicine's role in cardiovascular disease (CVD) demonstrated potential benefits in patients with or without gout. In Colchicine Cardiovascular Outcomes Trial, a composite CVD endpoint was reduced by 23% among patients who had experienced a recent myocardial infarction. In Low-Dose Colchicine 2, the composite CVD endpoint was reduced 31% among those with stable coronary artery disease. Use of urate-lowering therapy (ULT) for renal protection in patients without gout produced null results. Allopurinol did not benefit the glomerular filtration rate in two trials (Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Function Loss) among patients with chronic kidney disease (with or without hyperuricemia, but not gout). SGLT-2 inhibitors, a medication recommended for patients with diabetes and CVD, diabetic kidney disease, or heart failure, demonstrated a protective effect against gout flares in a secondary trial analysis and a large observational study.. The role of colchicine may expand beyond gout flare prevention to patients with existing CVD. The renal benefit of ULT among patients with gout remains unclear. SGLT-2 inhibitors may benefit diabetic patients who have gout as a comorbidity.

Topics: Allopurinol; Comorbidity; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Observational Studies as Topic; Symptom Flare Up

The treatment of gout with allopurinol is effective at reducing urate levels and the frequency of flares. Several observational studies have shown important reductions in mortality with allopurinol use, with wide variations in results. We undertook this review to assess the extent of bias in these studies, particularly time-related biases such as immortal time bias.. We searched the literature to identify all observational studies describing the effect of allopurinol use versus nonuse on all-cause mortality.. We identified 12 observational studies, of which 3 were affected by immortal time bias and 3 by immeasurable time bias, while the remaining 6 studies avoided these time-related biases. Reductions in all-cause mortality with allopurinol use were observed among the studies with immortal time bias, with a pooled hazard ratio (HR) of death associated with allopurinol of 0.71 (95% confidence interval [95% CI] 0.50-1.01), as well as in those with immeasurable time bias (pooled HR 0.62 [95% CI 0.56-0.67]). The 6 studies that avoided these biases demonstrated a null effect of allopurinol on mortality (pooled HR 0.99 [95% CI 0.87-1.11]), though the lack of an analysis based on treatment adherence may have attenuated the effect.. Observational studies are important to provide real-world data on medication effects. The observational studies showing significantly decreased mortality with allopurinol treatment cannot be used as evidence, however, mainly due to time-related biases that tend to greatly exaggerate the potential benefit of treatments. The ALL-HEART randomized trial, which is currently underway and evaluates the effect of adding allopurinol to usual care (compared to no added treatment), will provide reliable evidence on mortality.

Topics: Allopurinol; Bias; Cause of Death; Gout; Gout Suppressants; Humans; Hyperuricemia; Mortality; Observational Studies as Topic; Proportional Hazards Models; Time Factors; Uric Acid

The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with allopurinol. In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2000 and April 4, 2021, without any language restrictions. We did a systematic review and meta-analysis of included clinical trials to evaluate the cardiovascular safety of febuxostat compared to allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). From 240 potentially relevant citations, 224 papers were excluded; 16 studies were ultimately included in the analysis. Febuxostat had a better safety outcome compared with allopurinol，which was the composite of urgent coronary revascularization (OR: 0.84, 95% CI: 0.77-0.90, p < .0001) and stroke (OR: 0.87, 95% CI: 0.79-0.97, p = .009). However, that difference was not found in nonfatal myocardial infarction (OR: 0.99, 95% CI: 0.80-1.22, p = .91), cardiovascular related mortality (OR: 0.98, 95% CI: 0.69-1.38, p = .89) and all-cause mortality (OR: 0.93, 95% CI: 0.75-1.15, p = .52). No significant differences in cardiovascular related mortality and all-cause mortality were observed across any subgroup. This meta-analysis adds new evidence regarding the cardiovascular safety of febuxostat in patients. Initiation of febuxostat in patients was not associated with an increased risk of death or serious cardiovascular related adverse events compared with allopurinol.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Myocardial Infarction

Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014.  OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout.. We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020.. We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults.. We used standard methodological procedures expected by Cochrane.. We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded. Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Randomized Controlled Trials as Topic; Thioglycolates; Triazoles; Urate Oxidase

Hyperuricaemia is characterised by a high level of urate in the blood. The crystallisation of urate is considered a critical risk factor for the development of gout. Allopurinol and febuxostat have been commonly used medications to decrease the circulating urate levels. However, the use of these drugs is associated with undesired side effects. Therefore, the development of a new active, safety anti-hyperuricaemic and anti-inflammatory drug could be useful in gout therapy and is highly justified. Natural products have become a source of new pharmaceuticals due to their strong efficacy with less side effects, which relies on the comprising of complex bioactive compounds. There are a growing number of studies purporting decreasing serum urate with traditional medicines. This article was aimed to review these studies and identify which extracts promote urate reduction, along with their different mechanisms.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Asteraceae; Biological Products; Double-Blind Method; Gout; Humans; Hyperuricemia; Inflammation; Mice; Placebos; Plant Extracts; Randomized Controlled Trials as Topic; Risk Factors; Tabebuia; Uric Acid; Xanthine Oxidase

Uric acid, the metabolic mediator of gout and urate renal stones, is associated with increased cardiovascular risk burden. Hyperuricemia is an old emerging metabolic disorder, and interaction among uric acid and cardiovascular diseases has been clearly described. Several illness including hypertension, myocardial infarction, metabolic syndrome, and heart failure, are related with uric acid levels increase. In this review, we will discuss the pathophysiology of hyperuricemia and describe the biological plausibility for this metabolite to participate in the pathogenesis of cardiovascular disorders. In particular, we will focus on the implications of hyperuricemia in the onset and progression of heart failure, paying special attention to the pathophysiology and the possible clinical implications. We will conclude by discussing the effects of lowering plasma uric acid concentration on the prognosis of heart failure by reviewing most of available data on the different classes of drugs directly or indirectly involved in the hyperuricemia management.

Topics: Angiotensin II Type 1 Receptor Blockers; Cardiovascular Diseases; Disease Progression; Gout; Gout Suppressants; Heart Failure; Humans; Hyperuricemia; Protease Inhibitors; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Uric Acid; Xanthine Oxidase

The management of gout consists of urate-lowering therapy and acute and chronic anti-inflammatory drugs. Allopurinol, a xanthine oxidase inhibitor, is the primary urate-lowering therapy employed for decades. Recent studies suggest cardiovascular disease and mortality, chronic kidney disease, prostate cancer, and manic symptoms are reduced in patients with gout treated with allopurinol. These findings support that allopurinol contributes to a variety of beneficial effects beyond urate lowering. This manuscript reviews the analgesic and anti-inflammatory properties of allopurinol, which are rarely discussed. Several mechanisms are suggested to confer these benefits including accumulation of adenosine and inhibitory effects of allopurinol on reactive oxygen species, tumor necrosis factor- α, nuclear factor kappa-light-chain-enhancer of activated B cells, and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. Also, allopurinol blocks the stimulating effects of thioredoxin-interacting protein and interacts directly with the redox-active domain of thioredoxin as a negative regulator, decreasing NLRP3 activation. The importance of allopurinol's analgesic and anti-inflammatory properties requires further study and the implications to patient care better understood.

Topics: Allopurinol; Analgesics; Anti-Inflammatory Agents; Enzyme Inhibitors; Free Radical Scavengers; Gout; Gout Suppressants; Humans; Oxidative Stress; Uric Acid; Xanthine Oxidase

This review discusses the findings of recently published translational research studies that have the potential to directly impact on the management of gout patients.. Recent research suggests that treat-to-target urate-lowering treatment (ULT) alongside individualized education about gout, and shared decision making results in excellent adherence with ULT and prevents gout flares in the long term. Such interventions should preferentially be delivered face-to-face rather than remotely. The recently published CARES study raises the possibility that febuxostat increases the risk of death in people with preexisting major cardiovascular diseases, and, allopurinol should remain the first-choice ULT. There is paucity of data on the dosing of ULT for managing hyperuricaemia in gout patients with chronic kidney disease. However, recent research suggests that the dose of allopurinol can be gradually increased to above the conventional renal dose in people with chronic kidney disease without allopurinol hypersensitivity syndrome. However, additional larger studies are needed in this field.. In summary, long-term treat-to-target ULT prevents gout flares and improves quality of life. Given the recent safety concerns, gradually up-titrated allopurinol remains the first-line urate-lowering drug.

Topics: Allopurinol; Disease Management; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Quality of Life

While there is consensus on starting urate-lowering therapy (ULT) in cases of symptomatic hyperuricemia, the frequent condition of asymptomatic hyperuricemia (AH) remains a challenge due to differences in the findings of studies that have addressed the issue. Uric acid has anti-oxidant properties, but high levels predispose to gout and may play a role in metabolic syndrome. We systematically evaluated randomized controlled trials (RCTs) addressing ULT in patients with AH, to assess the current evidence. We found broad heterogeneity among the studies (13 RCTs), in terms of study design and population, making findings challenging to interpret and generalize; hard end-points were not assessed. Allopurinol is often prescribed for AH despite the fact that its use is not backed by conclusive evidence from prospective RCTs, nor is it recommended by the guidelines. Its potential benefits, in terms of absolute risk reduction, must be weighed against its potential for harm since it can trigger severe adverse hypersensitivity reactions, sometimes even fatal. RCTs with hard end-points are needed to assess the risk/benefit of lowering uric acid in subjects with AH, particularly as secondary prevention for cardiovascular risk and in patients with different degrees of renal disease. To date, particularly after the result from the CARES trial, preventive treatment of asymptomatic and non-severe hyperuricemia is not recommended.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid

Topics: Allopurinol; Gout; Humans; Hyperuricemia

Allopurinol, a first line urate-lowering therapy, has been associated with serious cutaneous reactions that have a high mortality. A number of risk factors for these serious adverse reactions have been identified including ethnicity, HLA-B∗5801 genotype, kidney impairment, allopurinol starting dose, and concomitant diuretic use. There is a complex interplay between these risk factors, which may (albeit rarely) lead to allopurinol-related serious adverse events. Although oxypurinol, the active metabolite of allopurinol, has been implicated, there is no defined drug concentration at which the reaction will occur. There is no specific treatment other than the cessation of allopurinol and supportive care. Whether hemodialysis, which rapidly removes oxypurinol, improves outcomes remains to be determined. Strategies to help reduce this risk are therefore important, which includes screening for HLA-B∗5801 in high-risk individuals, commencing allopurinol at low dose, and educating patients about the signs and symptoms of severe cutaneous adverse reactions, and what to do if they occur.

Topics: Allopurinol; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Oxypurinol

Inflammation induced by urate deposition in joints causes gout. Healthy individuals maintain serum levels of urate by balancing urate production/excretion, whereas a production/excretion imbalance increases urate levels. Hyperuricemia is diagnosed when the serum urate level is continuously above 7 mg/dl as the solubility limit, and urate accumulates in the kidneys and joints. Because hyperuricemia increases the risk of gout, therapies aim to eliminate urate deposition to prevent gouty arthritis and kidney injury.. This review discusses the mechanism underlying hyperuricemia with respect to urate production and urate transport, along with urate-lowering therapeutics, including urate synthesis inhibitors, uricolytic enzymes, and uricosuric agents. The authors asses published data on relevant commercial therapy development projects and clinical trials.. Available treatment options for hyperuricemia are limited. Allopurinol, a urate synthesis inhibitor, is generally administered at a reduced dosage to patients with renal impairment. Some URAT1 inhibitors have an unfavorable side effect profile. A promising strategy for treatment is the use of uricosuric agents that inhibit transporters (e.g. URAT1, URATv1/GLUT9, OAT10) which reabsorb urate from the urine.

Topics: Allopurinol; Arthritis, Gouty; Drug Discovery; Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid

Hyperuricemia (HUA) and gout are considerable public health problems because of their increasing incidence and interactions with other diseases. We aimed to evaluate the efficacy and safety of urate-lowering therapies (ULTs) for patients.. A systematic literature review was conducted, and a network meta-analysis was performed on the included studies using the Markov Chain Monte Carlo simulation method and a Bayesian statistical framework. We calculated surface under the cumulative ranking curve (SUCRA) values and performed clustered ranking to combine the efficacy and safety results.. Twenty-two randomized controlled studies were identified for the efficacy analysis, and 20 studies were identified for the safety analysis. Compared with the placebo, the ULTs were efficient and safe. Febuxostat 120 mg/d and allopurinol 200 mg/d had the highest SUCRA scores for efficacy and safety, respectively. Clustered ranking results showed that febuxostat 120 mg/d was the best in terms of efficacy and safety, topiroxostat 120/160 mg/d was similar to febuxostat 80 mg/d in terms of efficacy but safer, and allopurinol was not inferior to topiroxostat.. Febuxostat had the best efficacy and safety results among the tested agents, and topiroxostat and allopurinol appeared to have fewer adverse events.

Topics: Allopurinol; Bayes Theorem; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Uric Acid

Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia and gout. Allopurinol and febuxostat are the most commonly used urate-lowering therapies with established safety and efficacy in CKD patients. The objective of the systematic review is to assess the long-term renal outcomes of allopurinol compared with febuxostat in patients with hyperuricemia and CKD or kidney transplantation. PubMed MEDLINE, Embase, Web of Science, Scopus, and Cochrane CENTRAL databases were searched from inception to December 2019 using the key terms "allopurinol," "febuxostat," "xanthine oxidase inhibitors," "gout suppressants," "hyperuricemia," "gout," "chronic renal insufficiency," and "kidney transplantation." Studies with follow-up duration ≥ 12 months were included. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Three retrospective observational studies with follow-up duration ranging from 1 to 5 years were reviewed. Febuxostat patients had a significantly higher estimated glomerular filtration rate, reduced risk for renal disease progression, and reduced serum uric acid levels compared with allopurinol patients. All studies had a serious risk of bias. Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD based on evidence from small long-term retrospective studies with serious risk of bias. More methodologically rigorous studies are needed to determine the clinical applicability of these results.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Uric Acid

The incidence and prevalence of gout have increased, as have comorbid obesity, diabetes mellitus, hypertension, chronic kidney and cardiovascular disease. Gout is now the commonest type of inflammatory arthritis despite availability of safe, effective and potentially 'curative' urate-lowering drugs. Modern imaging studies show that gout is a chronic inflammatory crystal deposition disorder even at the first acute attack and they illuminate the need to eliminate urate crystals by continuing reduction of the serum urate below its solubility threshold. Clinical outcomes, adherence to therapy and quality of gout care in primary care and hospital practice can be greatly improved by better use of allopurinol and flare prophylaxis, greater patient engagement, education and follow-up, and by nurse-led models of care that employ a 'treat-to-target' principle (SUA< 360 or 300µmol/l). Advances in understanding the physiology and genetic control of urate transport in the kidney and gut have led to novel, more selective uricosuric drugs, and basic research on mediators of urate crystal-induced inflammation has pointed to alternative therapeutic targets for treating and preventing gout flares. Current guidelines for the management of gout and indications for the use of some more recently introduced drugs; febuxostat, lesinurad, pegloticase and interleukin-1 antagonists are also briefly reviewed.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Uric Acid

Uric acid is the final byproduct of purine metabolism. The loss of the enzyme that hydrolyzes uric acid to allantoin was lost, leading to a decrease in uric acid excretion and its further accumulation. The buildup of uric acid leads to damage in different organ systems, including the cardiovascular system. With the increasing burden of cardiovascular disease worldwide, a growing body of evidence has addressed the relationship between urate, cardiovascular outcomes, and gout medication cardiovascular safety.. The treatment of gout reduces joint damage and it can also lessen CV morbidity. Allopurinol shows CV safety profile when compared to other ULTs. Evidence supporting CV safety with the use of colchicine and IL-1 agents is promising and research needs to be conducted to further assess this outcome.

Topics: Allopurinol; Animals; Cardiovascular Diseases; Colchicine; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Uric Acid

Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout.. Herein, patents from 2015 to 2020 are discussed to disclose the synthetic, as well as natural compounds, claimed to inhibit XO enzyme. The article also presents the last five years of clinical progression of some prominent XO inhibitors.. There has been considerable creativity in the discovery of novel XO inhibitors in the last five years that falls outside the purine scaffold. Along with the evaluation of synthetic compounds, natural compounds can also be an area of interest for the discovery of novel XO inhibitors. Based on the patent literature of last five years, we can expect a burst of novel alternate compounds in the near future which could have the ability to reduce the uric acid level, by inhibiting XO enzyme in patients, which at the moment are striving hard to fight against the dreadful disease condition like gout.

Topics: Animals; Drug Development; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Patents as Topic; Reactive Oxygen Species; Uric Acid; Xanthine Oxidase

Gout is caused by monosodium urate crystal deposition in joints and tissues. Risk factors include male sex; obesity; hypertension; alcohol intake; diuretic use; a diet rich in meat and seafood; chronic kidney disease; a diet heavy in fructose-rich food and beverages; being a member of certain ethnic groups, including Taiwanese, Pacific Islander, and New Zealand Maori; and living in high-income countries. Gout is characterized by swelling, pain, or tenderness in a peripheral joint or bursa, including the development of a tophus. Diagnosis of gout can be made using several validated clinical prediction rules. Arthrocentesis should be performed when suspicion for an underlying septic joint is present; synovial fluid or tophus analysis should be performed if the diagnosis is uncertain. Colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids relieve pain in adults with acute gout episodes. Indications for long-term urate-lowering therapy include chronic kidney disease, two or more flare-ups per year, urolithiasis, the presence of tophus, chronic gouty arthritis, and joint damage. Allopurinol and febuxostat are used to prevent flare-ups, although febuxostat is associated with an increase in all-cause and cardiovascular mortality and is therefore not routinely recommended.

Topics: Adrenal Cortex Hormones; Allopurinol; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Obesity; Risk Factors; Sex Factors; Uric Acid

Gout is the most common inflammatory arthritis in the USA, affecting about 4% of all adults. The American College of Rheumatology (ACR) released a new guideline in 2020 to help with the management of gout. This guideline serves as an update to the previous set of guidelines which the ACR published in 2012. The purpose of this review is to compare the 2012 ACR gout guidelines to the newly released 2020 ACR gout guidelines.. There are many similarities between the two guidelines, and also several key differences. The 2020 guidelines assist in the clinical management of gout by healthcare providers. Additionally, the new guidelines utilize newer literature to help create an evidence-based approach to the treatment for gout. We discuss the methodological approach to each guideline (RAND versus GRADE), as well as the final recommendations for gout flare treatment, use of imaging, urate-lowering therapy, lifestyle changes, and genetic testing prior to initiation of allopurinol in each guideline, as well as lingering issues that the 2020 guidelines have not addressed. We dissect both the 2012 and 2020 ACR gout guidelines to summarize the key similarities and differences between the two as well as discuss how the authors came to the recommendations that they did for each set of guidelines.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Practice Guidelines as Topic; Rheumatology; Symptom Flare Up; United States

We conducted a meta-analysis to compare the febuxostat and allopurinol in hyperuricemic patients diagnosed with or without Gout.. We searched the Pubmed, Cochrane and Embase electronic databases to identify the studies concerning febuxostat versus allopurinol in treatment of hyperuricemic subjects and/or gout updated to May, 2020. After rigorous evaluation on quality, the data was extracted from included publications.. A total of 10 articles involving 6989 subjects were included, with 4841 receiving febuxostat and 2148 using allopurinol. The pooled analysis showed that the febuxostat group (40, 80, or 120 mg QD) was greater in reducing serum urate levels than the allopurinol group (200 or 300 mg) (RR=1.56, 95% CI=1.37-1.78, P<0.00001). In addition, daily dosing of febuxostat 80 mg had greater efficacy to that of febuxostat 40 mg (RR=1.47, 95% CI=1.34-1.60, P<0.00001), and febuxostat 120 mg/day was associated with lower serum urate levels versus febuxostat 80 mg/day (RR=1.08, 95% CI=1.02-1.13, P=0.004). In terms of the adverse events, the pooling overall adverse events data did achieve advantage in the febuxostat group (RR=0.96, 95% CI=0.92-1.00, P=0.04). While, liver function test abnormalitie , diarrhea, skin rashes, musculoskeletal and connective tissue disorders, gastrointestinal disorders, headaches, the statistical significance between the two groups fail to be achieved (P≥0.05).. Febuxostat was superior in reducing the serum urate levels of hyperuricemic patients, while with an acceptable tolerability profile than allopurinol. Moreover, our result suggested that dose titration to febuxostat 120 mg daily was superior to other daily dosing with regard to urate-lowering efficacy.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Treatment Outcome

Gout, a debilitating inflammatory arthritis, currently affects more than 9 million Americans. Hyperuricemia, the laboratory abnormality associated with the development of gout, also occurs in a significant number of patients with chronic kidney disease (CKD), a condition that affects approximately 14% of the US population. Several recent studies have attempted to provide a definitive link between the presence of hyperuricemia and progression of CKD; however, the treatment of asymptomatic hyperuricemia in CKD is not supported by recent randomized controlled trials. The pharmacology of acute gout flares and urate lowering is complicated in patients who also have evidence of CKD, primarily because of an increased risk of medication toxicity. Recipients of kidney transplants are particularly at risk of debilitating gout and medication toxicity. We review the available data linking CKD, gout, and hyperuricemia, providing practice guidelines on managing gout in CKD patients and kidney transplant recipients. We advocate for much greater involvement of nephrologists in the management of gout in renal patients.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia

This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management. New imaging tools are available, including US with key features and dual-energy CT rendering it able to reveal deposits of urate crystals. These deposits are now included in new diagnostic and classification criteria. Overall, half of the patients with gout are readily treated with allopurinol, the recommended xanthine oxidase inhibitor (XOI), with prophylaxis for flares with low-dose daily colchicine. The main management issues are related to patient adherence, because gout patients have the lowest rate of medication possession ratio at 1 year, but they also include clinical inertia by physicians, meaning XOI dosage is not titrated according to regular serum uric acid level measurements for targeting serum uric acid levels for uncomplicated (6.0 mg/dl) and complicated gout, or the British Society for Rheumatology recommended target (5.0 mg/dl). Difficult-to-treat gout encompasses polyarticular flares, and mostly patients with comorbidities, renal or heart failure, leading to contraindications or side effects of standard-of-care drugs (colchicine, NSAIDs, oral steroids) for flares; and tophaceous and/or destructive arthropathies, leading to switching between XOIs (febuxostat) or to combining XOI and uricosurics.

Topics: Allopurinol; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid; Xanthine Oxidase

Despite many effective treatments for gout, its management remains a challenge internationally. Options for optimizing gout management may differ in different practice sizes and settings. Gout incidence is rising and it continues to be associated with increased mortality. Education of patients and medical providers is essential, and newer gout medications need to be used in the most appropriate ways for cost-effective therapy. Special consideration needs to be given to such populations as the elderly and those with renal and cardiovascular disease in gout management. New agents are in development, which may add to the armamentarium for gout management.

Topics: Acetamides; Allopurinol; Antibodies, Monoclonal, Humanized; Colchicine; Diet Therapy; Febuxostat; Gout; Gout Suppressants; Humans; Medication Adherence; Patient Education as Topic; Phenylacetates; Polyethylene Glycols; Quality of Health Care; Rheumatology; Thioglycolates; Triazoles; Urate Oxidase; Uric Acid

Many novel genetic associations in the field of hyperuricaemia and gout have been described recently. This review discusses advances in gout genetics and their potential clinical applications.. Genome-wide association studies have identified approximately 30 serum urate-associated loci, some of which represent targets for drug development in gout. Some genes implicated in initiating the inflammatory response to deposited crystals in gout flares have also been described. In addition, genetic studies have been used to understand the link between hyperuricaemia and other comorbidities, particularly cardiometabolic diseases. ABCG2 has been established as a key genetic determinant in the onset of gout, and plays a role in the progression and severity of disease. Recent pharmacogenetic studies have also demonstrated the association between ABCG2 and poor response to allopurinol, and the link between HLA-B58:01 genotype and adverse drug reactions to allopurinol.. Advances in gout genetics have provided important molecular insights into disease pathogenesis, better characterized the pharmacogenetics of allopurinol, and raised the possibility of using genetic testing to provide personalized treatment for patients. Prospective studies are now needed to clarify whether genetic testing in gout provides further benefit when added to established clinical management.

Topics: Allopurinol; Disease Progression; Genome-Wide Association Study; Gout; Gout Suppressants; HLA-B Antigens; Humans; Uric Acid

The safety of newer xanthine oxidase inhibitor febuxostat compared to allopurinol remains unclear. To compare the risks of allopurinol hypersensitivity and febuxostat hypersensitivity and cardiovascular diseases (CVDs) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012-2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users. The overall incidence of febuxostat hypersensitivity was significantly lower than allopurinol hypersensitivity (0.2 vs. 2.7 per 1,000 new users; P < 0.001). There were 33 allopurinol-hypersensitivity reactions (including 18 severe cutaneous adverse drug reactions), and only one patient developed febuxostat-maculopapular exanthema. Moreover, febuxostat did not statistically increase the risk of CVD (hazard ratio (HR), 1.16; P = 0.152) and related death (HR, 1.49; P = 0.496) compared to allopurinol. The result of the meta-analysis also showed a consistent result. In conclusion, the incidence and severity of febuxostat-hypersensitivity are lower than with allopurinol. Febuxostat did not show an increased risk of CVD and related death.

Topics: Aged; Allopurinol; Asian People; Cardiovascular Diseases; Cohort Studies; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Febuxostat; Gout; Gout Suppressants; Humans; Middle Aged; Taiwan

Gout is a disease characterized by abnormal metabolism of the uric acid, leading to undesired buildup of monosodium urate crystals affecting mainly the first metatarsal-phalangeal joint of the foot and less commonly other joints or the soft tissues of the body. The prevalence of the disease increases with age, and it is statistically more observed in men than in women.We present the case of a 62-year-old male patient diagnosed as having gout 20 years ago. He came to the clinic with a nasal hump and a mass growing in his nose for the last 3 years, presenting as a nasal obstruction and facial deformity. Although the patient was treated with allopurinol and nonsteroidal anti-inflammatory drugs, surgical treatment was deemed necessary, and the patient was taken to receive a surgical resection of the nasal mass. The follow-up histopathology observation revealed deposits of urate crystals surrounded by a granulomatous inflammation. This confirmed the diagnosis-gouty tophi in the nose. In the follow-up period after the surgery, the patient reported overall improved breathing and aesthetic results.Tophi can be found in atypical locations, which increases morbidities and deformities caused by the disease. We report on this peculiar case of tophaceus gout as it is-a rare manifestation of the disease with tophi located in the nasal region.

Topics: Allopurinol; Biopsy, Needle; Gout; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Cavity; Nasal Obstruction; Nose; Prognosis; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome; Uric Acid

Cardiovascular disease affects more than 90 million Americans. Recent studies support an increased cardiovascular disease risk in inflammatory conditions, such as gout. Increased serum urate levels, or hyperuricemia, are a precursor to gout. Data from meta-analyses have shown hyperuricemia to be linked to hypertension and coronary heart disease. Similarly, gout has been associated with an increased risk of myocardial infarction, cerebrovascular accidents, and death from cardiovascular disease in randomized clinical trials. Urate-lowering therapy reduces serum urate and may decrease systemic inflammation, generation of oxidative species, and reverses endothelial dysfunction through hyperuricemia-dependent or hyperuricemia-independent pathways. Cardioprotective benefits of allopurinol, a first-line agent for the treatment of gout, have been demonstrated to potentially prevent myocardial infarction, stroke, atrial fibrillation, and other cardiovascular diseases in observational studies in select populations. Randomized controlled trials (RCTs) have also examined the role of newer urate-lowering therapies, such as febuxostat and lesinurad, and their risk of cardiovascular-specific mortality in comparison to allopurinol. A large post-marketing study of febuxostat vs. allopurinol showed higher all-cause and cardiovascular-specific mortality in the febuxostat group than in the allopurinol group; a major study limitation was that large numbers of patients were lost to follow-up or discontinued treatment. RCTs are required to assess the comparative effectiveness of urate-lowering therapies, validate findings of observational studies, and to determine which subgroup populations of gout are most likely to benefit from appropriate long-term urate-lowering therapy. This review examines the data for increased cardiovascular disease in gout and potential underlying mechanisms (including hyperuricemia, inflammation, endothelial dysfunction, oxidative stress) and the effect of urate-lowering therapy on cardiovascular disease.

Topics: Allopurinol; Anti-Inflammatory Agents; Cardiovascular Diseases; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Thioglycolates; Treatment Outcome; Triazoles; Uric Acid

A systematic review and meta-analysis were conducted to investigate the associations of hyperuricemia, gout, and uric acid (UA)-lowering therapy with the risk of fractures.. Electronic searches on PubMed, the Cochrane Library, and Embase were conducted from inception to January 2, 2019. Observational studies assessing the effects of hyperuricemia, gout, and UA-lowering therapy on fractures were included in the meta-analysis. Summary risk estimates with 95% confidence intervals (CI) were calculated by a random-effects model.. A total of 14 eligible studies with 909 803 participants and 64 047 incident fractures were included. The results suggested that hyperuricemia and gout are not associated with any type of fracture (relative risk [RR], 0.98, 95% CI 0.85-1.11; P = 0.71) or osteoporotic fractures (RR, 1.02, 95% CI 0.90-1.14; P = 0.79). Further analysis indicated that hyperuricemia is associated with a lower risk of fractures (RR, 0.80, 95% CI 0.66-0.96; P = 0.02) but not with osteoporotic fractures (RR, 0.84, 95% CI 0.68-1.03; P = 0.10). However, gout is associated with an increased risk of fractures (RR, 1.17, 95% CI 1.04-1.31; P = 0.007) as well as osteoporotic fractures (RR, 1.13, 95% CI 1.00-1.26; P = 0.045). Furthermore, no significant association of UA-lowering therapy with the risk of fractures was found compared with the placebo (RR, 0.88, 95% CI 0.76-1.03; P = 0.11). Evidence supporting a non-linear association between serum UA levels and fractures was found (P < 0.001 for non-linearity), which revealed a U-shaped curve.. Our meta-analysis revealed that hyperuricemia was associated with lower risk for any type fracture but not associated with osteoporotic fractures; however, gout was associated with an increased risk of any type fracture as well as osteoporotic fractures. Notably, a U-shaped relationship may exist between the serum UA level and fractures. The associations observed in our study may be due to reasons other than causality.

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Observational Studies as Topic; Osteoporotic Fractures; Patient Safety; Risk Assessment

Urate-lowering therapy (ULT) is the cornerstone of gout management, which is a widespread chronic illness characterized by hyperuricemia, arthropathy, tophus development, and urolithiasis. Since asymptomatic increased serum urate levels are associated with a higher risk of cardiovascular, renal and metabolic disorders, a larger use of ULTs in the general population is expected in the near future.. This review will focus on the safety and tolerability profile of the available urate-lowering drugs: xanthine oxidase inhibitors (XOIs), uricosuric agents and injectable uricases.. Older drugs for ULT like allopurinol are well studied and extensively described from typical adverse effects (mild skin rash) to unusual fatal reactions, while febuxostat seems to be overall well tolerated. More evidence is required to define the safety profile of topiroxostat, arhalofenate, tranilast, and sulfinpyrazone. Furthermore, there are some unanswered questions about the pharmacological interactions of probenecid and the hepatotoxicity of benzbromarone. Despite a limited use in clinical practice, combination therapy with lesinurad or verinurad and XOI is not frequently accompanied by side effects. Rasburicase and pegloticase are usually well tolerated with some specific exceptions. Before prescribing UL drugs, physicians should take into account their safety profile tailoring the treatment on the patient characteristics.

Topics: Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Uric Acid; Uricosuric Agents; Xanthine Oxidase

We aimed to assess the relative efficacy and safety of once-daily administration of lesinurad in combination with xanthine oxidase inhibitor (XOI) in hyperuricemic patients with gout.. A Bayesian random-effects network meta-analysis was performed to combine the direct and indirect evidence from randomized controlled trials (RCTs) for evaluating the efficacy and safety of lesinurad 200 mg + XOI, lesinurad 400 mg + XOI, and XOI monotherapy in hyperuricemic patients with gout.. Three RCTs including a total of 1,537 patients fulfilled the inclusion criteria. The number of patients who had achieved a target serum uric acid (sUA) level was significantly higher in the lesinurad 40 mg + XOI and lesinurad 200 mg + XOI groups than in the XOI monotherapy group (R 4.55, 95% credible interval (CrI) 2.13 - 9.81 and OR 2.78, 95% CrI 1.28 - 5.71, respectively). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that lesinurad 400 mg + XOI was more likely to achieve the best target sUA level (SUCRA = 0.968), followed by lesinurad 200 mg + XOI (SUCRA = 0.526), and XOI (SUCRA = 0.006). The frequency of treatment-emergent adverse events (TEAEs) in the XOI group was significantly lower than that in the lesinurad 400 mg + XOI group (OR 0.59, 95% CrI 0.39 - 0.90).. Lesinurad 200 mg + XOI and lesinurad 400 mg + XOI were more effective than XOI for hyperuricemic patients with gout, but lesinurad 400 mg + XOI had a significant risk of TEAE development.

Topics: Bayes Theorem; Drug Therapy, Combination; Gout; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thioglycolates; Triazoles; Uric Acid; Xanthine Oxidase

The effect of urate lowering treatment (ULT) on cardiovascular (CV) risk and mortality in gout has been a topic of interest. This review discusses the CV effect of ULT and comparative CV safety among ULT agents.. The mechanism linking gout with CV risk is not fully understood but seems multifactorial involving hyperuricemia, xanthine oxidase (XO), oxidative stress, and chronic inflammation. Conflicting data exist regarding CV benefits of ULT in adults with and without hyperuricemia. Although meta-analyses on randomized controlled trials (RCTs) suggest CV benefits with allopurinol, few high-quality RCTs have examined the CV effect of ULT among patients with hyperuricemia or gout. The recent CARES trial adds new information on comparative CV safety between two XO inhibitors (XOIs), febuxostat and allopurinol, in patients with gout. It remains unclear whether ULT reduces CV risk in patients with gout or hyperuricemia. Comparative CV safety studies of XOIs suggest that additional mechanisms beyond urate-lowering effect or XO inhibition are likely involved in CV risk modification in patients with gout. Ongoing RCTs of ULT may be able to further determine the effect of ULT on CV risk.

Topics: Allopurinol; Cardiovascular Diseases; Endothelium; Febuxostat; Gout; Gout Suppressants; Heart Failure; Humans; Hypertension; Hyperuricemia; Myocardial Infarction; Probenecid; Risk; Stroke; Uricosuric Agents; Xanthine Oxidase

Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia.. PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included.. Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia.. PROSPERO(CRD42018091657).

Topics: Aged; Allopurinol; Asymptomatic Diseases; Biomarkers; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

In the management of chronic gout, a large proportion of patients need long-term management with urate lowering therapy (ULT). This study reviews medication adherence to ULT and summarizes factors associated with adherence.. We performed a systematic literature search for studies on adherence to ULT among gout patients in PubMed, Embase, CINAHL, and PsycINFO. We conducted meta-analysis, with a random effect model, for the studies reporting the proportion of patients considered adherent to at least 80% of prescribed medication or time taken. We explored potential sources of heterogeneity, including geographic area and measure of adherence. Narrative summaries were made for data on adherence assessed/defined by Medication Event Monitoring System (MEMS)/pill-count or patient-reported, occurrence of a gap in therapy ≥30 days (non-persistence), and factors associated with adherence.. Of the 24 studies, 16 assessed adherence using prescription/claims data, two by the MEMS or pill count, and six by patient-reported data. The pooled proportion of adherent patients (n = 13) was 46% (95% CI: 41-51); 45% across studies conducted in the USA (n = 8) and 48% in other countries (n = 5). Adherence assessed by MEMS/pill count and patient-reported was much higher than by studies using prescription/claims data. Non-persistence (n = 6) ranged from 54% to 87%. Factors associated with adherence were investigated in 18 studies. Strong evidence for a positive association with older age, more comorbidities, and the presence of diabetes or hypertension was found.. Medication adherence to ULT among gout patients was poor. Better insight into reasons and consequences or poor adherence is needed.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Medication Adherence

Allopurinol hypersensitivity syndrome (AHS) is a severe and sometimes life-threatening adverse drug reaction. Although AHS is rare, the number of patients with gout requiring allopurinol is high, and there are sufficient overall cases of AHS to warrant consideration of preventive measures. Most cases occur within 8-9 weeks of commencing allopurinol, and good patient education at initiation may lead to rapid drug cessation at onset of symptoms. Pretreatment testing for HLA-B*5801 and avoidance of allopurinol when positive reduces the risk of AHS and is cost-effective in some ethnic groups. A low starting allopurinol dose may reduce AHS risk, but the relationship between maintenance dose and AHS is more controversial. Chronic kidney disease increases AHS risk, but slowly increasing the allopurinol dose in chronic kidney disease has not been associated with AHS. Alternative newer treatments are available for patients at risk of AHS, but similar adverse reactions can also occur with these.

Topics: Allopurinol; Dose-Response Relationship, Drug; Drug Hypersensitivity; Gout; Gout Suppressants; Humans

ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis.. Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied. In patients with evidence of adherence to allopurinol therapy (plasma oxypurinol >20 μmol/l), good response was defined as serum urate <6 mg/dl on allopurinol ⩽300 mg/day and poor response as serum urate ⩾ 6 mg/dl despite allopurinol >300 mg/day. Association of rs2231142 and rs10011796 with poor response was tested in logistic regression models that included age, sex, BMI, ethnicity and estimated glomerular filtration rate. Results from the LASSO study and a subset of participants in the Genetics of Gout in Aotearoa New Zealand study (n = 296, including 264 from a previously published report) were combined by meta-analysis.. There was evidence for association of rs2231142 with allopurinol response [odds ratio (OR) = 2.35, P = 7.3 × 10-4] but not for rs10011796 (OR = 1.21, P = 0.33) in the LASSO cohort using an adjusted logistic regression model. Meta-analysis provided evidence of a significant association of rs2231142 with allopurinol response (OR = 2.43, P = 6.2 × 10-7), but not rs10011796 (OR = 1.06, P = 0.69).. This study has confirmed the significant association of ABCG2 rs2231142 with poor response to allopurinol.

Topics: Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; DNA; Genetic Predisposition to Disease; Genotype; Gout; Gout Suppressants; Humans; Neoplasm Proteins; Polymorphism, Single Nucleotide

Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI. Our objective is to compare the incidence of major adverse cardiovascular events (MACE), mortality, total (TCE) and specific CV events in randomized controlled trials (RCTs) testing XOI against placebo or no treatment.. PubMed, EMBASE, Web of Science, Cochrane Central, Lilacs databases were searched from inception to Dec 30 2016, along with hand searching. RCTs including exclusively adult individuals, lasting ≥ 4 weeks, with no language restriction, were eligible. Independent paired researchers selected studies and extracted data. Considering the expected rarity of events, Peto and DerSimonian/Laird odds ratios (OR), the latter in case of heterogeneity, were used for analysis. Random-effects meta-regression was used to explore heterogeneity.. Purine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (> 300 mg/day) may be associated with loss of CV protection.

Topics: Cardiovascular Diseases; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Incidence; Odds Ratio; Protective Factors; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Xanthine Oxidase

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are mucocutaneous hypersensitivity reactions, usually to drugs or their metabolites. TEN is the most severe involving greater than 30% of the total body surface area (TBSA). Management of these patients usually benefits from a large multidisciplinary team for both wound and medical management. Treatment of these patients varies between centers and physicians and there is lack of a standardized treatment protocol in the medical literature.. To review the literature and complete a retrospective review of patients treated at Vancouver General Hospital over a 11-year period.. A retrospective chart review of all patients diagnosed with SJS/TEN and treated at Vancouver General Hospital from 2001 to 2011 was completed. Data collected include patient demographics, time to transfer to a burn center, SCORTEN calculation, suspected cause of TEN, %TBSA involved, length of stay in hospital and ICU, medications, dressings, infections/cultures, fluids, mucosal involvement, teams involved, associated complications, morbidity and mortality. Data is reported quantitatively.. A total of 67 patients were identified (28 SJS, 21 SJS/TEN overlap, 18 TEN). In SJS/TEN overlap and TEN patients, oral mucosa and trunk were the primary sites involved. SCORTEN calculations were highest in the TEN group. Plastic surgery was consulted in 53% of TEN cases, 52% of SJS/TEN cases and 25% of SJS cases. Patients were admitted to a burn unit in 74% of TEN cases, 57% of TEN/SJS cases and 21% of SJS cases. Time from symptoms to diagnosis and transfer to a burn unit was highest for TEN patients. Time from presentation to diagnosis was highest in SJS/TEN overlap. Triggers were identified in 67-82% of cases. Treatment varied widely. Patients were treated conservatively, with steroids, IVIg, and cyclosporine alone or in combination. Observed mortality was higher than predicted by SCORTEN for patients treated with IVIg and lower for those treated with Cyclosporin. Dressings varied greatly and were often changed throughout a patients stay. Total mortality was 20.9% being the highest in the TEN group (35%).. SJS and TEN are a spectrum of severe mucocutaneous reactions that have unclear treatment recommendations within the literature and within our Level 1 hospital. Information gleaned from this research will help educate physicians involved in the treatment and management of patients with these diagnoses and has resulted in development of treatment guidelines in our hospital.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Bacterial Agents; Anticonvulsants; Bandages; British Columbia; Comorbidity; Cyclosporine; Dermatologic Agents; Dermatology; Diabetes Mellitus; Dietetics; Disease Management; Female; Gout; Gout Suppressants; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunologic Factors; Intensive Care Units; Length of Stay; Male; Middle Aged; Mouth Mucosa; Neoplasms; Patient Care Team; Retrospective Studies; Seizures; Stevens-Johnson Syndrome; Surgery, Plastic; Torso

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Risk Factors

Over the last 70 years, pharmacotherapy in gout with urate-lowering drugs has consisted of four drugs only: In 1952, a mild uricosuric probenecid became available, the xanthine oxidase inhibitor Allopurinol in 1964, and the latter became the most frequently used urate-lowering drug worldwide; in the Eurozone, the uricosuric benzbromarone was welcomed in 1977. Only in 2002, the potent non-purine xanthine oxidase inhibitor febuxostat was introduced. In many countries, uricosurics such as probenecid and benzbromarone have not been available up to now, and these days, the new uricosuric lesinurad is the first uricosuric that may be introduced in these countries, which is the reason for describing the position this novel uricosuric deserves in treating gout. Recent literature will be shortly reviewed, and the current proposed position for lesinurad will be given as an aid for clinicians.

Topics: Benzbromarone; Europe; Febuxostat; Gout; Humans; International Cooperation; Practice Guidelines as Topic; Probenecid; Rheumatology; Thioglycolates; Triazoles; Uricosuric Agents; Xanthine Oxidase

Gout is an increasingly common chronic disorder of urate crystal deposition that manifests as flares of acute inflammatory arthritis. Hyperuricaemia is a prerequisite and a fifth of both men and woman are hyperuricaemic. The prevalence of gout is much lower than the prevalence of hyperuricaemia for reasons that are not currently clear. Gout is more common in men than women prior to menopause due to the uricosuric effects of oestrogen, but after menopause the incidence of gout rises substantially in women. Co-morbidities are an important issue in gout, with cardiovascular disease, diabetes mellitus, obesity and chronic kidney disease all common in patients with gout. Environmental factors like diet affect the incidence of gout but there is little evidence to support an emphasis on diet in treating established gout. The diagnosis of gout is often made without the use of joint aspiration and validated diagnostic rules are available for both primary and secondary care as well as classification criteria for research use. The overarching principle of the management of gout with pharmacotherapy is the need to reduce serum urate levels to below a target of 0.30 mmol/L or 0.36 mmol/L depending on whether it is tophaceous or non-tophaceous respectively. The use of allopurinol has been researched extensively and newer strategies for safer effective dosing are now recommended. Newer agents have been introduced for the treatment of gout, including febuxostat and lesinurad. A number of important questions in the field are under current investigation.

Topics: Allopurinol; Chronic Disease; Comorbidity; Diet; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Probenecid; Thioglycolates; Triazoles; Uric Acid

Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider.

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Infectious; Arthrocentesis; Chondrocalcinosis; Diagnosis, Differential; Gout; Injections, Intra-Articular; Synovitis; Uricosuric Agents; Xanthine Oxidase

To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes.. Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors.. A total of 3084 citations were found, with 642 duplicates. After the primary screen, 35 studies were selected for review. Several trials did not report CV events. Six were not randomized controlled trials (RCTs). Four studies reported no events in either intervention arm while the other four had 40 events in the febuxostat group ( n = 3631) and 5 in allopurinol group ( n = 1154). Overall, the pooled analysis did not show a significant difference between the two [febuxostat vs allopurinol: relative risk (RR) 1.69 (95% CI 0.54, 5.34), P = 0.37]. CV events did not decrease over time. Comparing shorter studies (<52 weeks) to longer ones did not reveal any statistical differences. However, in long-term studies with febuxostat vs allopurinol, results were nearly significant, with more CVE occurring with febuxostat treatment. Comparing any ULT to placebo (eight studies, n = 2221 patients) did not demonstrate a significant difference in non-Anti-Platelet Trialists' Collaboration events [any ULT vs placebo: RR 1.47 (95% CI 0.49, 4.40), P = 0.49] or all-cause mortality [any ULT vs placebo: RR 1.45 (95% CI 0.35, 5.77), P = 0.60].. RCT data do not suggest differences in CV events among ULTs in gout. Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid.

Topics: Adult; Allopurinol; Arthritis, Gouty; Cardiovascular Diseases; Chronic Disease; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Polyethylene Glycols; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Urate Oxidase

Topics: Adult; Allopurinol; Drug Therapy, Combination; Enzyme Inhibitors; Febuxostat; Gout; Humans; Hyperuricemia; Kidney; Middle Aged; Organic Anion Transporters; Organic Cation Transport Proteins; Thioglycolates; Treatment Outcome; Triazoles; Uric Acid; Uricosuric Agents; Xanthine Oxidase

The association between human leukocyte antigen (HLA) variants and allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) was evaluated through a pooled analysis of published studies.. A comprehensive search was performed in multiple databases, including PubMed, MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials, and Science Direct. Studies investigating the association between. A total of 4 studies with 81 allopurinol-induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or population controls (general population) were identified. SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls. All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results.. A strong association was found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or TEN, especially in an Asian population.

Topics: Allopurinol; Asian People; Genetic Predisposition to Disease; Gout; Gout Suppressants; HLA Antigens; Humans; Hyperuricemia; Stevens-Johnson Syndrome

Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

Topics: Allopurinol; Genome-Wide Association Study; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Precision Medicine; Prognosis; Uric Acid

Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. Areas covered: In this article, we describe the role of currently available drug therapies for managing acute gout flares and used in reducing serum urate levels. Further, we explore the role of novel small molecular therapies and biologic agents in the treatment of refractory or severe gout symptoms. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-June 2017) was conducted utilizing the key words 'gout', 'interleukin-1 inhibitors', 'acute gout', 'gout treatment', 'urate lowering therapies', 'hyperuricemia', 'colchicine', 'pegloticase', 'lesinurad', 'xanthine oxidase', 'xanthine oxidase inhibitors', 'allopurinol', 'febuxostat', 'uricosurics', 'probenecid', and 'benzbromarone'. All published articles regarding therapeutic management of gout and hyperuricemia were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Expert opinion: Numerous therapies are currently available to managing acute gout flares and for lowering serum urate levels; advances in the understanding of the pathophysiology of this disorder has led to the emergence of targeted therapies and novel biologic preparations currently in development which may improve the clinical management of severe or refractory cases of disease that fail to respond to traditional therapies.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans; Practice Guidelines as Topic; Severity of Illness Index; Treatment Outcome; Uric Acid; Xanthine Oxidase

To determine whether prospective testing for HLA-B*58:01, as a strategy to prevent serious adverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the National Health Service in the UK.. A systematic review and meta-analysis for the association of HLA-B*58:01 with cutaneous and hypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetime costs and outcomes associated with testing vs standard care (with febuxostat prescribed for patients who test positive). Scenario analyses assessed alternative treatment assumptions and patient populations.. The number of patients needed to test to prevent one case of adverse drug reaction was 11 286 (95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103 (95% CR: £98, £106) and 0.0023 (95% CR: -0.0006, 0.0055), respectively, resulting in an incremental cost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effective at a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICER below £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 per QALY gained.. Routine testing for HLA-B*58:01 in order to reduce the incidence of adverse drug reactions in patients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing is expected to become cost-effective with reductions in the cost of genotyping, and with the future availability of cheaper, generic febuxostat.

Topics: Adult; Allopurinol; Cost-Benefit Analysis; Drug-Related Side Effects and Adverse Reactions; Female; Genotyping Techniques; Gout; Gout Suppressants; HLA-B Antigens; Humans; Male; Middle Aged; Pharmacogenomic Testing; Quality-Adjusted Life Years; United Kingdom

Hyperuricemia leading to urate crystal formation in tissues represents the pathophysiological mechanism of gout. Guidelines recommend a therapeutic target of serum urate concentration (sUA) <6 mg/dL, or even lower (≤5 mg/dL) in patients with large deposits. We conducted an analysis with the aim to achieve additional insights into the urate-lowering efficacy of two xanthine oxidase inhibitors, allopurinol and febuxostat.. This was a pooled analysis of phase III trials on allopurinol and febuxostat, including 4101 patients with gout and hyperuricemia. The efficacy outcomes were: mean reduction of sUA concentration from baseline; number of patients with target sUA levels (<6.0 mg/dL or ≤5 mgdL); time to reach target sUA levels.. Three registrative, phase III, randomized, multicenter, placebo-controlled/allopurinol-controlled trials assessing the efficacy of febuxostat, were included. The mean reduction of sUA concentration with any dose of febuxostat was higher (-2.92±2.87 mg/dL; -27%), with respect to placebo- (-0.62±1.84 mg/dL; -5%) and allopurinol-pooled groups (-2.41±2.20 mg/dL; -24%). Moreover, febuxostat showed a higher probability to achieve the recommended target sUA concentration than allopurinol [odds ratio: 2.43 (95% CI: 2.119-2.789) and 4.05 (95% CI: 3.41-4.82) for sUA levels <6 mg/dL and ≤5 mg/dL, respectively]. Patients on any-dose febuxostat reached target sUA faster than allopurinol-treated patients (86.04±71.47 vs. 98.76±70.88 days and 52.08±49.97 vs. 90.42±68.03 days for reaching sUA levels <6 mg/dL and ≤5 mg/dL, respectively; p <0.001 for both comparisons).. In patients with gout and hyperuricemia, febuxostat was significantly more effective and faster than allopurinol in obtaining the recommended target sUA levels, which were reached by a higher number of patients. Therefore, febuxostat was confirmed as an effective option for the treatment of hyperuricemia in gout.

Topics: Adult; Allopurinol; Clinical Trials, Phase III as Topic; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Uric Acid

The research progress of puerarin and its derivatives in anti-inflammatory and anti-gout activities was reviewed in this paper. Puerarin possesses anti-inflammatory activity by affecting immunocyte, inflammation cytokines and signaling pathway. Puerarin also has anti-gout activity through inhibition of xanthine oxidase, promoting the excretion of uric acid to reduce serum uric acid level. Although its ability in reducing uric acid level was lower than that of allopurinol in clinical application, puerarin can also enhance the total antioxidant and free radical scavenging with stronger anti-inflammatory effect, so it will be a promising research direction to find new drugs with better anti-gout activity and less side effects by modifying the chemical structure of puerarin.

Topics: Anti-Inflammatory Agents; Gout; Gout Suppressants; Humans; Isoflavones; Uric Acid; Xanthine Oxidase

Xanthine oxidase (XO) is a versatile molybdoflavoprotein, widely distributed, occurring in milk, kidney, lung, heart, and vascular endothelium. Catalysis by XO to produce uric acid and reactive oxygen species leads to many diseases. Anti hyperuricemic therapy by xanthine oxidase inhibitors has been mainly employed for the treatment of gout. Area covered: This review covers the patent literature (2011-2015) and also presents the interesting strategies/rational approaches employed for the design of xanthine oxidase inhibitors reported recently. Expert opinion: Recent literature indicates that various non purine scaffolds have been extensively investigated for xanthine oxidase inhibition. The significant potential endowed by heteroaryl based compounds, in particularly fused heterocycles clearly highlights their clinical promise and the need for detailed investigation. Studies by various research groups have also revealed that the flavone framework is open for isosteric replacements and structural modifications for yielding potent non purine xanthine oxidase inhibitors. In addition, various plant extracts recently reported to possess significant xanthine oxidase inhibitory potential presents enough promise to initiate a screening program for the identification of other plant extracts and phytoconstituents possessing inhibitory potential towards the enzyme.

Topics: Animals; Drug Design; Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Hyperuricemia; Patents as Topic; Plant Extracts; Xanthine Oxidase

Although gout is one of the most common forms of inflammatory arthritis, it has been relatively neglected until recently. Despite progress in many areas of pathophysiology and genetics of gout and the development of new urate lowering therapies, there remain a number of unanswered clinical questions. With the resurgence of interest in gout it is important to recognize key aspects of gout management that remain challenging and require further research.. The unanswered clinical issues outlined in this review are basic aspects of gout management that clinicians treating people with gout face on a daily basis and include when urate lowering therapy should be commenced, the most appropriate target serum urate, use of prophylaxis when starting urate lowering therapy and the most appropriate urate lowering therapy, particularly for those with chronic kidney disease.. Some of the issues outlined in this article are the subject of ongoing clinical research and some, such as use of allopurinol in people with chronic kidney impairment, may be less relevant with the advent of potentially safer urate lowering therapies but until that time further understanding to aid clinical decision-making is required.

Topics: Allopurinol; Benzbromarone; Colchicine; Disease Progression; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Patient Care Planning; Probenecid; Renal Insufficiency, Chronic; Uric Acid; Uricosuric Agents

Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol. Significant aspects discussed are the importance of adherence to allopurinol therapy, allopurinol hypersensitivity reactions and insights into hyperuricemia. Expert opinion: The initial dosage of allopurinol should be low, particularly in patients with renal impairment. The dose should then be increased slowly until plasma concentrations of urate are sufficient to dissolve monosodium urate crystals (≤ 0.36 mmol/L). For this target, the maintenance dose of allopurinol can be estimated from the equation: Dose = 1413*(U

Topics: Allopurinol; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Medication Adherence; Renal Insufficiency; Treatment Outcome; Uric Acid

Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed.

Topics: Cardiovascular Diseases; Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid; Xanthine Oxidase

Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.

Topics: Allopurinol; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; Genetic Testing; Gout; HLA-B Antigens; Kidney; Oxypurinol; Skin; T-Lymphocytes

Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

Topics: Allopurinol; Creatinine; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney; Renal Dialysis; Renal Insufficiency, Chronic

The prevalence of (asymptomatic) hyperuricemia and gout has substantially increased in recent decades. This development is due to fundamental lifestyle changes, dramatically rising prevalence of obesity and metabolic syndrome, as well as the increasing age of patients. Therefore, medical treatment of hyperuricemia has regained interest in recent years, in particular since after decades of therapeutic stagnation, new treatments of hyperuricemia have been approved or are currently being investigated in clinical trials. European and American guidelines/recommendations for treatment of hyperuricemia and gout have been updated and revised. Furthermore, the role of asymptomatic hyperuricemia as an (independent) cardiovascular risk factor is again under debate. This article provides assistance in integrating our present knowledge in a therapeutic context and summarizes currently recommended treatment strategies.

Topics: Allopurinol; Evidence-Based Medicine; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Internationality; Practice Guidelines as Topic; Treatment Outcome; Uricosuric Agents

This article presents recent epidemiologic contributions focusing on gout-related conditions, especially if controversial, to find plausible, despite hypothetical, mechanistic explanations from the clinician perspective.. The prevalence of gout is increasing, but it is only partially clear that the incidence may be increasing as well. Direct associations of gout with increased risk of diabetes, black races, neurodegenerative disorders, and sugar-enriched foods have been recently questioned. A negative association with smoking has been reported, and new evidence shows that the impact of diet may be independent of obesity. Kidney disease and diuretics have been confirmed to be associated with gout, whereas new data on aging and menopause have come to challenge apparently established disease mechanisms. Regarding treatments, increase in bladder cancer associated with chronic allopurinol use has been reported, and the positive effect of urate-lowering treatment on cardiovascular events has been contested.. Epidemiological data in gout-related conditions are still evolving and claim for future cohort or intervention studies to prove causality. Controversies in epidemiological results fertilize the ground for studies to prove mechanisms and causality and provides a unique opportunity for clinical intervention to improve outcomes, especially with regard to treatments.

Topics: Allopurinol; Cardiovascular Diseases; Comorbidity; Diuretics; Gout; Gout Suppressants; Humans; Incidence; Neurodegenerative Diseases; Obesity; Prevalence

Lesinurad (ZURAMPIC(®)) is an oral urate-anion exchanger transporter 1 (URAT1) inhibitor developed by Ardea Biosciences (a subsidiary of AstraZeneca) for the treatment of hyperuricaemia associated with gout. It reduces serum uric acid (sUA) levels by inhibiting the function of the transporter proteins (URAT1 and organic anion transporter 4) involved in uric acid reabsorption in the kidney. In December 2015, lesinurad was approved in the USA as combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricaemia associated with gout in patients who have not achieved sUA target levels with a xanthine oxidase inhibitor alone. Lesinurad has also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for this indication and is in phase III development as a combination therapy in several other countries. This article summarizes the milestones in the development of lesinurad leading to this first approval for hyperuricaemia associated with gout.

Topics: Clinical Trials as Topic; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Thioglycolates; Triazoles; Uricosuric Agents; Xanthine Oxidase

In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently-used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout.. The following efficacy outcomes were considered in the meta-analysis: (1) % of patients meeting the therapeutic target for sUA level (<6 mg/dl) and (2) percentage reduction in sUA concentration at the end of the study compared with baseline values. An explorative analysis on safety was also conducted.. In total, 16 papers concerned febuxostat, 15 allopurinol, 4 benzbromarone and none involved probenecid. Overall, 70.7% of patients reached the target of sUA with febuxostat therapy; the reduction in sUA was 45.3%. Corresponding figures with allopurinol were 44.4% and 33.8%, respectively. The number of patients on benzbromarone (N=129) was too low to retrieve definitive findings. The advantage for febuxostat over allopurinol was evident also in patients with renal dysfunction. Safety analysis favored febuxostat over allopurinol (OR 0.85; 95% CI: 0.75-0.97).. On the basis of the reported data, febuxostat can play a major role in the treatment of hyperuricaemia and gout. Febuxostat is a suitable pharmacological option for first line treatment of gout, given its established efficacy and safety, documented in a high number of clinical studies and in daily practice.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid

Gouty arthritis is one of the most common rheumatic diseases. The clinical burden of gouty arthritis has historically been well recognized; however, gout is often misdiagnosed and mismanaged. The prevalence of gout is rising and is likely attributed to several factors including increased incidence of comorbidities, lifestyle factors, and increased use of causative medications. With the increasing prevalence, there have been several innovations and evidence-based updates related to the diagnosis and management of gout. Acute gouty arthritis should be treated with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids, or a combination of two agents. Xanthine oxidase inhibitor therapy remains the consensus first-line treatment option for the prevention of recurrent gout. Add-on therapies that reduce serum urate concentration include traditional uricosuric agents and a novel uric acid reabsorption inhibitor. Prophylaxis of acute gout with NSAIDs, colchicine, or corticosteroids is universally recommended when initiating any urate-lowering therapy in order to prevent acute gouty arthritis for a period of at least 6 months. In this review, we discuss the epidemiology and risk factors for gouty arthritis and evaluate diagnostic strategies and therapeutic regimens for the management of gout, including a new drug approval.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Colchicine; Gout; Humans; Hyperuricemia; Uric Acid; Xanthine Oxidase

Flexor tenosynovitis of the hand is often caused by trauma or infection. Gouty tenosynovitis is an uncommon presentation of the condition and is usually misdiagnosed as infection with the patient undergoing surgery. The coexistence of infection and gout causing flexor tenosynovitis has never been described before in the literature; we report the first ever case and emphasise the importance of its awareness for optimal treatment. A 54-year-old man was initially diagnosed and treated as having infective flexor tenosynovitis and, later, due to a lack of improvement in his symptoms, was discovered to also have gout. We review the literature and suggest management strategy for use in daily clinical practice, including an algorithm, for this presentation.

Topics: Allopurinol; Colchicine; Fingers; Gout; Gout Suppressants; Humans; Male; Middle Aged; Recurrence; Staphylococcal Infections; Staphylococcus aureus; Tenosynovitis; Treatment Outcome

Topics: Allopurinol; Arthritis, Gouty; Chronic Disease; Diet Therapy; Female; Gout; Health Care Costs; Humans; Incidence; Male; Needs Assessment; Patient Care Planning; Prognosis; Risk Assessment

Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism and converts hypoxanthine to xanthine, and xanthine into uric acid. When concentrations of uric acid exceed its biochemical saturation point, crystals of uric acid, in the form of monosodium urate, emerge and can predispose an individual to gout, the commonest form of inflammatory arthritis in men aged over 40 years. XOR inhibitors are primarily used in the treatment of gout, reducing the formation of uric acid and thereby, preventing the formation of monosodium urate crystals. Allopurinol is established as first-line therapy for gout; a newer alternative, febuxostat, is used in patients unable to tolerate allopurinol. This review provides an overview of gout, a detailed analysis of the structure and function of XOR, discussion on the pharmacokinetics and pharmacodynamics of XOR inhibitors-allopurinol and febuxostat, and the relevance of XOR in common comorbidities of gout.

Topics: Allopurinol; Animals; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Hypoxanthine; Uric Acid; Xanthine Dehydrogenase

Topics: Clinical Trials as Topic; Gout; Humans; Hyperuricemia; Thioglycolates; Triazoles; Uricosuric Agents; Xanthine Oxidase

Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014).. (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis.. rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.

Topics: Allopurinol; Biomarkers; Down-Regulation; Gout; Gout Suppressants; Humans; Hyperuricemia; Odds Ratio; Risk Factors; Treatment Outcome; Uric Acid

Gout is a common inflammatory arthritis affecting almost 6% of US males and 2% of US females. The central cause of gout is deposition of monosodium urate crystals, and the focus of treatment is aimed at crystal dissolution using urate-lowering therapy.. The review describes the current treatments for urate-lowering therapy including allopurinol, febuxostat, probenecid, benzbromarone and pegloticase. Anti-inflammatory treatment of acute flares and prophylaxis of flares with NSAIDs, colchicine, corticosteroids and anti-IL-1 agents is also reviewed. In addition, drugs in Phase III clinical trials for gout indications are reviewed.. In the last decade, there has been major progress in the pharmacotherapy of gout. Management guidelines have emphasized the importance of a therapeutic serum urate target for effective gout management. Studies have identified the safe and effective dosing strategies for 'old' drugs such as allopurinol and colchicine. New therapeutic agents have been developed and approved for both urate-lowering therapy and anti-inflammatory treatment of acute flares. However, quality of care remains a major challenge in gout management, and strategies to ensure best practice require further focus to ensure that the progress of the last decade translates into clinical benefit for people with gout.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Benzbromarone; Clinical Trials, Phase III as Topic; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Probenecid; Thiazoles; Urate Oxidase; Uric Acid

Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. The xanthine oxidase inhibitor, allopurinol, has historically been the principle agent utilized for reducing elevated uric acid levels and treating underlying cause of gout symptoms; the availability of febuxostat, a newer non-purine selective xanthine oxidase inhibitor, represents an alternative therapy for those patients with contraindications or intolerance to allopurinol.. This article reviews the published literature on the pharmacologic characteristics and clinical safety and efficacy data on the use of febuxostat in the treatment of gout. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-November 2014) was conducted utilizing the key words 'febuxostat', 'allopurinol', and 'gout'. All published articles regarding febuxostat were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed.. Febuxostat has shown benefit with respect to symptomatic relief and uric acid level reduction. The safety profile of this agent makes it an ideal alternative in those patients with contraindications to or who are intolerant of allopurinol.

Topics: Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles; Xanthine Oxidase

The purpose of this study is to give an overview of recently published articles covering the impact of anti-inflammatory therapies, xanthine oxidase inhibitors and other urate-lowering therapies on cardiovascular diseases in gout.. In patients with gout, long-term xanthine oxidase inhibition might reduce some cardiovascular comorbidities because of the dual effect of lowering serum uric acid levels and reducing free-radical production during uric acid formation. Among the anti-inflammatory therapies, colchicine has been shown to reduce some major cardiovascular events.. Epidemiological and experimental studies have shown that hyperuricaemia and gout are independent risk factors for cardiovascular diseases. The mechanisms that link high serum uric acid levels and gout with cardiovascular diseases are multifactorial, implicating low-grade systemic inflammation and xanthine oxidase activity as well as the deleterious effect of hyperuricaemia itself.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Enzyme Inhibitors; Gout; Humans; Uricosuric Agents; Xanthine Oxidase

Inadequate patient information about gout may contribute to poor disease outcomes. We reviewed existing educational resources for gout to identify strengths and weaknesses and compare resources cross-nationally.. Content, readability, and dietary recommendations were reviewed using a sample of 30 resources (print and Web-based) from 6 countries.. More than half of the resources were written at a highly complex level. Some content areas were lacking coverage, including comorbidity risks, uric acid target levels, and continuing allopurinol during acute attacks.. Our findings suggest significant room for improvement in gout patient educational resources, particularly regarding self-management.

Topics: Allopurinol; Analysis of Variance; Chi-Square Distribution; Female; Gout; Health Knowledge, Attitudes, Practice; Humans; Internet; Male; Medical Informatics; Needs Assessment; New Zealand; Patient Education as Topic; Severity of Illness Index

Gout is one of the most common forms of arthritis and the prevalence is increasing. Management comprises rapid and effective control of the inflammation in acute gout and sustained urate lowering in the long term. Improving the outcomes for cheaper old drugs and for the increasing number of new, more expensive agents is an important clinical goal. The role of pharmacogenetics in predicting response and adverse events to gout therapies is of considerable interest. Currently, prospective screening is employed to detect HLA-B*5801 carriage and glucose-6-phosphate dehydrogenase deficiency, to minimize occurrence of allopurinol hypersensitivity and pegloticase-related hemolytic anemia. In the future it is likely that other genetic markers of drug response will make the transition to clinical practice to further improve the efficacy and safety of gout therapies. In this review, we will examine the potential clinical relevance of specific genetic variants in the management of gout.

Topics: Allopurinol; Gout; HLA-B Antigens; Humans; Pharmacogenetics; Treatment Outcome; Uric Acid

Topics: Allopurinol; Gout; Humans; Male; Medication Adherence; Middle Aged; Quality Indicators, Health Care; Reference Values; Uric Acid

Recent interest in gout has led to development of new drugs for acute gout and long-term urate-lowering, as well as interest in improving the use of older drugs. The patients' comorbidities and concomitant medications may contribute to the risk of adverse drug reactions with anti-gout therapies. This review will highlight recent data on the safety of drugs used in gout.. Colchicine has a narrow therapeutic index, and low doses are effective with less gastrointestinal toxicity. There are significant interactions between colchicine and CYP3A4 and P-glycoprotein inhibitors, and the colchicine dose must be reduced. Allopurinol and febuxostat have similar adverse effect profiles. Recent data have highlighted the risk association of HLA-B5801 in some ethnic groups and of allopurinol starting dose in allopurinol hypersensitivity syndrome. Further long-term cardiovascular safety data in patients with cardiovascular disease or cardiovascular risk factors receiving febuxostat and allopurinol are pending. Infusion reactions are common in patients receiving pegloticase, particularly in patients with pre-infusion serum urate above 0.36mmol/l (6 mg/dl).. In general, treatments for gout are well tolerated, although clinicians must keep in mind the potential for drug interactions and the contribution of comorbidities to the potential for adverse effects with gout therapies.

Topics: Allopurinol; Colchicine; Drug Interactions; Febuxostat; Gout; Gout Suppressants; HLA-B Antigens; Humans; Interleukin-1; Polyethylene Glycols; Risk Factors; Safety; Thiazoles; Urate Oxidase

Although uricosuric agents provide the most time-honoured approach to the control of hyperuricemia, their place in the armamentarium has been eclipsed by that of xanthine oxidase inhibitors. This review considers the potential for uricosuric agents from the perspective of recent progress in the understanding of urate transport systems.. No new agents have yet become available, but promising new drugs are under development. Better understanding of the transporters URAT1 and ABCG2 in particular would appear to provide opportunities for more selective, better tolerated agents to increase the renal clearance of uric acid and thereby control hyperuricemia.. Conceptually, modest inhibition of renal tubular reabsorption should provide effective relief for the millions of individuals who are now hyperuricemic and who suffer from its principal consequence, gout.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Drug Discovery; Enzyme Inhibitors; Glucose Transport Proteins, Facilitative; Gout; Humans; Hydrochlorothiazide; Hyperuricemia; Kidney Tubules, Proximal; Neoplasm Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Probenecid; Uric Acid; Uricosuric Agents; Xanthine Oxidase

The incidence of gout and hyperuricemia has been increasing. The demand for new anti-gout therapies today presents exciting opportunities to organizations and individuals offering such products.. This review analyzes the patents of anti-gout products to help pharmaceutical companies and individuals in the patenting of potential candidate drugs for gout treatment in China.. In this review, 786 patents were found, among which, 215 are in the protection period. The latter group of patents includes 183 patents for traditional Chinese medicines (TCM, 85%), 30 for synthetic compounds (14%) and 2 for combinations of synthetic compounds and TCM (CST). Among the TCM patents, 84% contain various dosage formulae for different Chinese medicines, 13% are herbal extracts and only 7 patents are from herbal extract derivatives. Synthetic compound patents mainly target xanthine oxidase, urate transporter 1 and uric acid oxidase. Searching for new targets and drugs acting on multiple targets should provide a new stimulus in the field of synthetic compound patents. CST has the smallest proportion of Chinese anti-gout patents, although it is still in the test stage and has not been widely accepted, but has provided a new direction for the field of anti-gout patents.

Topics: China; Drugs, Chinese Herbal; Enzyme Inhibitors; Gout; Humans; Medicine, Chinese Traditional; Patents as Topic; Xanthine Oxidase

Topics: Adult; Allopurinol; Biopsy, Needle; Diagnosis, Differential; Follow-Up Studies; Gout; Humans; Immunohistochemistry; Male; Panniculitis; Rare Diseases; Risk Assessment; Severity of Illness Index; Skin; Skin Diseases; Treatment Outcome; Uric Acid

Gout is currently one of the most common causes of inflammatory arthritis in most industrialised countries. Apart from its high frequency, gout is associated with disability, poor quality of life and increased mortality and therefore represents an ever increasing public health concern. Substantial experimental and epidemiological evidence exists supporting the link between elevated levels of serum uric acid and several comorbidities including cardiovascular and kidney diseases. The cornerstone of effective gout management is long-term serum urate lowering below saturation concentrations (<6 mg/dL or <360 μmol/L) in order to promote crystal dissolution and prevent monosodium urate crystals formation. The management of gout includes not only pharmacological approaches, but also a number of nonpharmacologic interventions aiming at lessening attack risk, lowering uric acid levels and promoting general health while preventing the development of comorbidities. It is of great address whether urate lowering strategies can also lower cardiovascular risk and some preliminary studies in both animal and human subjects suggest that they might. Patient education and appropriate lifestyle advice are core aspects of management of hyperuricemia and gout. The two xanthine oxidase inhibitors currently available are effective as long-term urate lowering therapy although the greater efficacy and good tolerability of febuxostat as urate lowering agent has to be adequately considered especially when the reduction of serum uric acid levels to achieve the target is particularly ambitious and/or the presence of comorbidities increases the risk of adverse effects. Associated comorbidities and cardiovascular risk factors should be also addressed as an important part of the management of chronic hyperuricemia and gout.

Topics: Allopurinol; Cardiovascular Diseases; Chronic Disease; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Life Style; Patient Education as Topic; Thiazoles; Xanthine Oxidase

Gout is a common disorder with clinical signs and symptoms resulting from inflammatory responses to monosodium urate crystals deposited in tissues from extracellular fluids saturated for urate. Long-term management of gout focuses on nonpharmacologic and pharmacologic means to achieve and maintain serum urate levels in a subsaturating range. Despite a firm understanding of gout pathophysiology, means to achieve certain diagnosis, and a variety of effective therapies, treatment outcomes remain suboptimal. In this review, available nonpharmacologic and pharmacologic therapies for chronic gout are discussed and a framework is provided for successful achievement and maintenance of goal-range serum urate levels.

Topics: Allopurinol; Benzbromarone; Chronic Disease; Febuxostat; Feeding Behavior; Gout; Gout Suppressants; Humans; Hyperuricemia; Polyethylene Glycols; Risk Reduction Behavior; Thiazoles; Urate Oxidase; Uricosuric Agents

The purpose of this review article is to outline plants currently used and those with high promise for the development of anti-gout products. All relevant literature databases were searched up to 25 March 2013. The search terms were 'gout', 'gouty arthritis', 'hyperuricemia', 'uric acid', 'xanthine oxidase (XO) inhibitor', 'uricosuric', 'urate transporter 1(URAT1)' and 'glucose transporter 9 (GLUT9)'. Herbal keywords included 'herbal medicine', 'medicinal plant', 'natural products', 'phytomedicine' and 'phytotherapy'. 'antiinflammatory effect' combined with the words 'interleukin-6 (IL-6)', 'interleukin-8 (IL-8)', 'interleukin-1beta (IL-1beta)', and 'tumor necrosis factor alpha (TNF-alpha)'. XO inhibitory effect, uricosuric action, and anti-inflammatory effects were the key outcomes. Numerous agents derived from plants have anti-gout potential. In in vitro studies, flavonoids, alkaloids, essential oils, phenolic compounds, tannins, iridoid glucosides, and coumarins show the potential of anti-gout effects by their XO inhibitory action, while lignans, triterpenoids and xanthophyll are acting through their anti-inflammatory effects. In animal studies, essential oils, lignans, and tannins show dual effects including reduction of uric acid generation and uricosuric action. Alkaloids reveal inhibit uric acid generation, show anti-inflammatory effects, or a combination of the two. Phenolic compounds and flavonoids inhibit uric acid production, show uricosuric anti-inflammatory effects. In the rare human studies, colchicine from Colchicum autumnale showed anti-inflammatory effects while for other plant extracts, although revealing anti-gout potential, further phytochemical investigations are needed to identify their active constituents. Besides, the plants which give antioxidant activities are much potent in the management of gout and need to be further investigated. The current review is a detailed discussion of the potential of medicinal plants for treatment of gout.

Topics: Animals; Anti-Inflammatory Agents; Gout; Humans; Hyperuricemia; Phytotherapy; Plants, Medicinal; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Colchicine; Evidence-Based Medicine; Febuxostat; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Quality of Life; Thiazoles; Urate Oxidase

Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol.. The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.. The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions.. It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target.

Topics: Allopurinol; Biomarkers; Dose-Response Relationship, Drug; Gout; Gout Suppressants; Humans; Patient Compliance; Treatment Failure; Uric Acid

The prevalence of gout in the US population is steadily increasing. Genome-wide research has found several variants of DNA sequences that predispose patients to irregular uric acid metabolism. Comorbidities linked to gout include obesity and cardiovascular disease. Though the formal diagnosis is made with arthrocentesis and subsequent analysis, CT and ultrasound findings supplement the diagnosis and monitor disease management. Newer immunologic agents are available for patients whose disease is refractory to standard therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Urate Oxidase; Uricosuric Agents; Xanthine Oxidase

Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

Topics: Allopurinol; Cardiovascular Diseases; Colchicine; Diabetes Mellitus, Type 2; Disease Management; Gout; Gout Suppressants; Humans; Hyperuricemia; Inflammation; Metabolic Syndrome; Probenecid; Renal Insufficiency, Chronic; Treatment Outcome; Uricosuric Agents; Xanthine Oxidase

Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent.. To assess the efficacy and safety of dietary supplementation for people with chronic gout.. We performed a search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL on 6 June 2013. We applied no date or language restrictions. In addition, we performed a handsearch of the abstracts from the 2010 to 2013 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conferences, checked the references of all included studies and trial registries.. We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents and vitamins. The main outcomes were reduction in frequency of gouty attacks and trial participant withdrawal due to adverse events. We also considered pain reduction, health-related quality of life, serum uric acid (sUA) normalisation, function (i.e. activity limitation), tophus regression and the rate of serious adverse events.. We used standard methodological procedures expected by The Cochrane Collaboration.. We identified two RCTs (160 participants) that fulfilled our inclusion criteria. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP and sUA reduction for vitamin C), we reported the results separately.One trial including 120 participants, at moderate risk of bias, compared SMP enriched with glycomacropeptides (GMP) with unenriched SMP and with lactose over three months. Participants were predominantly men aged in their 50's who had severe gout. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the study period.The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were uncertain (mean ± standard deviation (SD) flares per month: 0.49 ± 1.52 in SMP/GMP/G60 group versus 0.70 ± 1.28 in control groups; mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar in both groups although again the results were imprecise (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; risk ratio (RR) 1.27, 95% CI 0.53 to 3.03; low-quality evidence). The findings for adverse events were also uncertain (2/40 in SMP/GMP/G600 group versus 3/80 in control groups; RR 1.33, 95% CI 0.23 to 7.66; low-quality evidence). Gastrointestinal events were the most commonly reported adverse effects. Pain from self reported gout flares (measured on a 10-point Likert scale) improved slightly more in the SMP/GMP/G600 group compared with controls (mean ± SD reduction -1.97 ± 2.28 points in SMP/GMP/G600 group versus -0.94 ± 2.25 in control groups; MD -1.03, 95% CI -1.96 to -0.10; low-quality evidence). This was an absolute reduction of 10% (95% CI 20% to 1% reduction), which may not be of clinical relevance. Results were imprecise for the outcome improvement in physical function (mean ± SD Health Assessment Questionnaire (HAQ)-II (scale 0 to 3, 0 = no disability): 0.08 ± 0.23 in SMP/GMP/G60 group versus 0.11 ± 0.31 in control groups; MD -0.03, 95% CI -0.14 to 0.08; low-quality evidence). Similarly, results for sUA reduction were imprecise (mean ± SD reduction: -0.025 ± 0.067 mmol/L in SMP/GMP/G60 group versus -0.010 ± 0.069 in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). Th. While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.

Topics: Adult; Allopurinol; Animals; Ascorbic Acid; Chronic Disease; Dietary Supplements; Gout; Humans; Lactose; Milk; Peptides; Powders; Randomized Controlled Trials as Topic

Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout.. To assess the efficacy and safety of allopurinol compared with placebo and other urate-lowering therapies for treating chronic gout.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE on 14 January 2014. We also handsearched the 2011 to 2012 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts, trial registers and regulatory agency drug safety databases.. All randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs) that compared allopurinol with a placebo or an active therapy in adults with chronic gout.. We extracted and analysed data using standard methods for Cochrane reviews. The major outcomes of interest were frequency of acute gout attacks, serum urate normalisation, pain, function, tophus regression, study participant withdrawal due to adverse events (AE) and serious adverse events (SAE). We assessed the quality of the body of evidence for these outcomes using the GRADE approach.. We included 11 trials (4531 participants) that compared allopurinol (various doses) with placebo (two trials); febuxostat (four trials); benzbromarone (two trials); colchicine (one trial); probenecid (one trial); continuous versus intermittent allopurinol (one trial) and different doses of allopurinol (one trial). Only one trial was at low risk of bias in all domains. We deemed allopurinol versus placebo the main comparison, and allopurinol versus febuxostat and versus benzbromarone as the most clinically relevant active comparisons and restricted reporting to these comparisons here.Moderate-quality evidence from one trial (57 participants) indicated allopurinol 300 mg daily probably does not reduce the rate of gout attacks (2/26 with allopurinol versus 3/25 with placebo; risk ratio (RR) 0.64, 95% confidence interval (CI) 0.12 to 3.52) but increases the proportion of participants achieving a target serum urate over 30 days (25/26 with allopurinol versus 0/25 with placebo, RR 49.11, 95% CI 3.15 to 765.58; number needed to treat for an additional beneficial outcome (NNTB) 1). In two studies (453 participants), there was no significant increase in withdrawals due to AE (6% with allopurinol versus 4% with placebo, RR 1.36, 95% CI 0.61 to 3.08) or SAE (2% with allopurinol versus 1% with placebo, RR 1.93, 95% CI 0.48 to 7.80). One trial reported no difference in pain reduction or tophus regression, but did not report outcome data or measures of variance sufficiently and we could not calculate the differences between groups. Neither trial reported function.Low-quality evidence from three trials (1136 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 300 mg daily versus febuxostat 80 mg daily over eight to 24 weeks (21% with allopurinol versus 23% with febuxostat, RR 0.89, 95% CI 0.71 to 1.1); however more participants may achieve target serum urate level (four trials; 2618 participants) with febuxostat 80 mg daily versus allopurinol 300 mg daily (38% with allopurinol versus 70% with febuxostat, RR 0.56, 95% CI 0.48 to 0.65, NNTB with febuxostat 4). Two trials reported no difference in tophus regression between allopurinol and febuxostat over a 28- to 52-week period; but as the trialists did not provide variance, we could not calculate the mean difference between groups. The trials did not report pain reduction or function. Moderate-quality evidence from pooled data from three trials (2555 participant. Our review found low- to moderate-quality evidence indicating similar effects on withdrawals due to AEs and SAEs and incidence of acute gout attacks when allopurinol (100 to 600 mg daily) was compared with placebo, benzbromarone (100 to 200 mg daily) or febuxostat (80 mg daily). There was moderate-quality evidence of little or no difference in the proportion of participants achieving target serum urate when allopurinol was compared with benzbromarone. However, allopurinol seemed more successful than placebo and may be less successful than febuxostat (80 mg daily) in achieving a target serum urate level (6 mg/dL or less; 0.36 mmol/L or less) based on moderate- to low-quality evidence. Single studies reported no difference in pain reduction when allopurinol (300 mg daily) was compared with placebo over 10 days, and no difference in tophus regression when allopurinol (200 to 300 mg daily) was compared with febuxostat (80 mg daily). None of the trials reported on function, health-related quality of life or participant global assessment of treatment success, where further research would be useful.

Topics: Allopurinol; Benzbromarone; Chronic Disease; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Probenecid; Randomized Controlled Trials as Topic; Thiazoles; Uric Acid

Uricosuric agents have long been used in the treatment of gout but there is little evidence regarding their benefit and safety in this condition.. To assess the benefits and harms of uricosuric medications in the treatment of chronic gout.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4, 2013), Ovid MEDLINE and Ovid EMBASE for studies to the 13 May 2013. We also searched the World Health Organization Clinical Trials Registry, ClinicalTrials.gov and the 2011 to 2012 American College of Rheumatology and European League against Rheumatism abstracts. WE considered black box warnings and searched drug safety databases to identify and describe rare adverse events.. We considered all randomised controlled trials (RCTs) or quasi-randomised controlled trials (controlled clinical trials (CCTs)) that compared uricosuric medications (benzbromarone, probenecid or sulphinpyrazone) alone or in combination with another therapy (placebo or other active uric acid-lowering medication, or non-pharmacological treatment) in adults with chronic gout for inclusion.. Two review authors independently selected the studies for inclusion, extracted data and performed a risk of bias assessment. Main outcomes were frequency of acute gout attacks, serum urate normalisation, study participant withdrawal due to adverse events, total adverse events, pain reduction, function and tophus regression.. The search identified four RCTs and one CCT that evaluated the benefit and safety of uricosurics for gout. One study (65 participants) compared benzbromarone with allopurinol for a duration of four months; one compared benzbromarone with allopurinol (36 participants) for a duration of nine to 24 months; one study (62 participants) compared benzbromarone with probenecid for two months and one study (74 participants) compared benzbromarone with probenecid. One study (37 participants) compared allopurinol with probenecid. No study was completely free from bias.Low-quality evidence from one study (55 participants) comparing benzbromarone with allopurinol indicated uncertain effects in terms of frequency of acute gout attacks (4% with benzbromarone versus 0% with allopurinol; risk ratio (RR) 3.58, 95% confidence interval (CI) 0.15 to 84.13), while moderate-quality evidence from two studies (101 participants; treated for four to nine months) indicated similar proportions of participants achieving serum urate normalisation (73.9% with benzbromarone versus 60% with allopurinol; pooled RR 1.27, 95% CI 0.90 to 1.79). Low-quality evidence indicated uncertain differences in withdrawals due to adverse events (7.1% with benzbromarone versus 6.1% with allopurinol; pooled RR 1.25, 95% CI 0.28 to 5.62), and total adverse events (20% with benzbromarone versus 6.7% with allopurinol; RR 3.00, 95% CI 0.64 to 14.16). The study did not measure pain reduction, function and tophus regression.When comparing benzbromarone with probenecid, there was moderate-quality evidence based on one study (62 participants) that participants taking benzbromarone were more likely to achieve serum urate normalisation after two months (81.5% with benzbromarone versus 57.1% with probenecid; RR 1.43, 95% CI 1.02 to 2.00). This indicated that when compared with probenecid, five participants needed to be treated with benzbromarone in order to have one additional person achieve serum urate normalisation (number needed to treat for an additional beneficial outcome (NNTB) 5). However, the second study reported no difference in the absolute decrease in serum urate between these groups after 12 weeks. Low-quality evidence from two studies (129 participants) indicated uncertain differences between treatments in the frequency of acute gout attacks (6.3% with benzbromarone versus 10.6% with probenecid; pooled RR 0.73, 95% CI 0.09 to 5.83); fewer withdrawals due to adverse events with benzbromarone (2% with ben. There was moderate-quality evidence that there is probably no important difference between benzbromarone and allopurinol at achieving serum urate normalisation, but that benzbromarone is probably more successful than probenecid at achieving serum urate normalisation in people with gout. There is some uncertainty around the effect estimates, based on low-quality evidence from only one or two trials, on the number of acute gout attacks, the number of withdrawals due to adverse events or the total number of participants experiencing adverse events when comparing benzbromarone with allopurinol. However, when compared with probenecid, benzbromarone resulted in fewer withdrawals due to adverse events and fewer participants experiencing adverse events. Low-quality evidence from one small study indicated uncertain effects in the incidence of acute gout attacks when comparing probenecid with allopurinol therapy. We downgraded the evidence because of a possible risk of performance and other biases and imprecision.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Chronic Disease; Controlled Clinical Trials as Topic; Female; Gout; Humans; Male; Middle Aged; Probenecid; Randomized Controlled Trials as Topic; Uric Acid; Uricosuric Agents

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Age Distribution; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Disease Progression; Early Diagnosis; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Needs Assessment; Practice Guidelines as Topic; Prognosis; Risk Assessment; Severity of Illness Index; Sex Distribution; Treatment Outcome; United States; Uric Acid

This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles; Uric Acid

This article discusses the results of clinical and experimental studies that examine the association of hyperuricemia and gout with cardiovascular (CV) disease.. Key papers for inclusion were identified by a PubMed search, and articles were selected for their relevance to the topic, according to the authors' judgment.. Significant progress has been made in confirming an association, possibly causal, between hyperuricemia and CV outcomes. Xantine-oxidase (XO) inhibitors appear to be the most promising agents for prevention and treatment of CV consequences associated with hyperuricemia. Several small and medium sized studies have examined the effect of these agents on CV function in a variety of patient populations. Improvements in measures of endothelial function, oxidative stress, cardiac function, hemodynamics, and certain inflammatory indices have been demonstrated. Compounds for XO inhibition with more specific clinical effects and fewer side effects than allopurinol may be promising options to further explore the therapeutic potential in patients with CV disease. It is too early to make clinical recommendations with regard to the benefits of using XO inhibitor allopurinol or the novel febuxostat in patients with asymptomatic increased UA levels and high CV risk because only a small number of studies have shown that they may be beneficial in terms of CV outcomes. More studies are therefore needed to determine the potential of these drugs for reducing the risk of developing CV disease.

Topics: Cardiovascular Diseases; Gout; Humans; Hyperuricemia; Xanthine Oxidase

Allopurinol is the primary therapy for the management of chronic gout. Utilization of allopurinol has increased in tandem with the growing prevalence of gout globally. This exposes more patients to the risk of allopurinol hypersensitivity (AH), a rare adverse reaction characterised by a spectrum of cutaneous reactions and systemic manifestations. Severe forms of AH have been associated with high mortality. The pathophysiology underlying this reaction remains unknown, but several risk factors have been proposed.. The aim of this study was to review all published cases of AH documented in the literature in order to better understand the constellation of factors predisposing to this reaction, building on previous reviews by Lupton and Odom, Singer and Wallace and Arellano and Sacristan.. A literature search was conducted in MEDLINE and EMBASE to identify relevant articles published between January 1950 and December 2012, with no language restrictions imposed. Articles that were included reported either allopurinol-induced cutaneous manifestations alone or satisfied the diagnostic criteria for AH as defined by Singer and Wallace.. Nine hundred and one patients (overall AH cohort) were identified from 320 publications. Of these patients, 802 satisfied the Singer and Wallace criteria ('Singer and Wallace' cohort) while 99 patients had only mild cutaneous manifestations ('non-Singer and Wallace' cohort). Data were often incomplete; hence the results reported reflect the fractions of the subsets of the cohort where the data in question were available. In the overall AH cohort, 58 % (416/722) were male. The majority (73 %; 430/590) of patients were Asian. Renal impairment (48 %; 182/376) and hypertension (42 %; 160/376) were the most common chronic conditions; accordingly, diuretics (45 %; 114/252) and antihypertensives (39 %; 99/252) were the most prevalent concomitant medications. Allopurinol was prescribed for approved indications (chronic gout and chemoprophylaxis) in only 40 % (186/464) of patients. The median allopurinol dose was 300 mg/day (range 10-1,000 mg/day) and was taken by 50 % (168/338). There was no significant association between a higher dose (>300 mg/day) and an increased risk of severe cutaneous manifestations [odds ratio (OR) 1.76; 95 % CI 0.73-4.22; p = 0.23]. Approximately 90 % (489/538) of patients developed AH within 60 days of initiating allopurinol therapy. Serum oxypurinol (the active metabolite of allopurinol) concentration was only recorded in six patients, four of whom had levels within the putative therapeutic range of 30-100 μmol/L. The HLA-B*5801 allele was present in 99 % (166/167) of patients tested, with the majority (147/166) being of Asian ancestry. The all-cause mortality rate was 14 % (109/788) with 94 AH-related deaths, all of which occurred in the cohort meeting the Singer and Wallace criteria.. The publications included in this review utilized different laboratory reference ranges to classify the non-cutaneous manifestations of AH; this may have introduced some variation in the cases identified as AH. A majority of the articles included in this analysis consisted of case reports and series--publication types that are not recognized as best-quality evidence; this thus limited the conclusions we could draw about the many risk factors we were interested in evaluating.. Risk factors associated with AH, such as concomitant diuretic use, pre-existing renal impairment and recent initiation of allopurinol, were commonly present in AH patients; however, their role in the mechanism of AH remains to be established. A clear risk factor was the HLA-B*5801 status; this was especially relevant in Asian populations where there is a higher carriage rate of the allele. High allopurinol dose, previously suggested to be a risk factor, was not confirmed as such. The paucity of well-documented case reports and studies of AH render it difficult to draw more concrete conclusions or construct a meticulous profile of patients at risk of AH. Future case reports of AH need to be better documented to contribute to understanding the risks for, and mechanisms of, AH.

Topics: Allopurinol; Drug Hypersensitivity; Drug Utilization; Gout; Gout Suppressants; Humans

Gout is a common condition which is mainly treated with the hypo-uricemic agent, allopurinol. Although allopurinol is generally a well-tolerated drug, there is a small risk of developing potentially fatal complications, such as allopurinol hypersensitivity syndrome. Recent advances in pharmacogenomics have made possible the identification of genes which confer susceptibility to specific drugs. A recent multi-national case-control study has reported allopurinol as the most common drug associated with Stevens-Johnson syndrome and toxic epidermal necrolysis. Several studies have established a strong association between the human leukocyte antigen (HLA)-B*5801 gene and development of Stevens-Johnson syndrome and toxic epidermal necrolysis. The allele frequency of HLA-B*5801 is highest in the South East Asian population.Since other hypo-uricemic agents are available, patients may wish to have HLA-B*5801 testing before being started on allopurinol. As the test for HLA-B*5801 is expensive, time-consuming and only available in selected laboratories, there is a need to evaluate the utility and cost-effectiveness of this test in our region.

Topics: Allopurinol; Asia; Australasia; Cost-Benefit Analysis; Drug Hypersensitivity Syndrome; Genetic Predisposition to Disease; Genetic Testing; Gout; Gout Suppressants; Health Care Costs; HLA-B Antigens; Humans; Patient Selection; Pharmacogenetics; Phenotype; Predictive Value of Tests; Risk Factors; Stevens-Johnson Syndrome

To review the evidence surrounding the use of allopurinol in chronic kidney disease (CKD) and discuss safety and efficacy considerations of such use.. A literature search was conducted through MEDLINE (1950-July 2013), PubMed (1965-July 2013), and International Pharmaceutical Abstracts (1970-July 2013) using the search terms allopurinol and kidney or renal. In addition, reference citations from publications identified were reviewed.. All articles in English identified from the data sources were evaluated for inclusion.. Gout management with allopurinol in patients with CKD can be challenging because of the risk of adverse events and uncertain efficacy. Not all gout treatment guidelines provide recommendations for allopurinol use specifically in patients with CKD. Literature regarding the safety and efficacy of dosing allopurinol in CKD has shown inconsistent results and is based primarily on retrospective, case cohort or observational data. Some trials have demonstrated an increased risk of allopurinol-induced adverse reactions in patients with CKD, whereas others have not confirmed renal insufficiency as a risk factor. More CKD patients achieved a target uric acid level in studies where the allopurinol dose was titrated to effect as compared with those studies in which patients were given renally adjusted or untitrated allopurinol doses.. Studies evaluating allopurinol use in patients with CKD have reported inconsistent findings relative to safety and efficacy. Providers should be aware of the potential risk of allopurinol hypersensitivity syndrome as well as the need for reducing the initiation dose and gradual titration of allopurinol to safely achieve a target serum urate level in this population.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Treatment Outcome

To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout.. We did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI).. From 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03-1.30, I(2) = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90-0.99, I(2) = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of <6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22-2.00, I(2) = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares.. Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6 mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Thiazoles; Treatment Outcome; Uric Acid

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Colchicine; Comorbidity; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Education as Topic; Risk Reduction Behavior; Toe Joint; Uric Acid

The increasing prevalence of gout has been accompanied by a growing number of patients intolerant to or with disease refractory to available urate-lowering therapies. These difficult-to-treat patients currently represent about 3 - 5% of people with gout in Europe and the United States, which highlights the need for emerging treatments to effectively lower urate levels.. In this review, the authors describe the putative pharmacological targets to lower urate levels. Furthermore, the authors discuss various strategies used to discover novel molecules or to improve available drugs used to treat gout.. Major advances in our understanding of urate renal transport from in vitro, animal and genetic studies could lead to the development of novel uricosuric drugs. Targeting one or several urate transporters such as urate transporter 1, organic anion transporter 4 and 10 and glucose transporter 9 is promising. Moreover, design of small molecules capable of blocking the site activity of enzymes other than xanthine oxidase and involved in the purine pathway could generate novel hypouricemic drugs. Finally, polyethylene glycol (PEGylation) can significantly extend the biological half-life of drugs and reduce antigenicity and immunogenicity of proteins. The technology has been successfully applied to an uricase (pegloticase), but the drug was immunogenic in some patients. Strategies to decrease the immunogenicity of a PEG-uricase are important for developing next-generation uricase.

Topics: Drug Discovery; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Febuxostat has been approved for the treatment of hyperuricemia in patients with/without gout.. This meta-analysis and systematic review assessed the efficacy and tolerability of febuxostat in hyperuricemic patients with/without gout.. Major electronic databases were searched for articles of all publication years (up to February 2012), as were the Web sites of the American College of Rheumatology, the European League Against Rheumatism, and the Chinese State Food and Drug Administration, and clinicaltrials.gov for unpublished studies. Only randomized, controlled trials (RCTs) were included.. Ten trials were included. A significantly greater proportion of patients achieved the target serum urate level (sUA ≤6.0 mg/dL) at the final visit in the febuxostat group compared with the placebo (OR = 235.73; P < 0.01) and allopurinol groups (OR = 3.14; P < 0.01). In subgroup analysis, the proportion of patients who achieved target sUA at the final visit was significantly greater in the febuxostat-treated group (40 mg/d) compared with the allopurinol-treated group (100-300 mg/d) (50.9% vs 45.6%; OR = 1.25; 95% CI, 1.05-1.49; P = 0.01). As the dosage was increased (40, 80, 120 mg/d), the proportion of patients who achieved target sUA in the febuxostat-treated group increased gradually (50.9%, 71.4%, 82%, respectively). There was no significant difference in the occurrence of adverse events (AEs) between the febuxostat- and allopurinol-treated groups.. Febuxostat was effective in reducing serum urate in hyperuricemic patients with/without gout, and febuxostat (40-120 mg/d) was more efficacious compared with allopurinol (100-300 mg/d). The doses of allopurinol to which febuxostat has been compared, although commonly prescribed, are low in the range of approved doses of allopurinol. The tolerability of febuxostat for the treatment of hyperuricemia with/without gout is similar to that of allopurinol.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Randomized Controlled Trials as Topic; Thiazoles; Uric Acid

Incidence and prevalence of gout have markedly increased over the last few decades in keeping with the rise in prevalence of obesity and metabolic syndrome. Until recently, management of gout in patients with associated metabolic syndrome and comorbid illnesses such as renal impairment was difficult because of limited treatment options. However, significant progress has been made in the last few years, with introduction of new treatments such as interleukin-1 antagonists for management of acute gout, and febuxostat and pegloticase for chronic gout. The association of gout with alcohol, dietary purines and fructose ingestion has been confirmed in large prospective studies, thus enabling the clinician to now provide evidence-based advice to patients. Recent efficacy and safety data favour lower over higher doses of colchicine, and oral corticosteroids over non-steroidal anti-inflammatory drugs for patients with acute gout. Local ice therapy might help to differentiate gout from other forms of inflammatory arthritis, and supplementation with vitamin C help to reduce risk of gout. Several other drugs with rational mechanisms of action are in the pipeline, and likely to be introduced over the next few years. A new era has thus begun in the field of gout.

Topics: Adrenal Cortex Hormones; Alcohol Drinking; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Ascorbic Acid; Colchicine; Comorbidity; Cryotherapy; Diet; Dose-Response Relationship, Drug; Febuxostat; Fructose; Gout; Gout Suppressants; Humans; Interleukin 1 Receptor Antagonist Protein; Polyethylene Glycols; Purines; Receptors, Interleukin-1; Recombinant Fusion Proteins; Thiazoles; Urate Oxidase; Uric Acid; Uricosuric Agents; Vitamins; Xanthine Oxidase

The aim of urate-lowering therapy is to maintain urate concentration below the saturation point for monosodium urate. This therapy dissolves crystal deposits and cures gout while it is maintained. EULAR guidelines recommend that plasma urate should be maintained at a concentration less than 360μM, and the British Guidelines less than 300μM. Urate-lowering therapy is indicated for patients with recurrent gout attacks, chronic arthropathy, tophi, and gout with uric acid stones. Allopurinol lowers uricemia through inhibition of xanthine oxidase activity. The maximum allowed dose is reduced in case of renal failure, which is relatively frequent in gouty patients. Febuxostat has been approved for the treatment of chronic hyperuricemia in conditions where urate deposition has already occurred. Febuxostat is a novel non-purine, selective inhibitor of xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment appears to be necessary in patients with mild-to-moderate renal impairment. Another powerful hypo-uricemic drug is the PEG-uricase (pegloticase). Pegloticase is a uric acid-specific PEGylated recombinant mammalian uricase recently approved by the FDA for treatment of patients with refractory chronic gout.

Topics: Allopurinol; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Guidelines as Topic; Humans; Organ Transplantation; Polyethylene Glycols; Thiazoles; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects.

Topics: Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Glucose Transport Proteins, Facilitative; Gout; Gout Suppressants; Humans; Hyperuricemia; Neoplasm Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Uric Acid

Gout is a metabolic disorder of purine metabolism and uric acid elimination. Over time, acute gout can develop into a chronic, disabling arthropathy, often associated with multiple comorbidities. Gout patients have often been undertreated, partly because of the clinician's perceived risks of a therapy outweighing its potential benefits. The approval of new therapies to treat hyperuricemia in gout has led to a new understanding of gout management and medication safety regarding new and old therapies. This review focuses on potential safety issues of currently available urate-lowering therapies and outlines strategies to minimize risks so their benefits can be reached.

Topics: Allopurinol; Comorbidity; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Risk Factors; Thiazoles; Uric Acid

Gout is the most common inflammatory arthritis in men over 40 years and has an increasing prevalence among postmenopausal women. Lowering serum uric acid levels remains one of the primary goals in the treatment of chronic gout. In clinical trials, febuxostat has been shown to be effective in lowering serum uric acid levels to < 6.0 mg/dL.. To evaluate the benefits and harms of febuxostat for chronic gout.. We searched The Cochrane Library, MEDLINE, EMBASE, and International Pharmaceutical Abstracts from inception to July 2011. The ClinicalTrials.gov website was searched for references to trials of febuxostat. Our search did not include any restrictions.. Two authors independently reviewed the search results and disagreements were resolved by discussion. We included any controlled clinical trial or open label trial (OLT) using febuxostat at any dose.. Data and risk of bias were independently extracted by two authors and summarised in a meta-analysis. Continuous data were expressed as mean difference and dichotomous data as risk ratio (RR).. Four randomised trials and two OLTs with 3978 patients were included. Risk of bias differed by outcome, ranging from low to high risk of bias. Included studies failed to report on five to six of the nine outcome measures recommended by OMERACT. Patients taking febuxostat 120 mg and 240 mg reported more frequent gout flares than in the placebo group at 4 to 28 weeks (RR 1.7; 95% CI 1.3 to 2.3, and RR 2.6; 95% CI 1.8 to 3.7 respectively). No statistically significant differences were observed at 40 mg and 80 mg. Compared to placebo, patients on febuxostat 40 mg were 40.1 times more likely to achieve serum uric acid levels < 6.0 mg/dL at 4 weeks (95% CI 2.5 to 639), with an absolute treatment benefit of 56% (95% CI 37% to 71%). For febuxostat 80 mg and 120 mg, patients were 68.9 and 80.7 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit compared to placebo (95% CI 13.8 to 343.9, 95% CI 16.0 to 405.5), respectively; with an absolute treatment benefit of 75% and 87% (95% CI 68 to 80% and 81 to 91%), respectively. Total discontinuation rates were significantly higher in the febuxostat 80 mg group compared to placebo (RR 1.4; 95% CI 1.0 to 2.0, absolute risk increase 11%; 95% CI 3 to 19%). No other differences were observed.When comparing allopurinol to febuxostat at 24 to 52 weeks, the number of gout flares was not significantly different between the two groups, except for febuxostat 240 mg (RR 2.3; 95% CI 1.7 to 3.0). Patients on febuxostat 40 mg showed no statistically significant differences in benefits or harms. Patients on febuxostat 80 mg and 120 mg were 1.8 and 2.2 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit (95% CI 1.6 to 2.2, 95% CI 1.9 to 2.5) with an absolute treatment benefit of 29% and 44% (95% CI 25% to 33%, 95% CI 38% to 50%), respectively, at 24 to 52 weeks. Total discontinuation rates were higher for febuxostat 80 mg and 120 mg compared to allopurinol (RR 1.5; 95% CI 1.2 to 1.8, absolute risk increase 11%; 95% CI 6% to 16%; and RR 2.6; 95% CI 2.0 to 3.3, absolute risk increase 20%; 95% CI 3% to 14%, respectively). Discontinuations due to adverse events were similar across groups. Total adverse events were lower for febuxostat 80 mg and 120 mg compared with allopurinol (RR 0.93; 95% CI 0.87 to 0.99, absolute risk increase 6%; 95% CI 0.7% to 11%; and RR 0.90; 95% CI 0.84 to 0.96, absolute risk increase 8%; 95% CI 3% to 13%, respectively). No other relevant differences wer. Although the incidence of gout flares requiring treatment may be increased in patients taking febuxostat compared to placebo or allopurinol during early treatment, no such increase in gout flares was observed in the long-term follow-up study when compared to allopurinol. Febuxostat at any dose was shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and reducing serum uric acid levels in the period from baseline to final visit when compared to placebo and to allopurinol. However, the grade of evidence ranged from low to high, which indicates that further research is needed.

Topics: Allopurinol; Chronic Disease; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Randomized Controlled Trials as Topic; Thiazoles

The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. The use of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreatable gout is progressing. Additionally, advances in our understanding of the transport of uric acid in the renal proximal tubule and the inflammatory response to monosodium urate crystals are translating into potential new treatments. In this Review, we focus on the clinical trials of febuxostat. We also review results from studies of pegloticase, a pegylated uricase in development, and we summarise data for several other pipeline drugs for gout, such as the selective uricosuric drug RDEA594 and various interleukin-1 inhibitors. Finally, we issue a word of caution about the proper use of the new drugs and the already available drugs for gout. At a time of important advances, we need to recommit ourselves to a rational approach to the treatment of gout.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Drug Administration Schedule; Drug Approval; Enzyme Inhibitors; Europe; Febuxostat; Gout; Gout Suppressants; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Thiazoles; United States; United States Food and Drug Administration; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Anti-Inflammatory Agents; Colchicine; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Risk Factors; Uric Acid

The pharmacology, pharmacokinetics, clinical efficacy, and safety of febuxostat are reviewed.. Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase for the management of hyperuricemia in patients with gout. The ability of febuxostat to decrease serum uric acid production through selective inhibition of enzyme xanthine oxidase has been established in short-term Phase II and III clinical trials and long-term open-label studies. Clinical studies have revealed that febuxostat lowers serum uric acid levels more potently than allopurinol while having minimal effects on other enzymes associated with purine and pyrimide metabolism. The most frequent adverse events reported in clinical trials with febuxostat were liver function abnormalities, nausea, arthralgias, and rash. More cardiovascular thromboembolic events occurred in randomized trials in patients treated with febuxostat. Although a causal relationship has not been established, patients should be monitored for signs and symptoms of myocardial infarction and stroke. Febuxostat is available as 40- and 80-mg tablets. The recommended starting dosage is 40 mg orally once daily. If serum uric acid concentrations are not less than 6 mg/dL after two weeks, the dosage can be increased to 80 mg orally once daily. Dosage adjustments are not needed in elderly patients or patients with mild or moderate renal or hepatic impairment.. Febuxostat is efficacious as a second-line therapy in lowering serum uric acid levels in patients with gout. Febuxostat may be an alternative for patients with gout who are unable to take allopurinol due to hypersensitivity, intolerance, or lack of efficacy.

Topics: Allopurinol; Animals; Chronic Disease; Clinical Trials as Topic; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Thiazoles; Xanthine Oxidase

In France, colchicine remains the standard treatment for the acute flare of gout. The lowest dose currently used decreases digestive toxicity. Doses of colchicine should be adapted to renal function and age, and possible drug interactions should be considered. Non steroidal anti-inflammatory drugs are an alternative to colchicine, but their use is frequently limited by comorbidity. When these treatments are contraindicated, corticosteroid injections can be performed after excluding septic arthritis. Systemic corticosteroids could be used in severe polyarticular flares. Anti-IL1 should provide a therapeutic alternative for severe cortico dependant gout with tophus. To prevent acute flares and reduce tophus volume, uric acid serum level should be reduced and maintained below 60mg/L (360μmol/L). To achieve this objective, it is often necessary to increase the daily dose of allopurinol above 300mgs, but the need to adapt the dose to renal function is a frequent cause of therapeutic failure. In the absence of renal stone or renal colic and hyperuraturia, uricosuric drugs are the second-line treatment. Probenecid is effective when creatinine clearance is superior to 50mL/min Benzbromarone, which was withdrawn due to hepatotoxicity, can be obtained on an individualized patient basis in the case of failure of allopurinol and probenecid. Febuxostat, which was recently approved, is a therapeutic alternative. Diuretics should be discontinued if possible. Use of fenofibrate should be discussed in the presence of dyslipidemia and losartan in patient with high blood pressure. Uricolytic drugs (pegloticase), which are currently being investigated, may be useful for the treatment of serious gout with tophus, especially in the presence of renal failure. Education of patient, identification and correction of cardiovascular risk factors should not be forgotten.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Thiazoles; Uric Acid; Uricosuric Agents

Gout is an inflammatory arthritis that typically presents as acute onset, recurrent, monoarticular pain. In most patients, management of pain, risk assessment for future flares, and disability is not optimal and diagnostic and management approaches are applied inconsistently. Obtaining an accurate patient history, including comorbidities, concomitant medications, and familial history, is important for optimal results. Recognizing the acute flare in the patient at risk and establishing a definitive diagnosis of gout should be conducted promptly. Therapeutic options appropriate for treating the acute flare include colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids. After flare remission, prophylaxis with a flare prevention medication, such as colchicine, should be administered followed by initiation of urate-lowering therapy with allopurinol or febuxostat. Patient education, especially counseling on risk factors and contributors to hyperuricemia and gout, can improve the likelihood of successful therapy for this often suboptimally managed disease.

Topics: Allopurinol; Anti-Inflammatory Agents; Colchicine; Diet; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Patient Education as Topic; Quality of Life; Risk Factors; Thiazoles

Topics: Allopurinol; Enzyme Activation; Febuxostat; Gout; Gout Suppressants; Humans; Randomized Controlled Trials as Topic; Thiazoles; Uric Acid; Xanthine Oxidase

Topics: Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Primary Health Care; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

Chronic hyperuricemia and acute arthritis in severe gouty patients can be difficult to manage, in particular in patients with renal failure or with history of cardio vascular conditions. Hopefully, new drugs have been approved or will emerge, and will help to overcome these situations. Febuxostat has been recently approved in France for the treatment of chronic hyperuricemia in conditions where urate deposition has already occurred. Febuxostat is a novel non-purine, selective inhibitor of xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment appears to be necessary in patients with mild-to-moderate renal impairment. Other novel hypouricemic drugs are the PEG-uricase (pegloticase), recently approved by the FDA, and a novel uricosuric drug (RDEA594), which is currently under development. The discovery that interleukin 1β (IL- β) plays a key role in the pathogenesis of acute attacks of gout has prompted to assess the efficacy of IL-1 β blockers in patients with acute gout. Biologic agents that inhibit IL-1 β such as canakinumab, rilonacept and anakinra have shown promising results for the treatment of gouty arthritis.

Topics: Allopurinol; Controlled Clinical Trials as Topic; Drug Approval; Drugs, Investigational; Febuxostat; Gout; Gout Suppressants; Humans; Interleukin-1beta; Organic Anion Transporters; Polyethylene Glycols; Recombinant Proteins; Thiazoles; Urate Oxidase

Compared to other chronic inflammatory diseases, gout appears to based on a rather "simple" pathophysiology and therefore the amount of teaching time in medical school and during internship is rather limited. On the other hand, several problems in short- and long-term management still need to be solved - combined with the problem of an increased incidence in elderly people. However, there is significant advance in the knowledge of its pathophysiology including the fact that gout is more than a pure "crystal arthopathy" but rather within the spectrum of chronic inflammatory immunologic diseases. This includes cytokines such as interleukin-1 and intracellular signaling via the inflammasome. For treatment, the novel and effective xanthine oxidase inhibitor febuxostat has been added to the therapeutic armamentarium. Guidelines of EULAR and BSR support the physician in the long-term management of the numerous gout patients.

Topics: Allopurinol; Arthritis, Gouty; Benzbromarone; Combined Modality Therapy; Cytokines; Europe; Febuxostat; Gout; Gout Suppressants; Guideline Adherence; Humans; Inflammasomes; Interleukin-1; Long-Term Care; Probenecid; Signal Transduction; Thiazoles; Uric Acid

Many patients with acute gout (11%-49%) have normal serum uric acid (SUA) levels.

Topics: Acute Disease; Allopurinol; Arthritis, Gouty; Biomarkers; Gout; Gout Suppressants; Humans; Hyperuricemia; Practice Guidelines as Topic; Uric Acid

Topics: Allopurinol; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Chondrocalcinosis; Comorbidity; Diabetes Mellitus, Type 2; Febuxostat; Gout; Gout Suppressants; Guideline Adherence; Humans; Hypertrophy, Left Ventricular; Hyperuricemia; Interleukin 1 Receptor Antagonist Protein; Kidney Failure, Chronic; Thiazoles; Xanthine Oxidase

The prevalence of gout increases with age. Up to 7% of men > 65 and 3% of women > 85 have gout. Risk of gout increases significantly with increasing serum uric acid levels. Alcohol consumption and purine-rich foods such as red meat and seafood increase the risk of incident gout significantly. Loop and thiazide diuretics are also associated with increased risk. Gout is frequently associated with the metabolic syndrome. Dehydration, increasing creatinine levels, and surgery are also known to precipitate flares. Acute gout manifests as severe joint pain, of rapid onset, reaching maximal intensity within a few hours. Gout has a predilection for lower extremity joints. It often starts at the first metatarsophalangeal joint, a condition termed podagra. Other common sites of gouty flares include: tarsal and subtalar joints; ankle; knee; wrist; small joints of the hands; Achilles tendon; and olecranon bursae. The joint affected is usually hot, red, swollen and very painful. This is often associated with skin erythema. Identification of MSU crystals in the synovial fluid of an inflamed joint or from tophi allows a definite diagnosis of gout to be made. Hyperuricaemia does not confirm or exclude gout as most people with hyperuricaemia are asymptomatic, while serum uric acid levels tend to decrease during acute attacks. Short-acting NSAIDs should be used at maximal dose as first drug of choice if not contraindicated. In patients at risk of GI complications, co-prescription of a proton pump inhibitor or the use of COX-2 selective agents should be considered. Colchicine can be particularly useful in patients with heart failure in whom NSAIDs are contraindicated but should be avoided in patients with severe renal impairment. Joint aspiration and injection of intra-articular steroids is one of the most effective ways of treating acute monoarthritic gout. Uric acid lowering therapy is initiated if a patient suffers two or more attacks in one year. Many rheumatologists will start this therapy in hyperuricaemic patients whose first attack is very severe or in polyarticular gout.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Gout; Gout Suppressants; Humans; Primary Health Care; Risk Factors; Secondary Prevention; Uric Acid

To summarize new knowledge on approved and emerging drugs used to treat hyperuricemia or the clinical manifestations of gout.. Results of several clinical trials provide new data on the efficacy and safety of the approved urate-lowering drugs, allopurinol and febuxostat. New recommendations have been presented on appropriate dosing of colchicine for acute gout flares and potential toxicities of combining colchicine with medications such as clarithromycin. Emerging therapies, including pegloticase, the uricosuric agent RDEA596, and the interleukin-1 inhibitors, rilonacept and canakinumab, have shown promise in early and late phase clinical trials.. Recent publications demonstrate an opportunity to use existing gout therapies more effectively in order to improve both efficacy and safety. Emerging therapies for gout show promise for unmet needs in selected gout populations.

Topics: Allopurinol; Clinical Trials as Topic; Colchicine; Drug Therapy, Combination; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Recombinant Fusion Proteins; Thiazoles; Uricosuric Agents

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than "standard dosage" allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.

Topics: Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Thiazoles; Treatment Outcome; Xanthine Oxidase

Generalist physicians, specifically general internists and primary care physicians, are often the first to see patients with gout and therefore play a critical role in the diagnosis and management of these patients. The aim of this review is to aid generalist physicians in diagnosing and treating gout. A case report example is presented to highlight some of the problems in diagnosing and treating gout. Practical practice points are also highlighted.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans; Male; Middle Aged; Physicians, Family; Synovial Fluid; Uric Acid

This position paper aims to clarify the presumed place of febuxostat in the management of gout patients. Since this novel xanthine oxidase inhibitor is now available, an international group of gout experts decided to formulate an international consensus statement. This statement presents the place for this new xanthine oxidase inhibitor in the treatment of gout which may contribute to optimize treatment of gout patients in Europe and worldwide.

Topics: Febuxostat; Gout; Gout Suppressants; Humans; International Cooperation; Thiazoles; Treatment Outcome; Xanthine Oxidase

Gout is a common, painful, and often debilitating rheumatologic disorder that remains one of the few arthritic conditions that can be diagnosed with certainty and cured with appropriate therapy. Allopurinol is the most frequently prescribed agent for gout in the United States. Unfortunately, most patients treated with allopurinol do not achieve target serum uric acid (sUA) levels, possibly due to a perceived intolerability to allopurinol in doses above 300 mg and the need for reduced doses in patients with renal insufficiency. Febuxostat, an orally administered, nonpurine inhibitor of xanthine oxidase, was recently approved by the U.S. Food and Drug administration for chronic management of hyperuricemia in patients with gout. Patients treated with febuxostat achieve rapid and substantial reductions in sUA levels. Compared with allopurinol-treated patients, patients receiving febuxostat 80 mg/day were more likely to achieve sUA concentrations less than 6 mg/dl. In long-term studies (up to 5 yrs), febuxostat demonstrated sustained reductions in sUA levels, nearly complete elimination of gout flares, and a frequency of adverse effects comparable to allopurinol. The most commonly reported adverse effects were liver function abnormalities, rash, nausea, and arthralgias. The recommended starting dose of febuxostat is 40 mg/day, which may be increased to 80 mg/day after 2 weeks if patients do not achieve sUA levels less than 6 mg/dl. Dosage adjustment in mild-to-moderate renal insufficiency is unnecessary; however, data are lacking on the safety of febuxostat in patients with severe renal impairment. Although more costly than allopurinol, febuxostat appears to be an acceptable alternative for the treatment of gout and hyperuricemia, and may be advantageous in patients with renal impairment, intolerance to allopurinol, or the inability to attain sUA levels less than 6 mg/dl despite adequate therapy with available agents.

Topics: Clinical Trials as Topic; Drug Interactions; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Models, Biological; Thiazoles; Xanthine Oxidase

The basic concepts of the pathogenesis and management of gout have not altered for many years. Monosodium urate monohydrate crystals drive the disease and identification of these crystals is required for certain diagnosis. In contrast, our understanding of the mediators of gouty inflammation, the appropriate target serum urate concentration during treatment, the drugs available and the best ways to use those drugs have all advanced in recent years and will be the focus of this review.

Topics: Allopurinol; Animals; Biomarkers; Disease Management; Gout; Humans; Uric Acid

The prevalence of gout in the western countries is 1-2%. The disease has become more common during the last two decades, and the same time its clinical picture has changed. The disease is often polyarticular, the patients are older than before and they have more often associated cardiovascular diseases and renal insufficiency. Effective treatment of acute gout is nonsteroidal anti-inflammatory drugs with intra-articular or systematic corticosteroids. The goal for the treatment of intermittent and chronic gout is to maintain serum urate concentration velow 360 micromol/l by diet and by antihyperuricemic meditation, primarly allopurinole and probenecid. Febuxostat is a new xanthine oxidase inhibitor, which will be available for the treatment of refractory gout in the near future. Special attention should be paid on detecting and treating cardiovascular diseases and their risk factors in patients with gout.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Diet; Febuxostat; Gout; Gout Suppressants; Humans; Probenecid; Risk Factors; Thiazoles; Uricosuric Agents

Gout is an acute inflammatory arthritis with the potency to fully destroy the integrity of the joint leading to severe disability. Besides joint destruction, gout is often associated with an accelerated atherosclerosis culminating in an increased risk of cardiovascular disease. The current existing therapy modalities allow an efficient treatment that not only controls local inflammation but might also have an effect on the generalised features that surround this condition. Here we discuss the modes of clinical appearance, how we are nowadays supposed to treat gout and the current knowledge about the pathogenesis of this clinical syndrome.

Topics: Aged; Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Risk Factors; United States; Uric Acid

In a previous issue of the journal, Becker and colleagues present efficacy and safety data from a large study comparing febuxostat to allopurinol. The study showed non-inferiority of febuxostat 40 mg/day in lowering serum urate compared to allopurinol 200 to 300 mg/day. More importantly, the study showed a similar frequency of important cardiovascular adverse events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) for febuxostat 40 mg/day (0%), febuxostat 80 mg/day (0.4%) and allopurinol groups (0.4%). Other cardiac adverse event rates (unstable angina, coronary revascularization, cerebral revascularization, transient ischemic attack, venous and peripheral arterial vascular thrombotic event, congestive heart failure, and arrhythmia) were also similar for febuxostat 40 mg/day (1.3%), febuxostat 80 mg/day (1.2%) and allopurinol groups (0.9%). A meta-analysis of safety data from published studies is presented.

Topics: Allopurinol; Clinical Trials as Topic; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles

Gout is a common disease and the prevalence is increasing. Chronic hyperuricemia (uric acid serum levels >6.8 mg/dL) is a key feature. Treating to a target uric acid level of 6.0 mg/dL is recommended. In addition to cochicine, probenecid, and allopurinol, feboxostat is a new option for urate-lowering therapy.

Topics: Allopurinol; Antimetabolites; Chronic Disease; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Probenecid; Thiazoles; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Benzbromarone; Colchicine; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Metabolic Syndrome; Practice Guidelines as Topic; Probenecid; Uricosuric Agents

Many patients with gout have comorbidities, including hypertension and chronic kidney disease (CKD). The goals when treating gout are no different in these patients, but the choice and dosage of drugs may need to be modified.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Comorbidity; Disease Progression; Febuxostat; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Risk Factors; Thiazoles

Hyperuricemia is an elevated uric acid level in blood. Gout is a common systemic metabolic disease characterized by deposition of monosodium urate monohydrate crystals with resultant acute intense inflammation of the involved joint. The clinical spectrum ranges from asymptomatic hyperuricemia to intermittent acute episodes of gouty arthritis to chronic tophaceous gout and chronic gouty arthropathy.

Topics: Anti-Inflammatory Agents; Gout; Gout Suppressants; Humans; Hyperuricemia; Risk Factors; Uricosuric Agents; Xanthine Oxidase

Allopurinol, the first-line drug for serum urate-lowering therapy in gout, is approved by the US Food and Drug Administration for a dose up to 800 mg/d and is available as a low-cost generic drug. However, the vast majority of allopurinol prescriptions are for doses < or = 300 mg/d, which often fails to adequately treat hyperuricemia in gout. This situation has been promoted by longstanding, non-evidence-based guidelines for allopurinol use calibrated to renal function (and oxypurinol levels) and designed, without proof of efficacy, to avoid allopurinol hypersensitivity syndrome. Severe allopurinol hypersensitivity reactions are not necessarily dose-dependent and do not always correlate with serum oxypurinol levels. Limiting allopurinol dosing to < or = 300 mg/d suboptimally controls hyperuricemia and fails to adequately prevent hypersensitivity reactions. However, the long-term safety of elevating allopurinol dosages in chronic kidney disease requires further study. The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.

Topics: Allopurinol; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Hypersensitivity; Gout; Gout Suppressants; Health Care Costs; Humans; Hyperuricemia; Kidney; Kidney Function Tests; Oxypurinol; Practice Guidelines as Topic

Significant pain, activity limitation, and disability in patients with acute and chronic gouty arthritis lower health-related quality of life. Although many effective therapies are available for gouty arthritis, medication errors are common. One goal of therapy is to reduce the frequency of gout flares by lowering serum uric acid. Further, evidence suggests that the quality of care provided to patients with gout may also impact health-related quality of life. This article reviews evidence concerning quality of care and quality of life for patients with gout.

Topics: Allopurinol; Delivery of Health Care; Disability Evaluation; Female; Gout; Gout Suppressants; Health Status; Humans; Male; Medication Errors; Outcome Assessment, Health Care; Practice Guidelines as Topic; Predictive Value of Tests; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Uric Acid

To discuss currently available urate-lowering therapeutic options for gout in the United States and newer therapeutic initiatives in development.. Currently available urate-lowering drugs include allopurinol and probenecid. These drugs are effective but are often underdosed or underutilized, and caution must be taken in patients with multiple comorbidities. Newer therapeutic agents in development include febuxostat, a nonpurine analogue xanthine oxidase inhibitor, and pegloticase, a pegylated recombinant uricase.. There have been no new US Food and Drug Administration-approved urate-lowering drugs for gout in the past 40 years. Recent advances in therapeutics promise to provide the opportunity for much needed improvement in patient outcomes in this disorder.

Topics: Allopurinol; Drug Discovery; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Thiazoles; United States; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. In two Phase III trials, significantly more febuxostat-treated gout patients met the primary endpoint [serum urate (sUA) <6 mg/dl (<360 mumol/l) at the last three visits] (48 and 53% with 80 mg; 65 and 62% with 120 mg), compared with those receiving allopurinol 300 mg (22 and 21%; P < 0.001 in both studies). Febuxostat was more effective than allopurinol in the subset with impaired renal function; no dose adjustment is required in mild-to-moderate renal impairment. Long-term extension studies confirmed the efficacy and tolerability of febuxostat. In patients who achieved the sUA target of 6 mg/dl (360 mumol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects (Antiplatelet Trialists Collaboration events) was numerically higher with febuxostat than with allopurinol, but this was not statistically significant. Co-administration of febuxostat with AZA or 6-mercaptopurine is not recommended. Prophylaxis (colchicine and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, febuxostat is more effective than allopurinol 300 mg daily in reducing sUA levels <6 mg/dl (360 mumol/l), the target recommended by EULAR, and offers a new option for the long-term treatment of gout.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Randomized Controlled Trials as Topic; Thiazoles

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of febuxostat for the management of hyperuricaemia in patients with gout based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two randomised controlled trials comparing the efficacy and safety of febuxostat with allopurinol. The trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. A pooled clinical efficacy analysis showed that a daily dose of 80 mg or 120 mg of febuxostat was significantly more effective than fixed-dose allopurinol (300/100 mg/day) at lowering serum uric acid (sUA) levels to therapeutic targets (< 6 mg/dl); however, a large percentage of febuxostat patients did not achieve the primary end point and the fixed-dose allopurinol regimen may have introduced bias. There were no differences between treatments in more clinically important outcomes such as gout flares and tophi resolution after 52 weeks of treatment. No subgroup analyses were conducted for patients with renal impairment, non-responders to allopurinol or patients with severe disease. Supplementary data from a 2-year open-label extension study were also provided, but were difficult to interpret and poorly reported. The incidence of adverse events was similar between treatments, although more febuxostat recipients discontinued treatment prematurely. A decision tree model was developed to determine the cost-effectiveness of febuxostat. The scope was limited to the comparison of continual febuxostat treatment with continual allopurinol treatment. Switching between treatments or withdrawing treatment in patients whose sUA levels had not decreased was not permitted. The model predicted a cost-effectiveness of 16,324 pounds [95% confidence interval (CI) 6281 pounds to 239,928 pounds] per quality-adjusted life-year (QALY) gained for febuxostat compared with allopurinol after 2 years of treatment. The incremental cost per QALY was below 20,000 pounds in 63% of the simulations undertaken. Changes in the time horizon did not materially affect the results. The ERG believes that the modelling structure employed was not appropriate to estimate the cost-effectiveness of febuxostat within a treatment algorithm. In addition, there were concerns about the methodolog

Topics: Allopurinol; Cost-Benefit Analysis; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Randomized Controlled Trials as Topic; Thiazoles

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Probenecid; Treatment Failure; Urate Oxidase

Febuxostat, a nonpurine selective inhibitor of both the oxidized and reduced forms of xanthine oxidase, was approved in February 2009 by the US Food and Drug Administration for the management of hyperuricemia in adults with gout.. The purpose of this review was to summarize available information about the clinical use of febuxostat, including its chemistry, pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile.. A search of the medical literature using PubMed (1949-August 2009) and the Iowa Drug Information Service (1966-August 2009) was performed to identify all published articles about febuxostat. Key search terms included febuxostat, hyperuricemia, gout, TMX-67, and TEI-6720. Articles were limited to those published in English. Reference lists of the primary set of articles identified were reviewed for pertinent articles and scientific meeting abstracts not identified in the original search.. A total of 88 published articles (including 14 human studies) were identified in the original search. Review of the references of these 88 articles yielded 7 additional trials published in abstract form. Clinical trial data from this review were obtained from these 21 studies. Dose-dependent reductions from baseline in serum urate occur with febuxostat. Clinical trials found that 40 mg/d of febuxostat was noninferior to conventionally dosed allopurinol (300 mg/d) in the percentage of subjects achieving the primary end point of serum urate <6.0 mg/dL (45% for febuxostat vs 42% for allopurinol), whereas 80 mg/d of febuxostat was reported to be superior (67% vs 42%; P < 0.001). Febuxostat 40 and 80 mg/d appeared to be well tolerated in the populations studied, with adverse events mostly limited to liver enzyme elevations (6.6% and 4.6%, respectively), nausea (1.1% and 1.3%), arthralgias (1.1% and 0.7%), and rash (0.5% and 1.6%). Febuxostat does not require dosage adjustment in patients with mild to moderate renal impairment (creatinine clearance, 30-89 mL/min). Because of the risk of acute gout flares occurring when febuxostat treatment is initiated, concomitant therapy with colchicine or an NSAID for >or=8 weeks is recommended.. Febuxostat is the first agent marketed in the United States to treat hyperuricemia of gout since allopurinol was approved in 1964. In English-language published clinical trials, it was found to be noninferior to allopurinol and generally well tolerated.

Topics: Allopurinol; Biotransformation; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Half-Life; Humans; Hyperuricemia; Thiazoles; Tissue Distribution; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Hyperuricemia; Uricosuric Agents; Xanthine Oxidase

Gout is currently the most common form of inflammatory arthritis in men. The overall incidence of gout has increased rapidly in the past 20 years. Clinicians in all fields are likely to experience a patient with acute gout in their career. Uncontrolled gout and hyperuricemia can lead to joint destruction and significant morbidity. Fortunately, these diseases can be readily treated and long-term sequelae can be prevented. Recent advances in understanding the role of the innate immune system in acute gout have provided new treatment options. This article addresses the epidemiology, inflammatory pathophysiology, pain management techniques (including recent advances), and treatment of the underlying disease itself.

Topics: Adrenal Cortex Hormones; Allopurinol; Animals; Disease Management; Gout; Humans; Pain

The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem.. Refractory gout refers to those patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl. Patients with refractory gout have reduced quality of life, functional impairment, and joint destruction. Multiple factors contribute to refractory gout, and they often relate to delayed or insufficient dosing with allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel xanthine oxidase inhibitor, represents a potential alternative to allopurinol in refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric acid into allantoin, is showing promise with its ability to rapidly diminish serum urate levels. The recently defined role of the NALP3 inflammasome in the inflammatory phase of gout suggests a potential role for interleukin-1 inhibition in urate crystal-induced inflammation.. Refractory gout occurs when urate levels are not adequately controlled. Emerging therapies may improve the clinical course of patients with recalcitrant disease.

Topics: Allopurinol; Anti-Inflammatory Agents; Gout; Humans; Inflammation; Treatment Failure; Urate Oxidase; Uricosuric Agents

Gout is a crystal deposition disease. European and Japanese guidelines of management for gout recommend that serum urate concentration should be maintained below 6.0 mg/dL to promote crystal dissolution leading to prevention of recurrent gouty attack. Although allopurinol is recommended to be an adequate drug for urate lowering therapy in all gouty patients by European guideline, it is desirable that allopurinol is indicated in patients with overproduction type and benzbromarone in patients with underexcretion type, recommended by Japanese guideline. Asymptomatic hyperuricemia dose not equate to gout. As there is no evidence to support treatment of isolated hyperuricemia with urate lowering therapy currently, it is difficult to establish lowering goal of serum urate level in patients with asymptomatic hyperuricemia. Advice regarding lifestyle and treatment of associated comorbidity should be preferred to urate lowering therapy. However, urate lowering therapy may be indicated in high risk patients with hyperuricemia who are suffered from hypertension, diabetes mellitus, ischemic heart disease and renal insufficiency.

Topics: Allopurinol; Benzbromarone; Cardiovascular Diseases; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Patient Care Planning; Practice Guidelines as Topic; Renal Insufficiency; Uric Acid

Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.

Topics: Allopurinol; Benzbromarone; Gout; Humans; Hyperuricemia; Kidney Tubules, Proximal; Organic Anion Transporters; Organic Cation Transport Proteins; Uric Acid; Uricosuric Agents

Inhibitors of xanthine oxidoreductase decrease production of uric acid, thus they act as hypouricemic drugs. Allopurinol, a prototypical xanthine oxidoreductase inhibitor, has been widely prescribed for treatment of gout and hyperuricemia. However, severe side effects of allopurinol may occur in patients with renal insufficiency. Recently, novel nonpurine selective inhibitors of xanthine oxidoreductase have been developed as potential alternatives to allopurinol. They have different inhibition mechanisms, utilizing the enzyme structure and the reaction mechanism. Such variation of the inhibition mechanism affects/in vivo/hypouricemic effects of the inhibitors.

Topics: Allopurinol; Drug Design; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Nitriles; Pyrazoles; Pyridines; Thiazoles; Xanthine Dehydrogenase

Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. To critically review the clinical trial data, safety profile, pharmacology, and role of febuxostat for the treatment of hyperuricemia and gout. A review of the literatures on febuxostat was performed. All available human studies describing the pharmacology of febuxostat were included; including pharmacodynamics, efficacy, and safety of febuxostat. Available studies, patents and abstracts were identified through PubMed (1990-December 2006), Delphion, Cochrane Databases, and the American College of Rheumatology and European League Against Rheumatism Web sites. Key search terms were febuxostat, TMX-67, and TEI-6720. Febuxostat has been used at a dose of 80 to 120 mg for the management of hyperuricemia in gout. The drug is mainly metabolized by the liver and therefore mild-moderate renal impairment does not appear to impede its effect. However, given the limited long-term liver function safety data, failure of a large percentage of patients taking febuxostat to achieve the primary end point of serum urate levels less than 6.0 mg/dL, and higher drop out rate in the Febuxostat group in the clinical trials, the exact role of febuxostat as a urate-lowering therapy remains uncertain. Febuxostat is a promising alternative to allopurinol for the treatment of gout and hyperuricemia. The optimal length of colchicines prophylactic therapy for chronic gout, clinical significance of abnormal liver function tests results during therapy, and safety in patients with moderate or severe hepatic and renal insufficiency warrant further investigation. A post-market surveillance is also needed to address the safety issue of long-term febuxostat treatment.

Topics: Animals; Clinical Trials as Topic; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Patents as Topic; Thiazoles; Xanthine Oxidase

The purpose of this review is to highlight the recent developments in the management of gout.. Guidelines for the diagnosis and management of gout from EULAR, quality of care indicators, and outcome measures for clinical trials have been published. The standards of gout diagnosis and management are very low. Allopurinol remains the mainstay for serum uric acid lowering therapy. In an important percentage of patients receiving allopurinol, serum uric acid levels are insufficient to promote crystal dissolution. Febuxostat, a new serum uric acid lowering drug, has shown good results. Information on uricase continues to appear. For treatment of gouty inflammation, etoricoxib (a new cyclooxygenase 2 inhibitor) has been shown to be as effective as indomethacin. Finally, the association of gout with the metabolic syndrome and its comorbidities, and the newly described association of gout with myocardial infarction, bring lifestyle and dietary modifications to the front in the management of gout.. Proper gout management requires changes to the physician's attitude towards the disease; essentially: (1) an unequivocal diagnosis based in urate crystal identification, (2) a clearly settled aim of the treatment: crystal elimination from the joints and elsewhere, and (3) proper use of the available therapeutic alternatives. Promoting a proper lifestyle appears to be especially important.

Topics: Allopurinol; Feeding Behavior; Gout; Humans; Metabolic Syndrome; Risk Reduction Behavior; Uric Acid; Uricosuric Agents

The majority of patients with gout are cared for by primary care physicians. Although both the physician and patient may easily recognize the acute arthritis of gout, errors in selecting the most appropriate medication and proper dose are common. The clinical stages of gout include asymptomatic hyperuricemia, intermittent gouty arthritis, and chronic tophaceous gout. Treatment of gout is usually considered after the first attack of arthritis, typically podagra. The aims of treatment are to alleviate the pain and inflammation associated with acute attacks, prevent future attacks, and decrease uric acid levels. Confusion frequently arises because certain medications such as colchicine may have dual purposes: to treat an acute attack and to suppress future attacks. The purpose of this management update is to provide practical advice about prescribing the proper medication considering both treatment goals and patient comorbidities.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Chronic Disease; Colchicine; Drug Therapy, Combination; Family Practice; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Pain Measurement; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Uric Acid

Since the original recognition of these conditions in 1961, a great deal has been learned about the pathogenesis, clinical manifestations, and appropriate treatment of gout and pseudogout, and the role of crystals in osteoarthritis has been further defined. The variable manifestations of crystal-induced arthritis in elderly populations has led to a greater need for proper diagnosis and treatment strategies for these increasingly common forms of arthritis.

Topics: Aged; Allopurinol; Arthritis; Arthritis, Gouty; Calcium Pyrophosphate; Chondrocalcinosis; Comorbidity; Diagnosis, Differential; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperuricemia; Osteoarthritis; Renal Insufficiency; Uric Acid

Gout is the most frequent cause of man's inflammatory arthritis after forty years of age and its prevalence is increasing. Although the physiopathology of this condition is starting to be thoroughly recognized, therapeutic approaches have not fundamentally changed during the last decades. In the absence of renal or digestive contraindications, non steroidal inflammatory drugs are the treatment of choice for acute flares of gout arthritis. If an indication for urate-lowering therapy exists, a xanthine oxydase inhibitor or an uricosurical treatment remains the treatment of choice, depending on the patient's co-morbidity. Purine restrictive diet, weight loss in case of obesity and lower alcohol intake are highly necessary co-measures.

Topics: Diet; Gout; Gout Suppressants; Humans; Xanthine Oxidase

Successful management of chronic gout depends on reducing body pools of urate. The benchmark of success is to maintain serum urate levels at less than 6 mg/dL using therapies such as probenecid or allopurinol. In a subset of patients with gout, these medications fail to achieve this benchmark, resulting in ongoing signs and symptoms characteristic of treatment-failure gout. Potential therapies now in clinical development show promise for treating this refractory patient population. In this article, we review the clinical characteristics associated with treatment-failure gout and discuss recent data from clinical trials of febuxostat and uricase.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiazoles; Treatment Failure; Urate Oxidase; Uric Acid

Topics: Allopurinol; Gout; Humans; Treatment Outcome; Uric Acid

In the acute stage of gout, the hallux is most commonly involved followed by the mediotarsal joints and the Achilles tendons. Diagnosis of gout is established when typical monosodium urate crystals can be identified. Apart from NSAIDs, colchicine can be used when there is no renal impairment. Hypouricemic agents (allopurinol or uricosuric drugs) must be initiated one or two weeks after the acute attack of gout because there are risks of exacerbation. Losartan as well as fenofibrate have uricosuric properties. Chondrocalcinosis of the foot can be observed in hemochromatosis. Diffuse idiopathic skeletal hyperostosis (DISH) can cause severe talagia. Hypercholesterolemia can induce xanthomas of the Achilles tendons. Apatite rheumatism can be observed in chronic dialysis patients.

Topics: Achilles Tendon; Acute Disease; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Apatites; Chondrocalcinosis; Colchicine; Fenofibrate; Foot Diseases; Gout; Gout Suppressants; Hallux; Hemochromatosis; Humans; Hypercholesterolemia; Hyperostosis, Diffuse Idiopathic Skeletal; Hypolipidemic Agents; Losartan; Radiography; Renal Dialysis; Time Factors; Xanthomatosis

A 71-year-old Cambodian man who was commenced on allopurinol for the treatment of gout developed a generalized papulopustular follicular eruption 8 weeks following introduction of the drug. The skin biopsy findings were consistent with that of eosinophilic pustular folliculitis. Resolution of the rash took place during the 8 weeks following cessation of allopurinol and treatment with oral and topical corticosteroids.

Topics: Administration, Oral; Aged; Allopurinol; Diagnosis, Differential; Drug Eruptions; Folliculitis; Gout; Gout Suppressants; Humans; Male

To review the pharmacology, pharmacokinetics, clinical trial data, safety profile, precautions, and place in therapy of febuxostat, a novel nonpurine xanthine oxidase inhibitor in development for the treatment of hyperuricemia and gout.. Available studies and abstracts were identified through MEDLINE (1990-November 2006), Science Citation Index, International Pharmaceutical Abstracts, Cochrane Databases, and the American College of Rheumatology and European League Against Rheumatism Web sites. Key search terms were febuxostat, TMX-67, TEI-6720, hyperuricemia, and gout.. All available studies describing the pharmacology of febuxostat were included. Human studies formed the basis for discussion of clinical parameters, including pharmacokinetics, pharmacodynamics, efficacy, and safety of febuxostat.. Febuxostat significantly reduces uric acid levels within 2 weeks after initiation of therapy and up to 48% by the end of 104 weeks of therapy. Approximately 60% of patients achieved the primary goal of serum uric acid less than 6 mg/dL during the last 3 months following once-daily administration of febuxostat 80 mg or 120 mg for at least 52 weeks. The most common adverse reactions to febuxostat were abnormal results from liver function tests, diarrhea, headache, arthralgias, and musculoskeletal symptoms. Due to its potency, patients are at an increased risk of experiencing gout flares for at least the first year of therapy. Up to 70% of patients in clinical trials experienced gout flares despite concomitant prophylactic treatment with colchicine or naproxen. Additional clinical trial evidence supports the efficacy and safety of febuxostat in the treatment of hyperuricemia and gout.. Febuxostat is a promising alternative to allopurinol for the treatment of gout and hyperuricemia. The optimal length of prophylactic therapy, clinical significance of abnormal liver function tests results during therapy, and safety in patients with moderate or severe renal insufficiency warrant further investigation.

Topics: Febuxostat; Gout; Humans; Hyperuricemia; Thiazoles; Xanthine Oxidase

Topics: Allopurinol; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Diagnosis, Differential; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Prognosis; Risk Factors; Sex Factors; Time Factors; Treatment Outcome; Uric Acid

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. With febuxostat 10-120 mg, the pharmacokinetics are linear. No dose adjustment appears to be necessary in those with renal insufficiency or mild-to-moderate hepatic impairment. Febuxostat 10-120 mg/day rapidly and sustainably reduces serum uric acid by 25-70% in uric acid underexcretors and overproducers. Prophylaxis with colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare risk from the rapid urate lowering after febuxostat initiation. Febuxostat is well tolerated, the majority of treatment-related adverse events are transient and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options for urate-lowering therapy in those with gout.

Topics: Disease Management; Enzyme Inhibitors; Febuxostat; Gout; Humans; Hyperuricemia; Thiazoles; Xanthine Oxidase

Hyperuricemia is present in approximately 5% of the population, the vast majority of whom are asymptomatic and at no clinical risk. Complications, including renal calculi, uric acid nephropathy and gout, occur in a small proportion of patients. Allopurinol, an analog of hypoxanthine, has been widely used in clinical practice for over 30 years for the treatment of hyperuricemia and gout. Two percent of patients taking this medication develop a mild exanthema. A syndrome characterized by exfoliative dermatitis, hepatitis, interstitial nephritis and eosinophilia has been described previously. Termed allopurinol hypersensitivity syndrome, its etiology is related to the accumulation of one of the allopurinol metabolites, oxypurinol; clearance of oxypurinol is decreased in the setting of renal insufficiency and the use of thiazide diuretics. The term DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) was recently introduced to describe a disorder associated with various drugs or viral infections and characterized by similar features. The pathophysiology of allopurinol-induced hypersensitivity, clinical presentation and treatment are reviewed.

Topics: Allopurinol; Drug Hypersensitivity; Gout; Gout Suppressants; Humans

Gout and calcium pyrophosphate deposition disease are two common causes of inflammatory joint disease. Despite differences underlying their pathogenesis, their clinical presentation and treatment share some common features. Optimal treatment for both requires prompt resolution of acute synovitis, reduction of chronic joint damage and management of associated conditions. Available therapeutic interventions and future strategies are reviewed in this article.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Chondrocalcinosis; Colchicine; Drug Combinations; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Multicenter Studies as Topic; Probenecid; Randomized Controlled Trials as Topic; Thiazoles; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Gout is a group of diseases characterized by arthritis and results from a disturbance of urate metabolism with the deposition of monosodium urate crystals in the joints and soft tissues. Often, but not invariably, the serum urate levels are elevated as a result of overproduction or underexcretion of uric acid. Clinical manifestations include acute and chronic arthritis, tophaceous deposits, interstitial renal disease, and uric acid nephrolithiasis. The diagnosis is based on the identification of uric acid crystals in joints, tissues, or body fluids. Acute episodes are treated with colchicine, NSAIDs, or steroids. Long-term management includes treatment with uricosuric agents or xanthine oxidase inhibitors.

Topics: Adult; Age Factors; Arthritis, Gouty; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Female; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis; Prevalence; Sex Factors; Tomography, X-Ray Computed; Uricosuric Agents; Xanthine Oxidase

Although allopurinol has been available for approximately 50 years, hyperuricemia and its sequelae are not only prevalent, but the incidence and costs associated with this disorder continue to increase. However, several new therapies have been developed. Recombinant urate oxidase has been useful in the treatment of tumor lysis hyperuricemia, and pegylated urate oxidase shows promise in patients with hyperuricemia and gout. Febuxostat and Y-700 are new oral xanthine oxidase inhibitors that are in human clinical trials. Tailoring of antilipid therapy in selected hyperuricemic and hyperlipidemic patients with fenofibrate may be of benefit in lowering blood cholesterol and uric acid levels. Similarly, treatment of selected hyperuricemic patients who also are hypertensive with losartan or amlodipine may be beneficial in lowering blood pressure and hyperuricemia. Despite these advances, new treatments for hyperuricemia are needed.

Topics: Allopurinol; Amlodipine; Clinical Trials as Topic; Enzyme Inhibitors; Febuxostat; Gout; Humans; Hyperuricemia; Losartan; Pyrazoles; Thiazoles; Treatment Outcome; Urate Oxidase; Uric Acid; Xanthine Oxidase

To review the current understanding of the causes and the management of gout.. Publications on all peer-review literature from MEDLINE from 1965 to January 2004.. Selected and evaluated by the author.. Extracted and evaluated by the author.. The underlying metabolic disorder in gout is hyperuricaemia. Most patients with hyperuricaemia remain asymptomatic throughout their lifetime. The phase of asymptomatic hyperuricaemia ends with the first attack of gouty arthritis or urolithiasis. The risk of gout and stone formation is increased with the degree and duration of hyperuricaemia. Drugs available for the treatment of acute gouty arthritis, such as non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase 2 inhibitors, systemic corticosteroids, or colchicine, are effective. For periods between attacks, prophylactic therapy, such as low-dose colchicine, is effective. In those with recurrent attacks of more than two to three times yearly, a uric acid-lowering agent as a long-term therapy should be considered to avoid recurrence and the development of tophaceous gout.. Effective management of gout can be achieved through better understanding of the causes of the condition, preventive measures as well as drug treatment.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Colchicine; Cyclooxygenase Inhibitors; Diet Therapy; Female; Gout; Gout Suppressants; Heart Failure; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Purines; Xanthine Oxidase

Topics: Acute Disease; Benzothiadiazines; Diuretics; Female; Gout; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Metabolic Syndrome; Obesity; Postmenopause; Sodium Chloride Symporter Inhibitors; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Gout; Gout Suppressants; Humans; Xanthine Oxidase

The manifestations of gout can be abolished permanently by lifelong urate-lowering therapy maintaining serum urate levels under 360 mmol/l, as this ensures dissolution of pathogenic crystals of monosodium urate monohydrate. Benzbromarone has been withdrawn from the market, leaving allopurinol as the only urate-lowering drug readily available in France. Allopurinol may induce unacceptable side effects, and in patients with dose-limiting renal failure it may not be sufficiently effective. Because allopurinol can induce serious side effects when given concomitantly with purine antimetabolites, it is contraindicated in organ transplant recipients. In patients who cannot tolerate allopurinol, dietary treatment, discontinuation of diuretic agents, and use of losartan or fenofibrate to treat concomitant hypertension or dyslipidemia, respectively, may ensure adequate control of serum urate levels. Desensitization to allopurinol can be attempted in patients with mild cutaneous hypersensitivity reactions but is difficult to perform and rarely used. Uricosuric agents may be helpful in patients with normal or diminished urate excretion. Probenecid is available in France from hospital pharmacies, and benzbromarone can be prescribed via a time-limited authorization procedure. Rasburicase, an Aspergillus urate oxidase produced by genetic engineering, is indicated to prevent acute hyperuricemia induced by chemotherapy for hematological malignancies. Factors that limit the use of rasburicase include the absence of a marketing authorization, the need for parenteral administration, and the absence of validated treatment schedules. Patients with renal failure precluding the use of effective allopurinol dosages are good candidates for benzbromarone therapy. Organ transplant recipients can be given benzbromarone, within the current restrictions to its use; alternatively, mycophenolate mofetil can be substituted for calcineurin inhibitors, which elevate serum urate levels, or for azathioprine, which contraindicates the use of allopurinol.

Topics: Allopurinol; Drug Hypersensitivity; Drug Resistance; Gout; Gout Suppressants; Humans

Topics: Allopurinol; Arteriosclerosis; Benzbromarone; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Kidney Diseases; Probenecid; Prognosis; Risk; Uricosuric Agents; Urinary Calculi; Xanthine Oxidase

Topics: Allopurinol; Calcium Oxalate; Diet; Gout; Humans; Hydrogen-Ion Concentration; Hyperuricemia; Tomography, Spiral Computed; Urinary Calculi; Urine

Topics: Allopurinol; Chromosomes, Human, Pair 16; Genes, Dominant; Gout; Humans; Hyperuricemia; Kidney Diseases

Topics: Allopurinol; Glomerulonephritis; Glomerulonephritis, IGA; Gout; Humans; Hyperuricemia; Lead Poisoning; Polycystic Kidney, Autosomal Dominant

Topics: Allopurinol; Animals; Antioxidants; Arteriosclerosis; Enzyme Inhibitors; Free Radical Scavengers; Gout; Humans; Oxidative Stress; Reactive Oxygen Species; Uric Acid; Xanthine Oxidase

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Comorbidity; Enzyme Inhibitors; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperuricemia; Incidence; Risk Factors; Uricosuric Agents; Xanthine Oxidase

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged

Treatment of asymptomatic hyperuricemia is not necessary in most patients, unless perhaps they have very high levels of uric acid or are otherwise at risk of complications, such as those with a personal or strong family history of gout, urolithiasis, or uric acid nephropathy.

Topics: Age Factors; Allopurinol; Cardiovascular Diseases; Clinical Trials as Topic; Gout; Gout Suppressants; Humans; Hypoxanthine Phosphoribosyltransferase; Reference Values; Uric Acid; Urinary Calculi

Since the findings of Yü and Gutman [1], the hyperuricosuric calcium stone former is a unique clinical entity. While an impressive number of clinical and epidemiologic studies implicate hyperuricosuria in calcium stone formation, the exact physicochemical mechanism by which uric acid affects calcium oxalate crystallization has not been proven. Allopurinol decreases stone recurrences and is the drug of choice for patients with isolated HCN.

Topics: Allopurinol; Calcium Oxalate; Citrates; Female; Gout; Gout Suppressants; Humans; Kidney Calculi; Lithiasis; Male; Uric Acid

A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant patients with gout and "underexcretion" hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy- associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.

Topics: Allopurinol; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Kidney; Transplantation, Homologous; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Glucocorticoids; Gout; Gout Suppressants; Humans

Topics: Animals; Gout; Humans; Lung; NADPH Oxidases; Reactive Oxygen Species; Respiratory Distress Syndrome; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase

For the management of acute gouty arthritis, non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice. In recent years, the use of colchicine has declined because of its frequent adverse reactions, and its reduced efficacy when administered more than 24 hours after onset of an acute attack. Intra-articular corticosteroid therapy (e.g. methylprednisolone acetate) is indicated for the treatment of acute mono or oligoarticular gouty arthritis in aged patients, and in those with co-morbid conditions contraindicating therapy with either NSAIDs or colchicine. Oral corticosteroids (e.g. prednisone), and both parenteral corticotrophin (ACTH) and corticosteroids (e.g. intramuscular triamcinolone acetonide) are valuable, relatively safe alternate treatment modalities in those with polyarticular attacks. For the treatment of hyperuricaemia and chronic gouty arthritis, allopurinol is the preferred urate-lowering drug. Its toxicity in elderly individuals, those with renal impairment, and in cyclosporine-treated transplant patients can be minimised by adjusting the initial dose according to the patient's creatinine clearance. In those experiencing cutaneous reactions to allopurinol, cautious desensitisation to the drug can be achieved using a schedule of gradually increasing doses. The therapeutic usefulness of uricosuric drugs is limited by the presence of renal impairment, occurrence of intolerable side-effects, or concomitant intake of salicylates. They are particularly indicated in patients allergic to allopurinol and in those with massive tophi requiring combined therapy with both allopurinol and a uricosuric.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Gouty; Chronic Disease; Clinical Trials as Topic; Female; Gout; Gout Suppressants; Humans; Injections, Intra-Articular; Male; Middle Aged; Singapore; Treatment Outcome

Allopurinol hypersensitivity syndrome (AHS) is a severe reaction which is potentially lethal. Exanthematous rash, fever, eosinophilia, and other severe reactions such as toxic epidermal necrolysis, acute vasculitis, and severe hepatic and renal dysfunctions are manifestations of this syndrome. The authors report a case of lethal massive hepatic necrosis due to allopurinol in a patient with the asymptomatic hyperuricemia. They also describe the risk factors most frequently associated with the development of AHS and the strategy for its prevention and consequent reduction of the mortality associated with this syndrome.

Topics: Aged; Aged, 80 and over; Allopurinol; Drug Hypersensitivity; Fatal Outcome; Gout; Gout Suppressants; Humans; Liver; Male; Necrosis

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans; Uric Acid

We now have sufficient knowledge to be able to identify the factors contributing to hyperuricemia in most patients with gout. Some of these factors, such as obesity, a high-purine diet, regular alcohol consumption, and diuretic therapy, may be correctable. In patients with persistent hyperuricemia, regular medication should lower the serum urate concentration to an optimal level. The continuing challenge is to educate patients about correctable factors and the importance of regular medication and ensure their compliance so that attacks of gout do not recur.

Topics: Acute Disease; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Diet; Gout; Gout Suppressants; Humans; Purines; Steroids; Uric Acid; Uricosuric Agents; Xanthine Oxidase

The risk for renal insufficiency by uric acid precipitation in medulla of kidney correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. The patients with gout or hyperuricemia have sometimes acidic urine and increased uric acid excretion. Accordingly, these patients frequently accompany by renal insufficiency. Improvement of hyperuricosuria, increasing of urine volume, and alkalinization of urine to pH6 6.5, are effective for the prevention from renal insufficiency. Acute renal failure related to hyperuricemia, can also occured secondary to cell lysis. Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure after starting chemotherapy to cancers, especially lymphoproliferative malignancies. Administration of allopurinol 500-600 mg and adequate hydration and alkalinization of urine are advocated to prevent acute renal failure. Intensive care with hemodialysis is often required to treat renal failure, because renal failure is reversible in most cases.

Topics: Acute Kidney Injury; Allopurinol; Gout; Humans; Hydrogen-Ion Concentration; Kidney; Renal Dialysis; Tumor Lysis Syndrome; Uric Acid; Urine

A large number of pharmacological agents affect the serum concentration of uric acid. Some drugs raise serum uric acid level by an increase in uric acid production or a decrease in uric acid excretion, while others lower serum uric acid level by a decrease in uric acid production or an increase in uric acid excretion. In addition, some drugs show so-called biphasic effect; ie, hyperuricemic in lower doses but hypouricemic in higher doses. Hyperuricemic agents contribute to gout and/or urate nephropathy. Among them, pyrazinamide is often used to determine the defective site(s) of uric acid transport in renal tubules in conjunction with uricosuric agents, such as benzbromarone or probenecid. In contrast, the clinical significance of hypouricemic agents other than uricosuric agents has not been emphasized. However, some may induce acute uric acid nephropathy by a significant increase in uric acid excretion. In this review, drugs affecting uric acid metabolism are summarized with regard to their mechanism of action and clinical significance.

Topics: Allopurinol; Diuretics; Fructose; Gout; Gout Suppressants; Humans; Inosine; Kidney Diseases; Niacin; Purines; Uric Acid; Xylitol

Topics: Aged; Allopurinol; Colchicine; Female; Gout; Humans; Indomethacin; Male; Middle Aged; Myelography; Spinal Stenosis; Tomography, X-Ray Computed

Gout is a syndrome caused by an inflammatory response to the formation of monosodium urate monohydrate crystals which develop secondary to hyperuricaemia. Acute and chronic forms occur. Hyperuricaemia may be due to environmental and/or genetic factors. It most commonly affects middle-aged males. This article discusses the management of both acute and chronic gout.

Topics: Acute Disease; Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Female; Gout; Humans; Male; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Animals; Antioxidants; Gout; Humans

A critical appraisal of the evidence commonly cited to support a link between high urate excretion and calcium oxalate (CaOx) urinary calculi is presented. Two theories have been invoked to provide a scientific explanation for urate's apparent promotory effect. The first proposes that urinary urate crystals promote CaOx precipitation by the phenomenon of epitaxy; the second hypothesis is that colloidal particles of urate reduce the inhibitory activity of urinary glycosaminoglycans (GAGs) which normally prevent the crystallization of CaOx. However, to the present, neither has been verified experimentally. More recent research from our group has revealed that at normal physiological pH values dissolved urate directly promotes CaOx precipitation by the classic 'salting-out' effect by enhancing nucleation, growth and aggregation of CaOx crystals. It is therefore suggested that the beneficial effect of allopurinol in reducing CaOx stone recurrences may be attributed to its lowering the urinary output of urate and thereby reducing the probability that CaOx will be salted out of urine, rather than to epitaxy or inactivation of urinary GAGs.

Topics: Allopurinol; Calcium Oxalate; Glycosaminoglycans; Gout; Humans; Hydrogen-Ion Concentration; Hyperoxaluria; Kidney Calculi; Uric Acid; Urinary Calculi

Nonsteroidal anti-inflammatory drugs (NSAIDs) are now commonly used for the treatment of acute gout, but caution is required in view of their adverse effects, especially in the elderly. Colchicine is still an effective acute agent, but care must be taken to monitor toxicity. Intra-articular glucocorticosteroid therapy is useful and very safe; oral steroids and corticotrophin (adrenocorticotrophic hormone) may have a small role in acute therapy and seem safe when used over short time spans. Low dose colchicine may have a cost and toxicity advantage over NSAIDs in the prophylaxis of gout when commencing therapy aimed at reducing elevated plasma urate concentrations. Allopurinol is more frequently used than uricosuric agents such as probenecid, and toxicity may be largely avoided by tailoring dosage schedules according to renal function.

Topics: Adrenocorticotropic Hormone; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Double-Blind Method; Glucocorticoids; Gout; Gout Suppressants; Humans; Probenecid; Sulfinpyrazone

Topics: Allopurinol; Female; Gout; Humans; Kidney Diseases; Kidney Transplantation; Male

Topics: Allopurinol; Gout; Humans; Uric Acid

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Colchicine; Diet; Gout; Humans; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Gout; Humans; Kidney; Kidney Failure, Chronic; Uric Acid

Topics: Allopurinol; Gout; Humans; Xanthine Oxidase

Gout is a clinical syndrome encompassing a group of metabolic diseases that are all characterized by abnormal uric acid metabolism. In its fullest form, gout is defined by: an increase in the serum urate concentration; characteristic, recurrent, acute arthritic attacks, with monosodium urate monohydrate crystals demonstrable in synovial fluid leukocytes; tophi, usually in and around joints of the extremities, composed of monosodium urate monohydrate deposits; renal disease, often accompanied by hypertension with glomerular, tubular, interstitial, and vascular involvement; and uric acid nephrolithiasis. Any combination of these manifestations may occur, although tophi and urate nephropathy rarely antedate gouty arthritis.

Topics: Acute Disease; Adult; Allopurinol; Anti-Inflammatory Agents; Arthritis; Arthrography; Calcinosis; Chronic Disease; Colchicine; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Middle Aged; Probenecid; Uric Acid

Topics: Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Indomethacin; Probenecid; Sulfinpyrazone

There has been an explosion of knowledge in disorders of purine and pyrimidine metabolism during the last 20 years. During this time, more than 10 diseases have been discovered and their metabolic bases studied. Hyperuricemia and gout remain the most common clinical disorder. Rarely these disorders are explainable by an inherited enzyme abnormally, such as hypoxanthine-guanine phosphoribosyltransferase deficiency, phosphoribosyl-pyrophosphate synthetase deficiency, or glucose-6-phosphatase deficiency. The description of immunodeficiency syndromes in association with purine enzyme deficiency has led to a novel area of investigation encompassing the biochemical basis for immune function. Although less information is available concerning the other diseases associated with renal calculi, myopathy, anemia, and central nervous system dysfunction, further research will elucidate important metabolic relationships. These will no doubt expand our understanding of the pathogenesis of these disorders and provide innovative therapeutic approaches.

Topics: 5'-Nucleotidase; Adenine Phosphoribosyltransferase; Adenosine Deaminase; AMP Deaminase; Gout; Guanine Deaminase; Humans; Hypoxanthine Phosphoribosyltransferase; Immunologic Deficiency Syndromes; Nucleotidases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Xanthine Oxidase

Rheumatic diseases are prevalent in the elderly population, resulting in high morbidity caused mainly by lack of mobility. Consequently, the use of antirheumatic drugs in older persons is extensive. This review outlines some of the hazards encountered in the use of antirheumatic drugs in the elderly. Analgesics such as propoxyphene and acetaminophen are useful adjuncts to the treatment of arthritic pain, but propoxyphene has been associated with respiratory depression, and renal clearance of acetaminophen is reduced in elderly subjects. Salicylates may cause deafness, and like the other nonsteroidal anti-inflammatory drugs, may cause salt and water retention resulting in congestive cardiac failure. Phenylbutazone should not be used because of the risk of blood dyscrasia, and indomethacin has been reported as interfering with the antihypertensive effect of beta-blockers. Chloroquine levels may be raised in patients with impaired renal function, and there is increased risk of retinal damage with the drug in elderly subjects. Injectable gold compounds and penicillamine are not contraindicated in the elderly, because they are just as efficacious as in younger persons for the treatment of rheumatoid arthritis. Toxicity due to gold compound is not increased in the elderly, but skin rashes and abnormalities of taste do occur more commonly in elderly patients treated with penicillamine. Corticosteroids do not affect disease progression and therefore should be used only in acute severe disease for short periods of time. As in the younger population, treatment of gout in the elderly is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex Hormones; Age Factors; Aged; Allopurinol; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Rheumatoid; Chloroquine; Female; Gold; Gout; Humans; Male; Methotrexate; Middle Aged; Osteoarthritis; Penicillamine; Probenecid

Topics: Allopurinol; Arthritis; Aspirin; Blood Urea Nitrogen; Glomerular Filtration Rate; Gout; Humans; Kidney Diseases; Uric Acid

Topics: Acute Kidney Injury; Allopurinol; Diuretics; Gout; Humans; Kidney Calculi; Uric Acid

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Benzbromarone; Colchicine; Gout; Gout Suppressants; Humans; Indomethacin; Kidney; Phenylbutazone; Probenecid; Sulfinpyrazone; Uric Acid

Although chronic tophaceous gout has become increasingly uncommon, hyperuricemia and acute gout are still common clinical entities. Most patients with hyperuricemia are under-excreters, and many of these cases are drug induced. Since longstanding asymptomatic hyperuricemia does not appear to cause progressive renal insufficiency, and uric acid renal stones are uncommon in underexcreters, these patients generally require no treatment. The minority of patients who overproduce uric acid are at increased risk for urolithiasis, and therapy should be decided on an individual basis. Acute gout is best treated with colchicine or indomethacin. The newer non-steroidal anti-inflammatory drugs (ie, ibuprofen, sulindac) may prove to be equally effective and are associated with fewer gastrointestinal side effects. Prophylaxis should be undertaken in patients with recurrent gout or documented uric acid urolithiasis. Although uricosuric drugs appear to be less toxic than allopurinol, they should not be used in patients who overproduce uric acid or in patients who have a history of urolithiasis or renal insufficiency. The allopurinol hypersensitivity syndrome is being reported with increased frequency and may be fatal.

Topics: Allopurinol; Arthritis; Aspirin; Colchicine; Diuretics; Gout; Gout Suppressants; Humans; Indomethacin; Phenylbutazone; Uric Acid

Topics: Allopurinol; Gout; Humans; Kidney Calculi; Kidney Diseases; Nephritis, Interstitial; Purines; Uric Acid

Topics: Allopurinol; Female; Gout; Humans; Long-Term Care; Male; Risk; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Female; Gout; Humans; Kidney Calculi; Male; Nephritis, Interstitial; Purines; Uric Acid

Topics: Acute Disease; Allopurinol; Arthritis; Aspirin; Colchicine; Coronary Disease; Diuretics; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Indomethacin; Kidney; Kidney Calculi; Kidney Diseases; Lead Poisoning; Lymphoproliferative Disorders; Myeloproliferative Disorders; Phenylbutazone; Platelet Aggregation; Probenecid; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Ribose-Phosphate Pyrophosphokinase; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Colchicine; Female; Gout; Humans; Kidney Calculi; Male; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Biological Transport; Diuretics; Glomerular Filtration Rate; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney Diseases; Kidney Tubules; Lactates; Lesch-Nyhan Syndrome; Nucleosides; Nucleotides; Purines; Risk; Sodium; Uric Acid

Topics: Allopurinol; Balneology; Benzofurans; Crystallization; Diagnosis, Differential; Exercise Therapy; Glomerular Filtration Rate; Gout; Probenecid; Sulfinpyrazone; Uric Acid; Urinary Calculi

Topics: Allopurinol; Arthritis; Chronic Disease; Colchicine; Gout; Humans; Indomethacin; Naproxen; Phenylbutazone; Probenecid; Sulfinpyrazone; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Gold; Gout; Humans; Lupus Erythematosus, Systemic; Osteoarthritis; Penicillamine; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing; Vasculitis

The spectrum of kidney and urinary tract disorders related to purines comprises acute hyperuricosuric nephropathy, chronic urate nephropathy and urolithiasis. Two factors in the development of acute hyperuricosuric nephropathy are increased uric acid concentration and low pH in the tubular fluid. Chronic urate nephropathy still possess several problems: incidence (although this seems to be decreasing, presumably owing to effective prevention), the source of interstitial urate, the cause of the interstitial deposition of urate, and the role of urate deposits in the pathogenesis of the interstitial nephropathy. The relation of the experimental nephropathy to the pathogenesis of chronic urate nephropathy in the human is not yet clear but a model is proposed according to which interstitial urate derives from two sources: hyperuricaemic plasma and hyperuricosuric tubular fluid. Urolithiasis related to purines leads to uric acid-urate stones, xanthine stones, 2,8-dihydroxyadenine stones, iatrogenic xanthine and oxipurinol stones, and possibly calcium stones. Pathogenetic factors in uric acid lithiasis are hyperuricosuria (whether due to an inborn enzyme abnormality or of unknown aetiology) and low urinary pH; oliguria is a contributory factor. There remain several open questions about uric acid lithiasis: incidence, the shift of its location from lower to upper urinary tract, the interplay of pathogenetic factors, and the role of compounds which inhibit crystallization.

Topics: Adenine Phosphoribosyltransferase; Allopurinol; Animals; Calcium; Gout; Humans; Hydrogen-Ion Concentration; Hypoxanthine Phosphoribosyltransferase; Kidney Calculi; Kidney Diseases; Kidney Failure, Chronic; Oxypurinol; Purines; Sodium; Solubility; Uric Acid; Urologic Diseases; Xanthine Oxidase; Xanthines

Topics: Amidophosphoribosyltransferase; Animals; Female; Glucosephosphate Dehydrogenase Deficiency; Glutamine; Gout; Humans; Inosine Monophosphate; Kinetics; Liver; Molecular Weight; Nucleotidases; Pentosyltransferases; Phosphoribosyl Pyrophosphate; Phosphotransferases; Placenta; Pregnancy; Purine Nucleotides; Ribose-Phosphate Pyrophosphokinase; Ribosemonophosphates; Xanthine Oxidase

Topics: Adult; Allopurinol; Colchicine; Diagnosis, Differential; Female; Gout; Humans; Indomethacin; Male; Middle Aged; Phenylbutazone; Prognosis; Uric Acid; Uricosuric Agents

Benzbromarone1 is a benzofuran derivative which lowers serum urate and increases urinary urate excretion in normal, hyperuricaemic and gouty subjects. In open short- and long-term studies benzbromarone reduced serum uric acid levels by one-third to one-half and maintained its effectiveness for periods of up to 8 years. Single-dose experimental studies have shown benzbromarone to have a urate-lowering effect similar to that of a therapeutic dose of probenecid or sulphinpyrazone, but unlike these drugs benzbromarone can be administered in a once daily regimen. In 2 short-term comparative therapeutic trials in a small number of patients with hyperuricaemia, 80mg of micronised benzbromarone daily was at least as effective as 1000mg of probenecid or 300mg of allopurinol daily in lowering serum uric acid levels. Side-effects during benzbromarone administration are usually mild and primarily gastrointestinal in nature.

Topics: Aspirin; Benzbromarone; Benzofurans; Drug Interactions; Fasting; Gout; Humans; Kidney Diseases; Kinetics; Lipid Metabolism; Pyrazinamide; Triglycerides; Uric Acid; Xanthine Oxidase

Topics: Acute Disease; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Gout; Humans; Long-Term Care; Uric Acid

Topics: Adult; Alcoholism; Cholesterol, Dietary; Chylomicrons; Diet, Reducing; Dietary Fats; Female; Gout; Humans; Hyperlipidemias; Purine-Pyrimidine Metabolism, Inborn Errors; Triglycerides; Uricosuric Agents; Xanthine Oxidase

A reduction in the serum urate concentration in hyperuricemic subjects can be achieved by increasing the renal excretion of uric acid, by inhibiting its synthesis, or by a combination of both modalities. The three most commonly used hypouricemic drugs are probenecid, sulfinpyrazone and allopurinol. Each drug has been considered in detail with regard to its mechanism of action, metabolism, diverse metabolic effects, side effects and interaction with other drugs. In addition, guidelines for the use of these drugs in hyperuricemic subjects are proposed.

Topics: Allopurinol; Diuresis; Gout; Homeostasis; Humans; Kidney Tubules; Probenecid; Sulfinpyrazone; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Bloodletting; Chlorambucil; Erythropoiesis; Gout; Humans; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera; Uric Acid

Topics: Adenine; Allopurinol; Carbon Radioisotopes; Erythrocytes; Fibroblasts; Glucosephosphate Dehydrogenase; Glutamine; Glutathione Reductase; Gout; Guanine; Humans; Hypoxanthines; Lesch-Nyhan Syndrome; Liver; Metabolic Diseases; Molecular Weight; Orotic Acid; Pentosyltransferases; Purines; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Colchicine; Gout; Humans; Indomethacin; Kidney Calculi; Probenecid; Sulfinpyrazone; Uric Acid; Uricosuric Agents

Topics: Adenine Nucleotides; Anemia, Hemolytic, Congenital Nonspherocytic; Glutamate Dehydrogenase; Glutaminase; Glutathione Reductase; Glycogen Storage Disease; Gout; Guanine Nucleotides; Humans; Hypoxanthines; Immunologic Deficiency Syndromes; Kinetics; Lesch-Nyhan Syndrome; Molecular Weight; Mutation; Pentosephosphates; Pentosyltransferases; Purine-Pyrimidine Metabolism, Inborn Errors; Ribose; Species Specificity; Xanthine Oxidase; Xanthines

Topics: Amidophosphoribosyltransferase; Chemical Phenomena; Chemistry; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Gout; Humans; Inosine Monophosphate; Lesch-Nyhan Syndrome; Phosphoribosyl Pyrophosphate; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Xanthine Oxidase; Xanthines; Xeroderma Pigmentosum

Topics: Allopurinol; Chemical Phenomena; Chemistry; Depression, Chemical; Feedback; Gout; Humans; Kidney; Purines; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Creatinine; Diet Therapy; Erythrocytes; Gout; Humans; Hypoxanthines; Lesch-Nyhan Syndrome; Metabolism, Inborn Errors; Myeloproliferative Disorders; Pentosyltransferases; Prenatal Diagnosis; Protein Binding; Purines; Uric Acid

Topics: Absorption; Allopurinol; Aspirin; Benzothiadiazines; Diuretics; Ethanol; Gout; Humans; Kidney Calculi; Kidney Tubules; Sodium Chloride Symporter Inhibitors; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Gout; Humans; Kidney; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Uric Acid; Uricosuric Agents

Topics: Adenine; Adrenocorticotropic Hormone; Allopurinol; Animals; Glycogen; Gout; Humans; Lesch-Nyhan Syndrome; Methylene Blue; Orotic Acid; Pentosephosphates; Phosphoric Acids; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribose; Thiadiazoles; Thyrotropin; Transferases; Urate Oxidase; Uric Acid

Topics: Adrenocorticotropic Hormone; Allopurinol; Analgesics; Arthritis, Juvenile; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Gold; Gout; Humans; Phenylbutazone; Probenecid; Prognosis; Rheumatic Diseases; Rheumatic Fever

Topics: Allopurinol; Chemical Phenomena; Chemistry; Colchicine; Gout; Humans; Phagocytosis; Probenecid; Purines; Uric Acid

Topics: Adrenal Cortex Hormones; Allopurinol; Colchicine; Gout; Humans; Indomethacin; Phenylbutazone; Probenecid; Sulfinpyrazone; Uric Acid; Uricosuric Agents; Xanthine Oxidase; Xanthines

Topics: Acute Disease; Allopurinol; Chronic Disease; Colchicine; Gout; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Kidney Tubules; Probenecid; Purines; Sulfinpyrazone; Uric Acid; Uricosuric Agents

Topics: Adult; Allopurinol; Child; Drug Hypersensitivity; Drug Interactions; Gout; Humans; Iron; Kidney Diseases; Nucleic Acids; Purines; Pyrimidines; Tryptophan; Uric Acid; Urinary Calculi; Xanthines

Topics: Acute Disease; Allopurinol; Arthritis; Colchicine; Gout; Humans; Orotic Acid; Probenecid; Structure-Activity Relationship; Sulfinpyrazone; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Colchicine; Glycogen Storage Disease Type I; Gout; Humans; Lesch-Nyhan Syndrome; Metabolism, Inborn Errors; Pentosyltransferases; Purine Nucleotides; Purines; Uric Acid

Topics: Allopurinol; Chondrocalcinosis; Colchicine; Diagnosis, Differential; Diet Therapy; Gout; Humans; Inosine Nucleotides; Joint Diseases; Metabolic Diseases; Orotic Acid; Purines; Urate Oxidase; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Gout; Humans; Uric Acid

Topics: Adenine; Adolescent; Adult; Allopurinol; Azathioprine; Child; Child, Preschool; Female; Gout; Humans; Hypoxanthines; Male; Middle Aged; Pedigree; Pharmacogenetics; Phenotype; Purines; Transferases; Uric Acid

Topics: Acute Disease; Adrenal Cortex Hormones; Arthritis; Chronic Disease; Colchicine; Glomerular Filtration Rate; Gout; Phenylbutazone; Purines; Urate Oxidase; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Acute Disease; Allopurinol; Antineoplastic Agents; Benzofurans; Colchicine; Female; Gout; Humans; Phenylbutazone; Pregnancy; Probenecid; Sulfinpyrazone; Uricosuric Agents; Vasodilator Agents; Zoxazolamine

Topics: Allopurinol; Chemical Phenomena; Chemistry; Gout; Humans; Purines; Uric Acid; Xanthines

Topics: Alkylating Agents; Allopurinol; Analgesics; Anti-Inflammatory Agents; Antimalarials; Antimetabolites; Arthritis, Rheumatoid; Arthroplasty; Aspirin; Gold; Gout; Humans; Immunosuppressive Agents; Indomethacin; Phenacetin; Polymyalgia Rheumatica; Prednisolone; Prednisone; Rheumatic Fever; Synovitis

Topics: Adult; Allopurinol; Diet Therapy; Female; Gout; Humans; Male; Middle Aged; Probenecid; Sulfinpyrazone

Topics: Allopurinol; Chemical Phenomena; Chemistry; Gout; Humans

Topics: Enzyme Therapy; Gout; Humans; Xanthine Oxidase

Topics: Allopurinol; Arthritis; Carbon Isotopes; Colchicine; Glutamine; Gout; Humans; Kidney; Orotic Acid; Purines; Uric Acid

Topics: Drug Interactions; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid; Xanthine Oxidase

The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients.. This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses.. This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33).. Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

Topics: Aged; Allopurinol; Frail Elderly; Frailty; Gout; Humans; Risk Factors

To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the 'start-low go-slow' dose approach.. A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months.. Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo.. Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the 'start-low go-slow' strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period.. ACTRN 12618001179224.

Topics: Adult; Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Symptom Flare Up; Treatment Outcome; Uric Acid

We previously reported on the FREED study, which found that febuxostat reduced the risk of adverse clinical outcome in patients with asymptomatic hyperuricemia without gout. We have now investigated outcomes in subgroups of FREED patients with and without a history of cardiovascular disease (CVD).. We performed a post hoc subgroup analysis of 1070 patients randomized to the febuxostat or non-febuxostat group and followed for 36 months.. At baseline, 234 patients (21.9%) had a history of CVD, including 86 patients with stroke (36.8%), 90 with coronary artery disease (38.5%), 74 with heart failure (31.6%), and 25 with vascular disease (10.7%). The risk for the primary composite endpoint, i.e., cerebral, cardiovascular, and renal events and all deaths, was higher in patients with CVD than in those without CVD (34.2% vs 23.7%; p < 0.001). Treatment with febuxostat lowered rates of the primary composite endpoint in patients with CVD (hazard ratio [HR] 0.601, 95% CI 0.384 to 0.940, p = 0.026), and these effects were consistently observed in subgroups with and without CVD (p = 0.227 for treatment by subgroup interaction). Furthermore, in the subgroup with CVD, all-cause mortality was significantly lower in the febuxostat group than in the non-febuxostat group (HR 0.160, 95% CI 0.047 to 0.547, p = 0.004), with a significant subgroup interaction (p = 0.007 for treatment by subgroup interaction).. In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of the composite of cerebral, cardiovascular, and renal events and death in the secondary prevention setting.

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome

To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout.. We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points.. Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups.. Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Quality of Life; Treatment Outcome; Uric Acid

To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial.. Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause.. Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%.. In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Thiazoles; Treatment Outcome; Uric Acid

To determine the long-term use of and adherence to urate-lowering therapy (ULT), serum urate (SU) control, and self-reported flares in participants from a randomized controlled trial of allopurinol dose escalation, in order to achieve target SU concentration (< 0.36 mmol/L) in people with gout.. For surviving study participants, ULT dispensing and SU testing within the preceding 12 months was obtained by medical record review. A phone interview was conducted to determine self-reported flares and adherence.. Over a mean follow-up of 6.5 (SD 2.5) years since enrollment, 60 out of 183 (33%) participants had died. Review of the 119 surviving participants showed that 98 (82%) were receiving allopurinol, 5 (4%) were receiving febuxostat, and 10 (8%) were not receiving ULT; for the remaining 6 (5.0%), ULT use could not be determined. In those receiving allopurinol, the mean dose was 28.1 (range -600 to 500) mg/day lower than at the last study visit; 49% were receiving the same dose, 18% were on a higher dose, and 33% were on a lower dose than at the last study visit. SU values were available for 86 of the 119 (72%) participants; 50 out of 86 (58%) participants had an SU concentration of < 0.36 mmol/L. Of the 89 participants who participated in the phone interview, 19 (21%) reported a gout flare in the preceding 12 months and 79 (89%) were receiving allopurinol; 71 (90%) of those receiving allopurinol reported 90% or greater adherence.. Most of the surviving participants in the allopurinol dose escalation study had good real-world persistence with allopurinol, remained at target SU, and had a low number of self-reported flares.

Topics: Allopurinol; Follow-Up Studies; Gout; Gout Suppressants; Humans; Symptom Flare Up; Treatment Outcome; Uric Acid

The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion; however, the standard urate-lowering therapy (ULT) recommendation is first-line xanthine oxidase inhibitor (XOI), irrespective of the cause of hyperuricemia. This comparative effectiveness clinical trial was undertaken to compare first-line nontitrated low-dose benzbromarone (LDBen) uricosuric therapy to XOI ULT with low-dose febuxostat (LDFeb) in gout patients with renal uric acid underexcretion.. More participants in the LDBen group achieved the serum urate target than those in the LDFeb group (61% compared to 32%, P < 0.001). Rates of adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of greater transaminase elevation in the LDFeb group (4% for LDBen compared to 15% for LDFeb, P = 0.008).. Compared to LDFeb, LDBen has superior urate-lowering efficacy and similar safety in treating relatively young and healthy patients with renal uric acid underexcretion-type gout.

Topics: Allopurinol; Benzbromarone; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Prospective Studies; Treatment Outcome; Uric Acid

Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.. ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.. Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77).. In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.. UK National Institute for Health and Care Research.

Topics: Aged; Allopurinol; Coronary Artery Disease; Female; Gout; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Stroke; Treatment Outcome; United Kingdom; Uric Acid

The present study compared the efficacy and safety of low-dose febuxostat versus allopurinol in chronic kidney disease (CKD) patients complicated with hyperuricemia (HUA).. In this double-centre, randomized, controlled study, 120 CKD patients complicated with HUA were recruited and randomly assigned to low-dose febuxostat group (20 mg/day) or allopurinol group (200 mg/day) at 1:1 ratio. The serum creatinine (Scr), serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were measured at baseline (M0), month (M) 1, M3, and M6. Besides, the drug-related adverse events (AEs) were recorded. The primary outcome was the proportion of patients showing a > 10% decline in eGFR from M0 to M6.. The eGFR level was increased at M6, but similar at M0, M1 and M3 in febuxostat group compared with allopurinol group. Notably, the proportion of patients with >10% decline in eGFR from M0 to M6 was decreased in febuxostat group compared with allopurinol group. However, there was no difference of Scr, SUA at M0, M1, M3 and M6 between febuxostat group and allopurinol group. Moreover, there was no difference of drug-related AEs between febuxostat group and allopurinol group. Further subgroup analysis exhibited that low-dose febuxostat presented superior effect on attenuating eGFR decline and lowering SUA level compared with allopurinol in CKD stage 3 subgroup, but not in CKD stage 2 subgroup.. Low-dose febuxostat may exhibit a superior renal-protective effect, non-inferior SUA lowering ability and safety profile compared with allopurinol in CKD patients complicated with HUA.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid

Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.. A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.. In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Topics: Adult; Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Pulse Wave Analysis; Risk Factors; Thiazoles; Treatment Outcome; Uric Acid

Currently available guidelines on urate-lowering therapy (ULT) initiation in acute gout flare are conflicting. We compared the time to complete resolution of acute gout flare between early and late allopurinol initiation.. This 28-day, randomized controlled, open-label trial included patients with crystal-proven gout who were presented with acute gout flare within 72 h of arthritis onset. Exclusion criteria were advanced renal failure, ongoing ULT, and presence of the HLA-B*5801 allele. Allopurinol was used on days 1 and 14 in early and late groups, respectively. Primary outcome was time to complete arthritis resolution, and secondary outcomes were time to clinical resolution; arthritis relapse; laboratory parameters; and adverse events.. One hundred seventeen patients were randomized to early and late allopurinol groups (n = 59 and 58, respectively). One patient in each group was lost to follow-up; therefore, 115 patients were included in the modified intention-to-treat analysis. Baseline characteristics were comparable between the groups. The median time to complete resolution was not significantly different between the early and late allopurinol groups (6 [5-14] and 6 [5-7] days, respectively; p = 0.14). The median time to clinical resolution was 4 [3-6] days in both groups (p = 0.12). Other secondary outcomes were not significantly different. Serious adverse events did not occur in either group.. Early allopurinol initiation during an acute gout flare did not lead to significant changes in time to resolution, flare recurrence, and inflammatory markers. Key Points • Allopurinol Initiation in Gout.

Topics: Allopurinol; Double-Blind Method; Gout; Gout Suppressants; Humans; Symptom Flare Up; Time-to-Treatment; Treatment Outcome; Uric Acid

To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect.. We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed.. Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events.. Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

Topics: Adolescent; Adult; Allopurinol; Blood Pressure; C-Reactive Protein; Cross-Over Studies; Dilatation, Pathologic; Double-Blind Method; Endothelium, Vascular; Female; Gout; Humans; Hypertension; Male; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid; Uricosuric Agents; Young Adult

To explore patient satisfaction, gout knowledge, medication adherence and flares among participants receiving nurse-led or general practitioner (GP)-led care of gout in the Nottingham Gout Treatment Trial phase-II (NGTT-II).. A total of 438 participants of NGTT-II were sent a questionnaire enquiring about gout knowledge, satisfaction with health-care practitioner, urate-lowering treatment being undertaken, and gout flares ⩾1 year after their final visit. Nurse-led care participants were asked about their preference for receiving gout treatment from either a GP or a nurse.. Completed questionnaires were returned by 82% of participants. Participants previously receiving nurse-led care reported greater satisfaction with health-care practitioner (P < 0.001), had better gout knowledge (P = 0.02), were more likely to be taking urate-lowering treatment [adjusted relative risk (95% CI) 1.19 (1.09, 1.30)], and self-reported fewer flares in the previous 12 months [median (inter-quartile range) 0 (0-0) vs 1 (0-3), P < 0.001] than those receiving GP-led care. Of participants receiving nurse-led care, 41-63% indicated preference for receiving gout treatment from a nurse, while only 5-20% indicated preference for receiving treatment from GPs.. The results of this study favour nurse-led care, involving individualized patient education and engagement and a treat-to-target strategy, in terms of patient acceptability, long-term adherence, and flares. Further research is required to evaluate the feasibility of implementing such a model of care in clinical practice.

Topics: Allopurinol; Follow-Up Studies; General Practitioners; Gout; Gout Suppressants; Health Care Surveys; Humans; Medication Adherence; Nurses; Patient Satisfaction

The aims of this study were to determine factors that predict serum urate (SU) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24-month open, randomized, controlled, parallel-group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and SU was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (ROC) curves were used to identify a minimum oxypurinol concentration predictive of SU < 6 mg/dL. There was a wide range of SU concentrations for each allopurinol dose. The relationship between sensitivity to allopurinol and allopurinol metabolism for each 100 mg allopurinol dose increase varied between individuals. Body mass index (P = 0.023), creatinine clearance (CrCL; P = 0.037), ABCG2 Q141K (P = 0.019), and SU (P = 0.004) were associated with sensitivity to allopurinol. The minimum oxypurinol concentration for achieving the urate target was found to be about 104 μmol/L, but predictive accuracy was poor (ROC curve area under the curve (AUC) 0.65). The minimum therapeutic oxypurinol concentration was found to increase with decreasing renal function. Although there is a positive relationship between change in oxypurinol and change in SU concentration, a minimum therapeutic oxypurinol is dependent on CrCL and cannot reliably predict SU target. Other variables, including ABCG2 Q141K genotype, impact on sensitivity to allopurinol (ACTRN12611000845932).

Topics: Aged; Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Body Mass Index; Creatinine; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Neoplasm Proteins; Oxypurinol; Renal Elimination; ROC Curve; Treatment Outcome; Uric Acid

A direct comparison of the effects of febuxostat and allopurinol on flow-mediated dilatation (FMD) will help to clarify which agent provides a better reduction of cardiovascular risk in hypertensive patients. Hypertensive patients with hyperuricemia were randomized into a febuxostat (10-40 mg, n = 33) or allopurinol (100-200 mg, n = 31) group and followed up for 6 months. Both the febuxostat (7.9 ± 1.3 mg/dL vs 5.6 ± 1.0 mg/dL, P < .001) and allopurinol (8.2 ± 1.3 mg/dL vs 6.1 ± 1.0 mg/dL, P < .001) groups exhibited significant reductions in uric acid after treatment. There was no significant difference in the change in FMD between the two treatment groups (0.6 ± 2.6% vs 0.2 ± 2.3%, P = .504). However, stratified analysis showed that febuxostat achieved a significantly greater change in FMD compared to allopurinol in the elderly group (1.3 ± 2.9% vs -0.7%±1.8%, P = .047). There was no difference in the improvement of FMD between febuxostat and allopurinol, but febuxostat may provide an improvement of FMD in elderly people.

Topics: Aged; Allopurinol; Dilatation; Febuxostat; Gout; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Treatment Outcome; Xanthine Oxidase

Cherry concentrate has been suggested to reduce serum urate (SU) and gout flares. The aims of this study were to determine the magnitude of the effect of tart cherry concentrate on SU in people with gout, the most effective dose of tart cherry concentrate for lowering SU, and adverse effects.. Fifty people with gout and SU > 0.36 mmol/l were recruited. Half were on allopurinol and half were on no urate-lowering therapy. Participants were randomized to receive tart cherry juice concentrate: placebo, 7.5 ml, 15 ml, 22.5 ml or 30 ml twice daily for 28 days. Blood samples were taken at baseline, then at 1, 3 and 5 h post cherry and then on days 1, 3, 7, 14, 21 and 28. The area under the curve for SU was calculated over the 28-day study period.. Cherry concentrate dose had no significant effect on reduction in SU area under the curve, urine urate excretion, change in urinary anthocyanin between day 0 and day 28, or frequency of gout flares over the 28-day study period (P = 0.76). There were 24 reported adverse events, with only one (hyperglycaemia) considered possibly to be related to cherry concentrate. Allopurinol use did not modify the effect of cherry on SU or urine urate excretion.. Tart cherry concentrate had no effect on SU or urine urate excretion. If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in SU.. Australian New Zealand Clinical Trials Registry (ANZCTR), https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368887, ANZCTR 12615000741583).

Topics: Adult; Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Phytotherapy; Plant Extracts; Prunus avium; Treatment Outcome; Uric Acid

Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.. We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (<6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed.. From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years [SD 6·4], 5225 [85·3%] men, 903 [14·7%] women, 2046 [33·4%] with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029-2052) and median on-treatment follow-up was 1324 days (IQR 870-1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients [1·72 events per 100 patient-years]) was non-inferior to allopurinol (241 patients [2·05 events per 100 patient-years]; adjusted HR 0·85 [95% CI 0·70-1·03], p<0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 [0·6%] patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five [0·2%] patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group.. Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol.. Menarini, Ipsen, and Teijin Pharma Ltd.

Topics: Aged; Allopurinol; Cardiovascular Diseases; Denmark; Febuxostat; Female; Gout; Gout Suppressants; Hospitalization; Humans; Male; Prospective Studies; Sweden; Treatment Outcome; United Kingdom; Uric Acid

To explore patient perception of the role of a nurse-led complex package of care in facilitating engagement with urate-lowering therapies (ULTs) in the management of gout.. Thirty people who had participated in a randomised controlled trial investigating the effect of a nurse-led complex package of care for gout, were purposively sampled and interviewed between 18-26 months after the end of the trial. Interviews were recorded, transcribed and analysed using a modified grounded-theory approach. Data were managed using Nvivo. STATA v15 was used to describe summary statistics.. Participants described their views and experiences of engaging with a nurse-led intervention designed to provide holistic assessment, individualised patient education, and involvement in shared decision-making for the long-term management of gout. The analysis revealed key themes in how nurse-led intervention facilitated engagement with ULT, namely by proving improved knowledge and understanding of gout and its treatment, involvement of patients in decision-making about treatment, and increased confidence about benefits from treatment. However, some treatment uncertainty and concern remained and one participant free of gout flares discontinued ULT, while another halved the dose after the end of the trial.. This study reports data on patient experience of engaging with ULT to manage gout after receiving nurse-led care. It demonstrates that shared decision-making and the joint efforts of fully informed practitioners and patients persuades patients to engage with ULTs, and that experiencing the benefits of curative treatment motivates them to maintain adherence.

Topics: Allopurinol; Clinical Competence; Decision Making, Shared; Female; France; Gout; Gout Suppressants; Humans; Interviews as Topic; Male; Medication Adherence; Nurse-Patient Relations; Patient Satisfaction; Practice Patterns, Nurses'; Qualitative Research; Risk Assessment; Severity of Illness Index; Treatment Outcome; Uric Acid

The purpose of this study was to test a pharmacist-led intervention to improve gout treatment adherence and outcomes.. We conducted a site-randomized trial (n=1463 patients) comparing a 1-year, pharmacist-led intervention to usual care in patients with gout initiating allopurinol. The intervention was delivered primarily through automated telephone technology. Co-primary outcomes were the proportion of patients adherent (proportion of days covered ≥0.8) and achieving a serum urate <6.0 mg/dl at 1 year. Outcomes were reassessed at year 2.. Patients who underwent intervention were more likely than patients of usual care to be adherent (50% vs 37%; odds ratio [OR] 1.68; 95% confidence interval [CI] 1.30, 2.17) and reach serum urate goal (30% vs 15%; OR 2.37; 95% CI 1.83, 3.05). In the second year (1 year after the intervention ended), differences were attenuated, remaining significant for urate goal but not for adherence. The intervention was associated with a 6%-16% lower gout flare rate during year 2, but the differences did not reach statistical significance.. A pharmacist-led intervention incorporating automated telephone technology improved adherence and serum urate goal in patients with gout initiating allopurinol. Although this light-touch, low-tech intervention was efficacious, additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes.

Topics: Adult; Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Odds Ratio; Patient Participation; Pharmacists; Professional Role; Telephone; Treatment Outcome; Uric Acid

Recruitment to clinical trials can be challenging. Methods that improve the efficiency of trial recruitment are needed to increase successful study completions. The aim of this study was to ascertain whether sending an audio-visual presentation on a digital versatile disc (DVD), along with usual study invitation materials, would improve recruitment to the Febuxostat versus Allopurinol Streamlined Trial (FAST), a clinical trial in patients with established gout.. Potential participants for the FAST study who were identified by searches of GP records in Scottish primary care practices between August 2013 and July 2014 were included in this study. Individuals were randomly allocated to receive either a standard invitation (letter and information leaflet) or a standard invitation and a DVD containing an audio-visual presentation explaining the background and operation of FAST. Data on invitation response rates, screening attendances and randomisations were collected by research nurses.. One thousand fifty potential participants were invited to take part in FAST during this period. 509 individuals were randomised to receive the DVD presentation and the standard invitation and 541 received a standard invitation only. DVD recipients were less likely to respond to the initial invitation (adjusted OR 0.76, CI 0.58-0.99) and marginally less likely to return a positive response (OR 0.75, CI 0.59-0.96). There was no statistically significant difference between the groups in attendance for screening or randomisation. The DVD did not influence the age, gender, or socioeconomic deprivation scores of those responding positively to a letter of invitation.. The inclusion of a DVD presentation with FAST study invitations did not make any practical difference to the rate of positive response to invitation. Further innovation and evaluation will be required to improve recruitment to clinical trials.. EU Clinical Trials Register. EudraCT Number: 2011-001883-23 . ISRCTN registry.  ISRCTN72443278 .

Topics: Aged; Allopurinol; Audiovisual Aids; Febuxostat; Female; Gout; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Patient Education as Topic; Patient Selection

To examine whether allopurinol dose escalation to achieve serum urate (SU) target can influence bone erosion or monosodium urate (MSU) crystal deposition, as measured by dual-energy computed tomography (DECT) in patients with gout.. We conducted an imaging study of a 2-year randomized clinical trial that compared immediate allopurinol dose escalation to SU target with conventional dosing for 1 year followed by dose escalation to target, in gout patients who were receiving allopurinol and who had an SU level of ≥0.36 mmoles/liter. DECT scans of feet and radiographs of hands and feet were obtained at baseline, year 1, and year 2 visits. DECT scans were scored for bone erosion and urate volume.. Paired imaging data were available for 87 patients (42 in the dose-escalation group and 45 in the control group). At year 2, the progression in the CT erosion score was higher in the control group than in the dose-escalation group (+7.8% versus +1.4%; P = 0.015). Changes in plain radiography erosion or narrowing scores did not differ between groups. Reductions in DECT urate volume were observed in both groups. At year 2, patients in the control group who had an SU level of <0.36 mmoles/liter and patients in the dose-escalation group had reduced DECT urate volume (-27.6 to -28.3%), whereas reduction in DECT urate volume was not observed in control group patients with an SU level of ≥0.36 mmoles/liter (+1.5%) (P = 0.023).. These findings provide evidence that long-term urate-lowering therapy using a treat-to-SU-target strategy can influence structural damage and reduce urate crystal deposition in gout.

Topics: Aged; Allopurinol; Bone Resorption; Dose-Response Relationship, Drug; Female; Foot Bones; Foot Joints; Gout; Gout Suppressants; Hand Bones; Hand Joints; Humans; Male; Middle Aged; Tomography, X-Ray Computed; Treatment Outcome; Uric Acid

Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.. We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).. In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.. In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

Topics: Aged; Allopurinol; Cardiovascular Diseases; Cause of Death; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged

Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a "treat-to-target" strategy congruent with specialty guidelines.. We have planned and initiated the Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind, non-inferiority trial will enroll 950 gout patients randomized to receive allopurinol or febuxostat. Patients will be followed for a total of 72 weeks encompassing 3 distinct 24-week study phases. During Phase I (0-24 weeks), participants will undergo gradual dose titration of ULT until achievement of serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose escalation will not be allowed during final three study visits of Phase 2 (24-48 weeks) and during Phase 3 (48-72 weeks). The primary study outcome is the proportion of participants experiencing at least one gout flare during Phase 3. Subsequent to the 72-week study, participants will be followed passively for up to 10 years after the study to assess long-term health outcomes.. With its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study will demonstrate the central role of gradual ULT dose escalation and a treat-to-target strategy in gout management.

Topics: Adult; Allopurinol; Dose-Response Relationship, Drug; Double-Blind Method; Drug Dosage Calculations; Drug Monitoring; Febuxostat; Gout; Gout Suppressants; Humans; Male; Medication Therapy Management; Middle Aged; Practice Guidelines as Topic; Treatment Outcome; United States; United States Department of Veterans Affairs; Uric Acid; Veterans Health

The objective of the study was to evaluate the effect of lesinurad, a selective uric acid uptake inhibitor, alone and in combination with the xanthine oxidase inhibitor allopurinol, on serum uric acid and urinary urate excretion in patients with gout and hyperuricemia. A phase 1b, multicenter, open-label, multiple-dose study was carried out in patients with gout with serum uric acid ≥8 mg/dL following washout of urate-lowering therapy. Patients were treated with allopurinol 300 mg/day alone in week 1; lesinurad 400 or 600 mg/day was added in week 2, followed by lesinurad 400 or 600 mg/day alone in week 3. Serum uric acid and urine uric acid were evaluated each week. Safety was assessed throughout the study. Lesinurad 400 or 600 mg/day added to allopurinol 300 mg/day reduced serum uric acid by 60% and 72%, respectively, versus allopurinol alone (37%) or lesinurad 400 mg/day (44%) or 600 mg/day (47%) alone. A 100% response rate of serum uric acid <6 mg/dL was achieved by all combinations (serum uric acid <5 mg/dL by 50%-90%). Mean 24-hour urate excretion compared with baseline was -35% with allopurinol, +36% and +56.5% with lesinurad 400 mg/day and 600 mg/day, respectively, and -11.6% and -7.1% with the respective combination therapies. Treatments were well tolerated. In this phase 1 trial, lesinurad added to allopurinol resulted in greater serum uric acid reduction than did allopurinol or lesinurad monotherapy.

Topics: Adult; Allopurinol; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Thioglycolates; Triazoles; Uric Acid

Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of hyperuricemia and gout. This phase 1b, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in combination with allopurinol. Adult males with gout were randomized to receive once-daily oral doses of allopurinol 300 mg or verinurad 10 mg alone for 7 days, allopurinol 300 mg + verinurad 10 mg on days 8 to 14, and the alternative single agent on days 15 to 21. Colchicine 0.6 mg was taken prophylactically for gout flares. Plasma/serum and urine samples were assayed for verinurad, allopurinol, oxypurinol (allopurinol active metabolite), colchicine (plasma only), and uric acid. Safety was assessed by adverse events (AEs) and laboratory tests. Verinurad plasma exposure was unaffected by allopurinol. Verinurad increased the maximum observed plasma concentration (C

Topics: Adolescent; Adult; Aged; Allopurinol; Area Under Curve; Drug Administration Schedule; Gout; Gout Suppressants; Humans; Male; Middle Aged; Naphthalenes; Oxypurinol; Propionates; Pyridines; Uric Acid; Young Adult

To determine factors that predict inadequate serum urate (SU) lowering response in a randomized controlled trial of allopurinol dose escalation (DE) in gout.. Participants undergoing allopurinol DE were classified as: complete response (CR)-reached target SU at month 9 and 12 of the DE phase or if still dose escalating at month 9 reached target SU by month 12; partial response (PR)-reached target at some stage but not fulfilling criteria for CR; or inadequate response (IR)-did not reach target SU at any time.. IR was uncommon, occurring in 13/150 (8.7%), compared with 82 (54.7%) CR, and 55 (36.6%) PR. Mean (s.e.m.) SU was higher at the end of the 12-month DE in IR compared with both CR and PR groups; 7.6 (0.31) vs 5.01 (0.06) and 5.97 (0.17) mg/dl respectively (P < 0.001). In univariate analysis, compete responders tended to be older, be receiving less allopurinol, have longer gout duration and were more likely to be New Zealand (NZ) European ethnicity, compared with IR+PR. Using multi-variate logistic regression analysis, only longer duration of gout and NZ European ethnicity remained significant independent predictors of CR. Baseline SU ⩾ 8 mg/dl had a sensitivity of 69.2% and specificity of 85.1% in predicting IR. The odds ratio for an IR if baseline SU was ⩾8 mg/dl was 11.7 (95% CI 3.3, 41.2).. A minority of people with gout never reach target SU when allopurinol dose is increased in a treat-to-target manner. Approximately one-third of those with SU ⩾ 8mg/dl despite allopurinol ⩾300mg/d have an IR to DE.. Australian New Zealand Clinical Trails Registry, https://www.anzctr.org.au, ACTRN12611000845932.

Topics: Allopurinol; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Treatment Outcome; Uric Acid

The aim of this research work was to observe and analyze the efficacy of febuxostat and allopurinol in the treatment of gout with hyperuricemia. The 160 patients who has been diagnosed with gout and hyperuricemia in our hospital were selected as research objects. They were randomly divided into research group and control group, each containing 80. The control group received conventional allopurinol treatment, while the research group was treated with febuxostat. Then, the treatment efficacy was compared between the two groups. Through comparison of blood uric acid levels between the two groups after treatment, it can be known that improvement was more significant in the research group, P<0.05. The adverse reaction rate in the research group was significantly lower, P<0.05. For patients with gout and hyperuricemia, febuxostat therapy has better efficacy than that of allopurinol.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Double-Blind Method; Drug Therapy, Combination; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Treatment Outcome; Uric Acid

In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community.. Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 μmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346.. 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 μmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years.. Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes.. Arthritis Research UK.

Topics: Aged; Allopurinol; Cost-Benefit Analysis; Disease Management; England; Female; General Practice; Gout; Gout Suppressants; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Practice Patterns, Nurses'; Quality-Adjusted Life Years; Surveys and Questionnaires; Uric Acid

Allopurinol dosing has frequently been limited based on creatinine clearance (CrCL), resulting in failure to achieve target serum urate (SU). The aim of this analysis was to determine how many milligrams of allopurinol above the recommended CrCL-based dose (R+) are required to achieve target SU and to investigate the factors that influence R+.. We analysed data from participants in a 24-month open, randomized, controlled, parallel-group, comparative clinical trial. Data obtained during the 12-month dose escalation (DE) phase of the study (year 1 for DE/DE and year 2 for control/DE) were combined. R+ dose was defined as the number of milligrams of allopurinol above the CrCL-based dose at the final visit.. Of the 132 participants, R+ allopurinol dose at the final visit was ≤ 100 mg/day in 38 (28.8%), 101-200 mg/day in 46 (34.8%) and > 200 mg/day in 48 participants (37.1%). There was no significant difference between the R+ groups in the number of participants achieving target SU. There was an increase in plasma oxypurinol and a larger percentage and absolute change in SU as R+ increased. Multivariate analysis revealed CrCL, weight, baseline SU and allopurinol dose, were significantly positively associated with allopurinol dose at 12 months. There were no significant differences across R+ groups in renal or liver function adverse events, although there were numerically more serious adverse events in the higher R+ groups.. A wide range of R+ doses are required to achieve target SU. Four easily obtained clinical variables (baseline SU, CrCL, weight, and allopurinol dose) may be helpful to predict allopurinol dose.. ANZCTR, ACTRN12611000845932 . Registered on 10 August 2011.

Topics: Adult; Aged; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; Gout; Gout Suppressants; Humans; Male; Metabolic Clearance Rate; Middle Aged; Uric Acid

To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach.. A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs).. 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups.. Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated.. ANZCTR12611000845932; Results.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Allopurinol; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; gamma-Glutamyltransferase; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Care Planning; Treatment Outcome; Uric Acid

To determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.. People, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24.. The mean (SE) change in SU from month 12 to 24 was -1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups.. The majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment.. ACTRN12611000845932.

Topics: Aged; Allopurinol; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Time Factors; Treatment Outcome; Uric Acid

To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study.. Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible for an open-label, uncontrolled extension study of lesinurad 400 mg monotherapy.. Patients (n = 214) were primarily white males (mean age 54.4 years; gout duration 11.2 years). Significantly more patients achieved the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001). Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely. No new safety findings were observed in the extension.. In patients with gout and intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo, with sustained effects for up to 18 months. Due to a high incidence of serum creatinine elevations and renal-related adverse events, including serious adverse events with lesinurad 400 mg, lesinurad should not be used as monotherapy.. ClinicalTrials.gov (http://clinincaltrials.gov), NCT01508702.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Resistance; Enzyme Inhibitors; Female; Gout; Humans; Male; Middle Aged; Thioglycolates; Treatment Outcome; Triazoles; Uricosuric Agents; Xanthine Oxidase; Young Adult

Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, 'smartphone' application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT.. Setting and designPrimary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial.. GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster.. The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary.. The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed 'dropout' rate 20%.. This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferences and peer-reviewed journal.. ACTRN12616000455460.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Internet; Patient Compliance; Prospective Studies; Quality of Life; Research Design; Self-Management; Uric Acid

The use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management. The aim of this study was to determine the effect of baseline kidney function on safety and efficacy of allopurinol dose escalation to achieve serum urate (SU) <6 mg/dl.. We undertook a post hoc analysis of a 24-month allopurinol dose escalation treat-to-target SU randomized controlled trial, in which 183 people with gout were randomized to continue current dose allopurinol for 12 months and then enter the dose escalation phase or to begin allopurinol dose escalation immediately. Allopurinol was increased monthly until SU was <6 mg/dl. The effect of baseline kidney function on urate lowering and adverse effects was investigated.. Irrespective of randomization, there was no difference in the percentage of those with creatinine clearance (CrCL) <30 ml/min who achieved SU <6 mg/dl at the final visit compared to those with CrCL ≥30 to <60 ml/min and those with CrCL ≥60 ml/min, with percentages of 64.3% vs. 76.4% vs. 75.0%, respectively (p = 0.65). The mean allopurinol dose at month 24 was significantly lower in those with CrCL <30 ml/min as compared to those with CrCL ≥30 to <60 ml/min or CrCL ≥60 ml/min (mean (SD) 250 (43), 365 (22), and 460 (19) mg/day, respectively (p < 0.001)). Adverse events were similar among groups.. Allopurinol is effective at lowering urate even though and accepting that there were small numbers of participants with CrCL <30 ml/min, these data indicate that allopurinol dose escalation to target SU is safe in people with severe CKD. The dose required to achieve target urate is higher in those with better kidney function.. Australian and New Zealand Clinical trials Registry, ACTRN12611000845932 . Registered on 10 August 2011.

Topics: Adult; Aged; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Uric Acid

Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects.. FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test.. Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours.. These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout.

Topics: Adult; Aged; Female; Gout; Gout Suppressants; Healthy Volunteers; Humans; Hyperuricemia; Kidney; Male; Middle Aged; Uric Acid; Xanthine Oxidase; Young Adult

Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl.. Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data.. The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels.. Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Double-Blind Method; Drug Combinations; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Thioglycolates; Triazoles; United States; Uricosuric Agents; Young Adult

Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.. Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.. Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.. Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.. NCT01493531.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Creatinine; Double-Blind Method; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency; Retreatment; Symptom Flare Up; Thioglycolates; Triazoles; Uric Acid; Uricosuric Agents; Young Adult

Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose-response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose-response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be -44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose-response relationship in Japanese hyperuricemic patients with or without gout.

Topics: Adult; Allopurinol; Double-Blind Method; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Nitriles; Pyridines; Treatment Outcome; Uric Acid; Young Adult

The effect of gout on the risk of developing coronary artery disease (CAD) is uncertain. Some studies have found that gout is a risk factor for acute myocardial infarction. This study examined the changes in risk of CAD in gout patients taking allopurinol and/or benzbromarone, and analyzed the dose-response relationship of both drugs with CAD incidence.. The medical records of one million subjects from 2000 to 2011 were provided by the Taiwan National Health Insurance Research Database. Cox proportional hazard ratio was used to compare the risk of CAD in gout patients taking allopurinol or/and benzbromarone with those taking neither drug. Hazard ratios (HR) were adjusted for possible confounding factors, including age, gender, hypertension, hyperlipidemia, diabetes mellitus, chronic kidney disease, and relevant medications.. Of 8047 gout patients, 1422 were treated with allopurinol (Group A), 4141 with benzbromarone (Group B), and 2484 with both drugs (Group A/B) during the follow-up period. Our results showed the incidence of CAD after adjusting for covariates for Group A, Group B, and Group A/B did not significantly differ from the comparison group. However, after adjustment for covariates in dose-response analyses, treatment with over 270 defined daily doses (DDDs) of allopurinol, and over 360 DDDs of benzbromarone, was associated with a significantly reduced risk of CAD.. We found that the use of allopurinol and benzbromarone, whether alone or in combination, had a linear dose-response relationship between the numbers of defined daily doses and the risk of CAD, especially in higher DDDs.

Topics: Allopurinol; Benzbromarone; Coronary Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Population Surveillance; Risk Factors; Taiwan; Treatment Outcome; Uric Acid; Uricosuric Agents

To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol.. Patients (N=227) with an inadequate response to allopurinol, defined as serum urate (sUA) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol, were randomised 2:1 to 4 weeks of double-blind treatment with lesinurad (200, 400 or 600 mg/day) or matching placebo in combination with their prestudy allopurinol dose (200-600 mg/day). Colchicine prophylaxis for gout flares was required. The primary end point was percent reduction from baseline sUA levels at 4 weeks. A pharmacokinetic substudy was also conducted. Safety was assessed throughout.. Patients (n=208) received ≥1 dose of blinded medication. Lesinurad 200, 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with placebo (p<0.0001, all doses vs placebo). Similar results were observed in patients with mild or moderate renal insufficiency (estimated creatinine clearance 30 to <90 mL/min). The incidence of ≥1 treatment-emergent adverse event was 46%, 48% and 54% with lesinurad 200, 400 and 600 mg, respectively, and 46% with placebo (most frequent, gout flares, arthralgia, headache and nasopharyngitis), with no deaths or serious adverse events.. Lesinurad achieves clinically relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone.. NCT01001338.

Topics: Adult; Allopurinol; Double-Blind Method; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Thioglycolates; Treatment Outcome; Triazoles

This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative.. Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs).. Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs.. Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative.

Topics: Administration, Oral; Adult; Alleles; Allopurinol; China; Febuxostat; Female; Gout; Gout Suppressants; HLA-B Antigens; Humans; Hyperuricemia; Male; Middle Aged; Treatment Outcome; Uric Acid

Arhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout.. This was a 12-week, randomized, double-blind, controlled phase IIb study. Eligible patients had had ≥3 flares of gout during the previous year, had discontinued urate-lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5-12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure.. A total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were -12.5% with 600 mg arhalofenate and -16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus -0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5-fold the baseline value were observed in the arhalofenate-treated groups.. Arhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate-lowering antiflare therapy.

Topics: Acetamides; Allopurinol; Double-Blind Method; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Phenylacetates; Treatment Outcome

Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan.. An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period.. Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups.. Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy.. http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Neoplasms; Thiazoles; Tumor Lysis Syndrome; Uric Acid; Xanthine Oxidase; Young Adult

In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout.. We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit.. One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day (P < 0·001, Jonckheere-Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was -30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of -32·4% ([95% confidence interval, -38·9% to -25·9%]; P < 0·001). Incidences of overall adverse events (AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups.. A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Nitriles; Pyridines; Treatment Outcome; Uric Acid; Xanthine Oxidase

The objective of these clinical studies was to assess the safety and urate lowering activity of a novel urate transporter 1 (URAT1)/ xanthine oxidase (XO) inhibitor PF-06743649 in healthy subjects and gout patients. Escalating doses of PF-06743649 or placebo were given to healthy young subjects, healthy elderly subjects and gout patients. Serum uric acid (sUA) and urinary pharmacodynamic markers were assayed, and safety was assessed by collection of adverse events and assessment of safety labs, ECGs and vital signs. Administration of PF-06743649 led to rapid decrease in sUA in all cohorts; in gout patients, a change from baseline of 69 % was observed for the 40 mg dose. Urinary and serum biomarkers were consistent with inhibition of both URAT1 and XO. Although dosing was otherwise well tolerated, two subjects experienced serious adverse events of acute kidney injury. Both subjects exhibited increased serum creatinine and blood urea nitrogen in the first 3 days post first dose and were hospitalised. One subject exhibited oliguria for the first 24 h. Both subjects made a complete recovery with minimal intervention. PF-06743649 was effective at rapidly lowering sUA, but further development was terminated for an identified renal safety risk.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Double-Blind Method; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Organic Anion Transporters; Organic Cation Transport Proteins; United States; Uric Acid; Xanthine Oxidase; Young Adult

There are no clinical reports that have compared topiroxostat, a selective xanthine oxidase inhibitor, with allopurinol in serum urate-lowering efficacy. The aim of this study was to compare the efficacy and safety of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout.. A phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study conducted in Japan. Patients who had inadequate serum urate levels (a gout patient: serum urate level ≥416·4 μmol/L; an asymptomatic hyperuricemic patient with specific complications (urinary lithiasis, hypertension, hyperlipidemia and/or diabetes): serum urate level ≥475·8 μmol/L; and an asymptomatic hyperuricemic patient with no specific complications: serum urate level ≥535·3 μmol/L) were randomized to topiroxostat 120 mg/day or allopurinol 200 mg/day, with an equal allocation ratio, for 16 weeks. To prevent the onset of gouty arthritis by rapid serum urate reduction, these doses were increased in a stepwise manner. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit.. Overall, 206 patients were randomly assigned to topiroxostat and allopurinol. Two hundred and three patients (allopurinol: n = 105, topiroxostat: n = 98) received at least one dose of the study drug and had their serum urate level assessed at least once. The baseline characteristics were comparable between groups. The mean age of patients was 53·0 ± 11·4 years and 99% of patients were male. The primary efficacy endpoint was -34·3 ± 11·1% in the allopurinol group (n = 105) and -36·3 ± 12·7% in the topiroxostat group (n = 98). Non-inferiority of the serum urate-lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin (95% confidence interval, -5·3 to 1·3%). The overall incidences of adverse events and adverse drug reactions were similar between both groups.. Topiroxostat 120 mg/day provides non-inferior serum urate reduction compared with allopurinol 200 mg/day and is well tolerated in Japanese hyperuricemic patients with or without gout.

Topics: Adult; Aged; Allopurinol; Double-Blind Method; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Nitriles; Pyridines; Treatment Outcome; Uric Acid; Xanthine Oxidase

Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment.. To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA<6.0mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently.. Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients.

Topics: Allopurinol; Ambulatory Care; Automation; Gout; Gout Suppressants; Humans; Patient Education as Topic; Pharmacists; Research Design; Telephone; Uric Acid

This study aims to investigate the influence of dietary education in patients with gout on a stable dose of urate-lowering therapy (ULT).. Males and females aged >18 years with a history of gout, receiving an appropriate and stable dose of ULT, were recruited from two tertiary hospitals and randomised into two groups. The control group received basic advice regarding the importance of compliance with therapy and the benefit of weight loss. The intervention group received comprehensive dietary advice based on the British Society of Rheumatology Guidelines. Both groups received education at baseline and 3 months. Serum urate was measured at baseline, 3 months and 6 months, and a questionnaire was completed at baseline and at 6 months. The primary outcome of the study was to compare the change in serum urate between groups.. Thirty patients were recruited into the study. There was no difference in serum urate between the control and intervention group at 6 months (0.29 mmol/L vs 0.29 mmol/L at baseline and 0.27 mmol/L vs 0.30 mmol/L at 6 months). The intervention group showed a statistically significant improvement in knowledge (8/13 in control group at baseline to 9/13 at 6 months vs 8/13 in intervention group at baseline to 12/13 at 6 months, P < 0.05) and self-reported dietary modification (1 in control vs 7 in intervention P < 0.05) at 6 months.. This randomised controlled trial shows that in patients on ULT, providing education on diet does not lead to any clinically significant difference in serum urate at 6 months.

Topics: Adult; Aged; Allopurinol; Australia; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Patient Satisfaction; Prognosis; Prospective Studies; Recurrence; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Uric Acid

Traditionally, allopurinol is not initiated during an acute gout attack to avoid prolonging the painful arthritis. The 2012 American College of Rheumatology Guidelines for the Management of Gout suggest that urate-lowering therapy can be started during an acute attack, based on "consensus opinion of experts, case studies, or standard of care.". The aim of this study was to determine whether initiating allopurinol will adversely affect the resolution of acute, treated gout.. We conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients with acute gout. Patients with crystal-proven gout by arthrocentesis were enrolled if they presented to the rheumatology clinic with an acute gout attack within 72 hours from initial therapy. The patients were also required to meet at least 1 additional criterion for urate-lowering therapy including (1) the presence of gouty tophi, (2) more than 1 acute gout attack per year, (3) a history of nephrolithiasis, or (4) urate overproduction (>1000 mg in 24-hour urine collection). Patients were excluded from the study if they had a glomerular filtration rate of less than 50 or liver function test of greater than 1.25 times the upper limit of normal. The treating physician determined therapy for the acute gout attack. Standard prophylaxis, with colchicine or nonsteroidal anti-inflammatory drugs, was prescribed. Allopurinol or placebo was initiated at 100 mg daily for the first 14 days and then increased to 200 mg daily for the next 14 days. The primary end point was protocol defined days to resolution of acute gout, incorporating patient-rated joint pain and physician examination. Secondary measures included Physician Global Assessment, patient-rated pain, adverse effects of therapy, and serum uric acid.. Thirty-one patients (17 on placebo, 14 on allopurinol) completed the study. Both intent-to-treat and completer analyses showed only a statistically insignificant difference in days to resolution (15.4 days in the allopurinol group completers vs 13.4 days in the placebo group; P = 0.5). The secondary measures revealed that the acute phase of pain rapidly improved in both groups.. We initiated allopurinol at low doses during an acute gout attack in patients who met criteria for starting urate-lowering therapy and did not have abnormal kidney or liver function. In this cohort, allopurinol did not prolong the acute, treated attack.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Time Factors; Treatment Outcome; Uric Acid

Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes.. We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5] mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P=0.36).. In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987415.

Topics: Aged; Allopurinol; Biomarkers; Diuretics; Double-Blind Method; Endpoint Determination; Exercise Test; Exercise Tolerance; Female; Gout; Gout Suppressants; Heart Failure; Hospitalization; Humans; Hyperuricemia; Male; Middle Aged; Oxidative Stress; Quality of Life; Stroke Volume; Surveys and Questionnaires; Treatment Outcome; Ultrasonography; Xanthine Oxidase

To compare the efficiency and safety of febuxostat with those of allopurinol in Chinese patients with gout and hyperuricemia.. The trial which was conducted at 13 centers in China during 2011-2013 included a 2-week run-in and a 24-week treatment period. A total of 504 eligible participants with gout and with serum urate ≥ 480 μmol/L were randomly assigned 1 : 1 : 1 to febuxostat 40 mg/day, febuxostat 80 mg/day and allopurinol 300 mg/day groups. The primary efficacy endpoint was the percentage of subjects whose last three serum urate levels were < 360 μmol/L.. The primary efficacy endpoint was reached by 33.5% of subjects taking febuxostat 80 mg/day, 22.5% of those taking febuxostat 40 mg/day and 17.0% of those taking allopurinol 300 mg/day (P < 0.001 for the comparison between febuxostat 80 mg/day and allopurinol 300 mg/day groups; P = 0.216 for the comparison between febuxostat 40 mg/day and allopurinol 300 mg/day groups). The incidence of gout flare was relatively high in each group during the first 8 weeks and gradually decreased thereafter. There was no statistically significant difference between the three groups (P > 0.05). The incidence of adverse events was similar in the three treatment groups. The most frequent treatment-related adverse events were liver function test abnormalities.. Febuxostat 80 mg/day had superior urate-lowering efficacy to that of febuxostat 40 mg/day or allopurinol 300 mg/day, which was comparable in Chinese gout patients with hyperuricemia. Febuxostat, at a daily dose of 40 or 80 mg, was safe and well tolerated.

Topics: Administration, Oral; Adult; Allopurinol; Biomarkers; China; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Time Factors; Treatment Outcome; Uric Acid

Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses.. Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency.. Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0mg/dL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 48.3% in dosing categories < 300, 300, and > 300 mg, respectively.. This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

Topics: Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Treatment Outcome; Uric Acid

To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil.. We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology.. Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%.. This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Colchicine; Drug Therapy, Combination; Female; Gout; Guideline Adherence; Humans; Male; Middle Aged; Rheumatology; Societies, Medical

We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid-femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤ 360 μmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.

Topics: Aged; Allopurinol; Biomarkers; Chronic Disease; Enzyme Inhibitors; Febuxostat; Germany; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Inflammation Mediators; Kidney; Male; Middle Aged; Oxidative Stress; Prospective Studies; Pulse Wave Analysis; Severity of Illness Index; Thiazoles; Time Factors; Treatment Outcome; Uric Acid; Vascular Stiffness; Xanthine Oxidase

Topiroxostat, a selective xanthine oxidase inhibitor, shows effective reduction in the serum urate level in hyperuricemic patients with or without gout. The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout.. The study design was a 22-week, randomized, multicenter, double-blind study. The enrolled patients were randomly assigned to treatment with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints were the percent change in the serum urate level, change in the estimated glomerular filtration rate, the urinary albumin-to-creatinine ratio, the proportion of patients with serum urate levels of 356.88 μmol/L or less, blood pressure, and serum adiponectin.. After 22 weeks, although the changes in the estimated glomerular filtration rate and blood pressure were not significant, the percent change in the serum urate level (-45.38 vs. -0.08 %, P < 0.0001) and the percent change in urinary albumin-to-creatinine ratio (-33.0 vs. -6.0 %, P = 0.0092) were found to have decreased in the topiroxostat as compared with the placebo. Although the incidence of 'alanine aminotransferase increased' was higher in the topiroxostat, serious adverse event rates were similar in the two groups.. Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.

Topics: Adiponectin; Aged; Albuminuria; Blood Pressure; Comorbidity; Creatinine; Double-Blind Method; Enzyme Inhibitors; Female; Glomerular Filtration Rate; Gout; Humans; Hyperuricemia; Male; Middle Aged; Nitriles; Prevalence; Pyridines; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid; Xanthine Oxidase

Febuxostat, a novel non-purine selective inhibitor of xanthine oxidase, has been identified as a potential alternative to allopurinol in patients with hyperuricemia. The purpose of this study was to compare the urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in Chinese gout patients with hyperuricemia.. Gout patients (n = 512) with serum uric acid (sUA) concentrations of at least 8.0 mg/dL were randomized to receive daily febuxostat 40 mg or 80 mg or allopurinol 300 mg for 28 weeks. Prophylaxis against gout flares with meloxicam or colchicine was provided during weeks 1 through 8. The primary endpoint was the percentage of subjects achieving a sUA concentration of <6.0 mg/dL at the last three monthly measurements.. The primary endpoint was reached in 44.77% of patients receiving 80 mg of febuxostat, 27.33% of those receiving 40 mg of febuxostat, and 23.84% of those receiving allopurinol. The UL efficacy in the febuxostat 80 mg group was higher than in the allopurinol (P < 0.0001) and febuxostat 40 mg (P = 0.0008) groups. The UL efficacy of the febuxostat 40 mg group was statistically non-inferior to that of the allopurinol group. No significant change in the number of tophi was observed during the final visit relative to baseline in each treatment group. The rate of gout flares requiring treatment from weeks 9 through 28 and the incidence of adverse events was similar among treatment groups.. The UL efficacy of daily febuxostat 80 mg was greater than that of febuxostat 40 mg and allopurinol 300 mg, which exhibited comparable UL efficacy. Safety of febuxostat and allopurinol was comparable at the doses tested.

Topics: Adult; Allopurinol; Biomarkers; China; Double-Blind Method; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Remission Induction; Thiazoles; Time Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

The aims of this study were to establish whether, in patients with gout, MPO is released from neutrophils and urate is oxidized to allantoin and if these effects are attenuated by allopurinol.. MPO, urate, allantoin and oxypurinol were measured in plasma from 54 patients with gout and 27 healthy controls. Twenty-three patients had acute gout, 13 of whom were receiving allopurinol, and 31 had intercritical gout, 20 of whom were receiving allopurinol. Ten additional gout patients had samples collected before and after 4 weeks of allopurinol.. Plasma MPO and its specific activity were higher (P < 0.05) in patients with acute gout not receiving allopurinol compared with controls. MPO protein in patients' plasma was related to urate concentration (r = 0.5, P < 0.001). Plasma allantoin was higher (P < 0.001) in all patient groups compared with controls. In controls and patients not receiving allopurinol, allantoin was associated with plasma urate (r = 0.62, P < 0.001) and MPO activity (r = 0.45, P < 0.002). When 10 patients were treated with allopurinol, it lowered their plasma urate and allantoin (P = 0.002). In all patients receiving allopurinol, plasma allantoin was related to oxypurinol (r = 0.65, P < 0.0001). Oxypurinol was a substrate for purified MPO that enhanced the oxidation of urate.. Increased concentrations of urate in gout lead to the release of MPO from neutrophils and the oxidation of urate. Products of MPO and reactive metabolites of urate may contribute to the pathology of gout and hyperuricaemia. At low concentrations, oxypurinol should reduce inflammation, but high concentrations may contribute to oxidative stress.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Enzyme-Linked Immunosorbent Assay; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Mass Spectrometry; Middle Aged; Oxidation-Reduction; Oxidative Stress; Peroxidase; Uric Acid

Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).. FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3.. FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.. FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Prospective Studies; Research Design

The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.

Topics: Allopurinol; Biomarkers; Blood Pressure; Creatinine; Dose-Response Relationship, Drug; Febuxostat; Gout; Gout Suppressants; Humans; Hypertension, Renal; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Thiazoles; Treatment Outcome

To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial.. Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO), rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16.. The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P ≤ 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%). Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths.. Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with >70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile.. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00958438.

Topics: Adult; Allopurinol; Double-Blind Method; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Medication Adherence; Middle Aged; Receptors, Interleukin-1 Type I; Recombinant Fusion Proteins; Treatment Outcome; Uric Acid

Studies in human volunteers have shown that vitamin C reduces serum urate (SU) levels. The aim of this study was to determine the effects of vitamin C on SU levels in patients with gout.. Patients with gout and an SU level >0.36 mmoles/liter (6 mg/dl) were recruited. Twenty patients already taking allopurinol were randomized to receive an increase in the dose of allopurinol or to commence taking vitamin C (500 mg/day). Twenty patients who had not been taking allopurinol were randomized to start receiving either allopurinol (up to 100 mg/day) or vitamin C (500 mg/day). Levels of plasma ascorbate, creatinine, and SU were measured on day 0 and week 8.. There was no significant difference in the baseline SU level or estimated glomerular filtration rate (eGFR) between those who received vitamin C and those who did not (for SU, mean ± SEM 0.50 ± 0.11 mmoles/liter [8.4 ± 1.8 mg/dl] versus 0.50 ± 0.09 mmoles/liter [8.4 ± 1.5 mg/dl]; for eGFR, mean ± SEM 65.5 ± 3.5 ml/minute/1.73 m(2) versus 67.9 ± 4.6 ml/minute/1.73 m(2) ). Among the randomized patients, 30% in the vitamin C group and 25% in the no vitamin C control group were receiving diuretics. In the patients receiving vitamin C, there was a significant increase between day 0 and week 8 in the plasma ascorbate level. The reduction in SU level over 8 weeks was significantly less in those patients receiving vitamin C compared to those who started or increased the dose of allopurinol (mean reduction 0.014 mmoles/liter [0.23 mg/dl] versus 0.118 mmoles/liter [1.9 mg/dl]; P < 0.001).. A modest dosage of vitamin C (500 mg/day) for 8 weeks had no clinically significant urate-lowering effects in patients with gout, despite the fact that plasma ascorbate levels increased. These results differ from previous findings in healthy control subjects with hyperuricemia. The uricosuric effect of modest-dose vitamin C appears to be small in patients with gout, when administered as monotherapy or in combination with allopurinol.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Ascorbic Acid; Creatinine; Dietary Supplements; Female; Gout; Humans; Male; Middle Aged; New Zealand; Pilot Projects; Treatment Outcome; Uric Acid

Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents.. Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial.. Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m²) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events.. Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Body Mass Index; Cohort Studies; Comorbidity; Diabetes Complications; Dose-Response Relationship, Drug; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Intention to Treat Analysis; Kidney; Lost to Follow-Up; Male; Middle Aged; Obesity; Patient Dropouts; Renal Insufficiency; Thiazoles; Xanthine Oxidase; Young Adult

Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.. Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.. Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).. Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.. NCT00325195, NCT01356498.

Topics: Adult; Aged; Allopurinol; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Polyethylene Glycols; Time Factors; Treatment Outcome; Urate Oxidase; Uric Acid

Many doctors believe that patients with gout are unwilling to receive urate-lowering therapy (ULT) and blame them for poor adherence to management.. To test the effectiveness of a complex intervention for gout that incorporates key elements of current guidelines, including full patient information, delivered in an optimal setting (specialist hospital clinic).. Observational study of patients reporting ongoing attacks of gout recruited from primary care lists. 106 participants (94 men, 12 women; mean age 61 years) were enrolled in the study. Patients received a predominantly nurse-delivered intervention that included education, individualised lifestyle advice and appropriate ULT. The predefined goal was to achieve serum uric acid (SUA) levels≤360 μmol/l after 1 year in at least 70% of participants.. Of the 106 participants at baseline, 16% had tophi; mean (SD) baseline SUA was 456 (98) µmol/l. All participants agreed to joint aspiration to confirm gout and all wished to receive ULT. At 12 months, 92% of the 106 participants had achieved the therapeutic target (SUA≤360 µmol); 85% had SUA<300 µmol/l. Allopurinol was the most commonly used ULT, requiring a median dose of 400 mg daily to achieve the target. Improvements in Short Form-36 were observed (significant for pain) after 1 year.. A predominantly nurse-led intervention including education, lifestyle advice and ULT can successfully achieve the recommended treatment target in more than 9 out of 10 patients. Full explanation and discussion about the nature of gout and its treatment options and individualisation of management probably account for this success.

Topics: Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Practice Patterns, Nurses'; Risk Reduction Behavior; Treatment Outcome; Uric Acid

Hyperuricemia can accelerate renal decline associated with aging. Chronic kidney disease is frequently seen in patients with hyperuricemia and gout.. Assess the impact of urate-lowering therapy on renal function in subjects with gout who were treated with febuxostat for ≤ 48 months.. Subjects from 2 phase 3 clinical studies were enrolled in the phase 3, long-term, open-label Febuxostat/Allopurinol Comparative Extension Long-Term (EXCEL) study. In the EXCEL study, 1086 subjects initially were treated with febuxostat 80 or 120 mg daily, or allopurinol 300 mg daily. The subjects were permitted to switch between doses of febuxostat and/or allopurinol during the first 6 months of treatment to achieve and maintain a serum uric acid (SUA) level ≥ 3 to < 6 mg/dL. For the analysis presented in this article, data from 551 subjects who received only febuxostat throughout the duration of both the phase 3 and EXCEL studies (≤ 48 months) were used to determine the impact of SUA reduction on estimated glomerular filtration rates (eGFRs).. At baseline of the 2 original phase 3 studies, subjects' mean SUA level was 9.8 mg/dL. Greater sustained decreases in subjects' SUA levels were associated with less renal function decline (P < 0.001) by statistical modeling. The study data predicted that for every 1 mg/dL of chronic reduction of SUA level in subjects with gout, there would be a preservation of 1.15 mL/min of eGFR.. Sustained urate-lowering therapy with febuxostat appears to impede renal decline in patients with gout. The results discussed in this article support similar observations previously reported in 116 hyperuricemic subjects with gout who received febuxostat for ≤ 5 years.

Topics: Adult; Aged; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney; Kidney Function Tests; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid

To compare the characteristics of female versus male gout patients and assess urate-lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.. This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate-lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function.. Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate-lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea.. These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Comorbidity; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Illinois; Male; Metabolic Diseases; Middle Aged; Obesity; Retrospective Studies; Sex Factors; Thiazoles; Treatment Outcome; Uric Acid; Young Adult

To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy.. In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained.. Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015).. The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

Topics: Allopurinol; Double-Blind Method; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Injections, Subcutaneous; Male; Middle Aged; Recombinant Fusion Proteins; Treatment Outcome

African Americans are twice as likely as Caucasians to develop gout, but they are less likely to be treated with urate-lowering therapy (ULT). Furthermore, African Americans typically present with more comorbidities associated with gout, such as hypertension, obesity, and renal impairment. We determined the efficacy and safety of ULT with febuxostat or allopurinol in African American subjects with gout and associated comorbidities and in comparison to Caucasian gout subjects.. This is a secondary analysis of the 6-month Phase 3 CONFIRMS trial. Eligible gouty subjects with baseline serum urate (sUA) ≥ 8.0 mg/dL were randomized 1:1:1 to receive febuxostat 40 mg, febuxostat 80 mg, or allopurinol (300 mg or 200 mg depending on renal function) daily. All subjects received gout flare prophylaxis. Primary efficacy endpoint was the proportion of subjects in each treatment group with sUA < 6.0 mg/dL at the final visit. Additional endpoints included the proportion of subjects with mild or with moderate renal impairment who achieved a target sUA < 6.0 mg/dL at final visit. Adverse events (AEs) were recorded throughout the study.. Of the 2,269 subjects enrolled, 10.0% were African American and 82.1% were Caucasian. African American subjects were mostly male (89.5%), obese (BMI ≥ 30 kg/m2; 67.1%), with mean baseline sUA of 9.8 mg/dL and mean duration of gout of 10.4 years. The proportions of African American subjects with a baseline history of diabetes, renal impairment, or cardiovascular disease were significantly higher compared to Caucasians (p < 0.001). ULT with febuxostat 80 mg was superior to both febuxostat 40 mg (p < 0.001) and allopurinol (p = 0.004). Febuxostat 40 mg was comparable in efficacy to allopurinol. Significantly more African American subjects with mild or moderate renal impairment achieved sUA < 6.0 mg/dL in the febuxostat 80 group than in either the febuxostat 40 mg or allopurinol group (p < 0.05). Efficacy rates in all treatment groups regardless of renal function were comparable between African American and Caucasian subjects, as were AE rates.. In African American subjects with significant comorbidities, febuxostat 80 mg is significantly more efficacious than either febuxostat 40 mg or allopurinol 200/300 mg. Febuxostat was well tolerated in this African American population.Please see related article: http://www.biomedcentral.com/1741-7015/10/15.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Black or African American; Comorbidity; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Thiazoles; White People; Young Adult

The incidence of gout rises with increasing age. Management of elderly (≥65 years) gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT) in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial.. Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL) gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function) once daily. Flare prophylaxis was provided throughout the study duration.Study endpoints were the percent of elderly subjects with sUA <6.0 mg/dL at the final visit, overall and by renal function status, percent change in sUA from baseline to final visit, flare rates, and rates of adverse events (AEs).. Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0%) than febuxostat 40 mg (61.7%; p < 0.001) or allopurinol (47.3%; p < 0.001) for achieving the primary efficacy endpoint. Febuxostat 40 mg was also superior to allopurinol in this population (p = 0.029). In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028) and febuxostat 80 mg (82.5%; p < 0.001) compared to allopurinol 200/300 mg (46.9%). Compared to allopurinol 200/300 mg, the mean percent change in sUA from baseline was significantly greater for both febuxostat 80 mg (p < 0.001) and febuxostat 40 mg (p = 0.011) groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments.. These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg) in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated.. clinicaltrials.gov NCT#00430248.

Topics: Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

To determine the effects of furosemide on serum urate (SU), plasma oxypurinol and urinary urate.. Twenty-three cases with gout receiving furosemide and allopurinol were recruited. Twenty-three controls with gout receiving allopurinol but no diuretics were matched on age, gender, estimated glomerular filtration rate and allopurinol dose. SU, plasma oxypurinol and urinary urate were assessed on a single occasion. The effects of a single dose of furosemide 40 mg were examined in a separate group of 10 patients receiving allopurinol but not diuretic.. Cases had significantly higher SU and plasma oxypurinol compared with controls despite receiving similar doses of allopurinol. There was no difference in urinary urate excretion. There was a significant increase in area under the curve (AUC)(0-24) for oxypurinol after administration of furosemide 40 mg.. The interaction between allopurinol and furosemide results in increased SU and plasma oxypurinol. The exact mechanisms remain unclear but complex interactions that result in attenuation of the hypouricaemic effects of oxypurinol are likely.. Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, 12609000529246.

Topics: Adult; Aged; Allopurinol; Area Under Curve; Case-Control Studies; Diuretics; Drug Interactions; Drug Therapy, Combination; Female; Furosemide; Gout; Gout Suppressants; Humans; Male; Middle Aged; Oxypurinol; Treatment Outcome; Uric Acid; Urination

To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acid-lowering therapy (ULT).. In total, 241 adult patients with gout, ≥2 gout flares within the past year, and a serum urate level ≥7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16.. More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported ≥1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups.. Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Double-Blind Method; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Placebos; Recombinant Fusion Proteins; Treatment Outcome; Uric Acid

Comprehensive safety evaluation of new drugs for noncardiac indications is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk such as gout. Febuxostat is a potent nonpurine selective inhibitor of xanthine oxidase approved for the treatment of gout. Long-term CV safety of febuxostat is being established in a randomized, allopurinol-controlled clinical study in patients with gout who have increased CV risk using an analytical approach that provides 90% power to meet a noninferiority margin of 1.3 for the hazard ratio (HR) (febuxostat relative to allopurinol). The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina requiring urgent coronary revascularization. Approximately 7,500 men and women with gout and CV disease are being recruited and will be followed up for up to 5 years postrandomization. The statistical plan for the trial uses a design that evaluates the HR of febuxostat to allopurinol based on the primary CV composite end point when there are a maximum of 624 CV events. Interim analyses will be conducted when approximately 25%, 50%, and 75% of events have occurred. At each analysis, if the upper 1-sided confidence limit of the HR is <1.3, the study will be stopped, and the noninferiority of febuxostat relative to allopurinol with regard to CV risk will be declared. The CARES trial will define the CV safety profile of febuxostat and allopurinol in gout patients at high risk for CV events.

Topics: Allopurinol; Cardiovascular Diseases; Double-Blind Method; Febuxostat; Gout; Gout Suppressants; Humans; Prospective Studies; Thiazoles

Streamlining the initiation of allopurinol could result in a cost benefit for a common medical problem and obviate the perception that no treatment is required once acute attacks have resolved. Our objective was to test the hypothesis that there is no difference in patient daily pain or subsequent attacks with early versus delayed initiation of allopurinol for an acute gout attack.. A total of 57 men with crystal-proven gout were randomized to allopurinol 300 mg daily or matching placebo for 10 days. All subjects received indomethacin 50 mg 3 times per day for 10 days, a prophylactic dose of colchicine 0.6 mg 2 times per day for 90 days, and open-label allopurinol starting at day 11. Primary outcome measures were pain on visual analogue scale (VAS) for the primary joint on days 1 to 10 and self-reported flares in any joint through day 30.. On the basis of 51 evaluable subjects (allopurinol in 26, placebo in 25), mean daily VAS pain scores did not differ significantly between study groups at any point between days 1 and 10. Initial VAS pain scores for allopurinol and placebo arms were 6.72 versus 6.28 (P=.37), declining to 0.18 versus 0.27 (P=.54) at day 10, with neither group consistently having more daily pain. Subsequent flares occurred in 2 subjects taking allopurinol and 3 subjects taking placebo (P=.60). Although urate levels decreased rapidly in the allopurinol group (from 7.8 mg/dL at baseline to 5.9 mg/dL at day 3), sedimentation rates and C-reactive protein levels did not differ between groups at any point.. Allopurinol initiation during an acute gout attack caused no significant difference in daily pain, recurrent flares, or inflammatory markers.

Topics: Acute Disease; Allopurinol; Colchicine; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Indomethacin; Male; Pain Management; Pain Measurement; Recurrence; Severity of Illness Index; Treatment Outcome

To determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance-based dose in patients with gout.. Patients with gout who had been receiving a stable dose of allopurinol for ≥ 1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.. Ninety patients were enrolled. The mean age of the patients was 58.7 years (range 27-83 years), 87.9% were male, and 81.9% were of European ancestry. Forty-five patients had a serum urate concentration of ≥ 0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level ≥ 0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/liter (72% versus 88.5%; P = 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.. Increasing the dose of allopurinol above the proposed creatinine clearance-based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Treatment Outcome; Uric Acid

To investigate the pharmacokinetic and pharmacodynamic interaction between probenecid and oxypurinol (the active metabolite of allopurinol) in patients with gout.. This was an open-label observational clinical study. Blood and urine samples were collected to measure oxypurinol and urate concentrations. We examined the effects of adding probenecid to allopurinol therapy upon plasma concentrations and renal clearances of urate and oxypurinol.. Twenty patients taking allopurinol 100-400 mg daily completed the study. Maximum coadministered doses of probenecid were 250 mg/day (n = 1), 500 mg/day (n = 19), 1000 mg/day (n = 7), 1500 mg/day (n = 3), and 2000 mg/day (n = 1). All doses except the 250 mg daily dose were divided and dosing was twice daily. Estimated creatinine clearances ranged from 28 to 113 ml/min. Addition of probenecid 500 mg/day to allopurinol therapy decreased plasma urate concentrations by 25%, from mean 0.37 mmol/l (95% CI 0.33-0.41) to mean 0.28 mmol/l (95% CI 0.24-0.32) (p < 0.001); and increased renal urate clearance by 62%, from mean 6.0 ml/min (95% CI 4.5-7.5) to mean 9.6 ml/min (95% CI 6.9-12.3) (p < 0.001). Average steady-state plasma oxypurinol concentrations decreased by 26%, from mean 11.1 mg/l (95% CI 5.0-17.3) to mean 8.2 mg/l (95% CI 4.0-12.4) (p < 0.001); and renal oxypurinol clearance increased by 24%, from mean 12.7 ml/min (95% CI 9.6-15.8) to mean 16.1 ml/min (95% CI 12.0-20.2) (p < 0.05). The additional hypouricemic effect of probenecid 500 mg/day appeared to be lower in patients with renal impairment.. Coadministration of allopurinol with probenecid had a significantly greater hypouricemic effect than allopurinol alone despite an associated reduction of plasma oxypurinol concentrations. Australian Clinical Trials Registry ACTRN012606000276550.

Topics: Allopurinol; Drug Interactions; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Male; Middle Aged; Oxypurinol; Probenecid; Prospective Studies; Uric Acid; Uricosuric Agents

The Gout Impact Scale (GIS) is a gout-specific quality of life instrument that assesses impact of gout during an attack and impact of overall gout. The GIS has five scales and each is scored from 0 to 100 (worse health). Our objective was to assess minimally important differences (MIDs) for the GIS administered in a randomized controlled trial (RCT) assessing rilonacept vs placebo for prevention of gout flares during initiation of allopurinol therapy.. Trial subjects (n = 83) included those with two or more gout flares (self-reported) in the past year. Of these, 73 had data for Weeks 8 vs 4 and formed the MID analysis group and were analysed irrespective of the treatment assignment. Subjects completed the GIS and seven patient-reported anchors. Subjects with a one-step change (e.g. from very poor to poor) were considered as the MID group for each anchor. The mean change in GIS scores and effect size (ES) was calculated for each anchor's MID group. The average of these created the overall summary MID statistics for each GIS. An ES of 0.2-0.5 was considered to represent MID estimates. Results. Trial subjects (n = 73) were males (96.0%), White (90.4%), with mean age of 50.5 years and serum uric acid of 9.0 mg/dl. The mean change score for the MID improvement group for scales ranged from -5.24 to -7.61 (0-100 scale). The ES for the MID improvement group for the four scales ranged from 0.22 to 0.38.. The MID estimates for GIS scales are between 5 and 8 points (0-100 scale). This information can aid in interpreting the GIS results in future gout RCTs. Trial Registration. Clinicaltrials.gov, www.clinicaltrials.gov, NCT00610363.

Topics: Adult; Age Distribution; Aged; Allopurinol; Follow-Up Studies; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Pain Measurement; Quality of Life; Recombinant Fusion Proteins; Reference Values; Secondary Prevention; Severity of Illness Index; Sex Distribution; Sickness Impact Profile; Single-Blind Method; Treatment Outcome

Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors.. Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28.. Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers.. Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.

Topics: Adult; Aged; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat is potentially a safe and efficacious alternative.. Febuxostat or allopurinol was administered to patients with hyperuricemia including gout for 8 weeks to compare the efficacy and safety of these drugs.. Doses of febuxostat and allopurinol were 10 and 100 mg/d, respectively, during a 12-day introduction period and were increased to 40 and 200 mg/d for the subsequent treatment period of 44 days.. : The percent changes in serum uric acid levels after 8 weeks were -40.75% for the febuxostat group and -34.41% for the allopurinol group (P < 0.001, analysis of variance, closing testing procedure). The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 82.0% for the febuxostat group and 70.0% for the allopurinol group (P = 0.019, logistic regression analysis). Regarding safety, 213 adverse events were observed in the febuxostat group and 220 events in the allopurinol group. For 10 patients (8.2%) in the febuxostat group and 14 patients (11.6%) in the allopurinol group, association with the study drugs could not be ruled out. There were no severe adverse drug reactions in the febuxostat group other than a high frequency of gout attacks induced by the sudden reduction in blood uric acid levels during the early treatment period.. Febuxostat at 40 mg/d demonstrated more potent hypouricemic effects than allopurinol at 200 mg/d, was efficacious regardless of medical history of gout, and is considered safe for treatment of hyperuricemia.

Topics: Administration, Oral; Allopurinol; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

: Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.. : A multicenter study with randomized, placebo-controlled, double-blind, parallel-group comparison was carried out to evaluate the efficacy and safety of febuxostat in 103 patients with hyperuricemia (including patients with gout) in Japan.. : Subjects were treated with febuxostat (20 or 40 mg/d) or a placebo for 8 weeks. The variables evaluated were the percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 8 weeks.. : The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 91.2% in the febuxostat 40-mg/d group, 45.7% in the 20-mg/d group, and 0.0% in the placebo group. The percent changes in serum uric acid levels after 8 weeks were -44.9% in the febuxostat 40-mg/d group, -28.9% in the 20-mg/d group, and -0.6% to -0.5% in the placebo group. No severe or medically significant adverse reaction attributable to febuxostat was noted, and there was no event that could pose a clinical problem. The efficacy did not differ depending on the presence/absence of gout history.. : These results suggest that febuxostat (20 or 40 mg/d) is useful as a new means of treating hyperuricemia and is capable of reducing serum uric acid levels to 6.0 mg/dL or less (goal of treatment) with high safety regardless of the presence/absence of gout history.

Topics: Adult; Central Nervous System Diseases; Dental Enamel; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Japan; Kidney Diseases, Cystic; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.. A multicenter study with randomized, placebo-controlled, double-blind, parallel, intergroup comparison was carried out to evaluate the dose-response relationship, efficacy, and safety of febuxostat in 202 patients with hyperuricemia (including patients with gout) in Japan.. The subjects were treated with febuxostat at fixed maintenance doses (20-80 mg/d) or a placebo for 16 weeks. The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated.. The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8% in the 80-mg/d dose group, 83.3% in the 60-mg/d group, 82.9% in the 40-mg/d group, 46.5% in the 20-mg/d group, and 2.6% in the placebo group (P < 0.001, Mantel-Haenszel test). A statistically significant dose-response relationship was found. The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d. No deaths, events posing a clinical problem, or serious adverse reactions attributable to febuxostat were noted. Similar results were obtained regardless of gout history.. Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80% or more of patients with hyperuricemia (including gout) at doses of 40 mg/d or higher.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.. Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol.. The starting dose of febuxostat and allopurinol was 10 and 100 mg/d, respectively, and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks.. : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96% ± 13.33% and -52.47% ± 9.79% for the febuxostat 40- and 60-mg/d groups, respectively, and -36.55% ± 18.59% for the allopurinol group, indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol (P = 0.0239, 2-sample t test). The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9% and 100% for the febuxostat 40- and 60-mg/d groups, respectively, and 68.8% for the allopurinol group, showing higher achievements for the febuxostat groups compared with the allopurinol group. All adverse drug reactions were mild to moderate in severity, and there were no severe symptoms or reactions leading to drug discontinuation.. These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol.

Topics: Administration, Oral; Allopurinol; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Thiazoles; Time Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

In previous clinical studies of hyperuricemia including gout, although serum uric acid (sUA) levels reduced to 6.0 mg/dL or less in about 80% of patients treated with 40 mg/d febuxostat, a nonpurine selective xanthine oxidase inhibitor, a few patients did not show this result.. The objective of the study was to evaluate the efficacy and safety of long-term febuxostat administration at up to 60 mg/d in patients with hyperuricemia and gout.. In a 52-week, multicenter, open-label trial, febuxostat was initially administered at 10 mg/d; then, the dosage was increased in a stepwise fashion to 40 mg/d. For sUA levels greater than 6.0 mg/dL at week 10, the dosage was increased to 60 mg/d from week 14 onward (60-mg group), but it was maintained at 40 mg/d until the end of the study for patients with sUA levels 6.0 mg/dL or less at week 10 (40-mg group).. The sUA levels in both groups decreased dose dependently. At 52 weeks, 84.5% and 85.0% of the 40- and 60-mg groups, respectively, achieved mean sUA levels 6.0 mg/dL or less. There was no marked difference between the 2 dosage groups in terms of the incidence of adverse events. Furthermore, there were no noteworthy adverse events or adverse drug reactions in the patients with renal dysfunction, and no differences in drug efficacy up to 60 mg/d were noted between the patients with moderate or mild renal dysfunction and those with normal renal function.. Febuxostat seems to be a promising therapeutic drug for gout or hyperuricemia, even in patients with renal dysfunction.

Topics: Administration, Oral; Adult; Dose-Response Relationship, Drug; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Male; Middle Aged; Thiazoles; Time Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need.. To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout.. Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406.. Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group).. Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.. In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008).. Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo.. clinicaltrials.gov Identifier: NCT00325195.

Topics: Allopurinol; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Enzymes, Immobilized; Female; Gout; Gout Suppressants; Humans; Infusions, Intravenous; Male; Middle Aged; Polyethylene Glycols; Treatment Outcome; Urate Oxidase; Uric Acid

Despite an increasing incidence of gout in older age patients with multiple metabolic and cardiovascular comorbidities, there are limited data addressing whether currently available urate-lowering therapy is comparably effective and safe in older (≥65 years of age) versus younger (<65 years of age) patients. In this secondary analysis of data from the CONFIRMS trial, we found that among 374 older subjects, urate-lowering therapy with approved doses of febuxostat or commonly prescribed doses of allopurinol was at least comparable to that in 1894 younger subjects and was well tolerated despite high rates of renal impairment and cardiovascular comorbidities in the older subjects.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Liver Function Tests; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid

The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial.. Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.. Comorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group.. Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable.. NCT00430248.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Dose-Response Relationship, Drug; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperlipidemias; Hypertension; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Obesity; Thiazoles; Treatment Outcome; United States; Uric Acid; Young Adult

Use of urate-lowering therapy (ULT), such as febuxostat or allopurinol, is recommended for the long-term management of hyperuricemia in patients with gout to reduce the incidence of acute flares. Because of the paradoxical relationship between early use of ULT and the increased incidence of gout flares, prophylaxis with either low-dose colchicine or NSAIDs has been recommended, although there have been concerns about the long-term prophylactic use of these agents.. The present analysis examined flare rates during the 3 Phase III trials of febuxostat based on mean postbaseline serum urate (sUA) concentrations and duration of prophylaxis. Adverse events (AEs) were assessed by prophylaxis with colchicine or naproxen.. This investigator-initiated, post hoc reanalysis of data on gout flares from the 3 randomized, placebo-controlled, Phase III trials evaluated the proportion of patients requiring treatment for gout flares at 4-week intervals based on mean postbaseline sUA concentrations <6.0 and ≥ 6.0 mg/dL. The 3 trials enrolled males or females aged 18-85 years who had a diagnosis of gout and a baseline sUA concentration ≥ 8.0 mg/dL. Patients received ULT (febuxostat or allopurinol) or placebo for 6 months or 1 year and flare prophylaxis with colchicine 0.6 mg/d or naproxen 250 mg BID for 8 weeks or 6 months. The prophylactic regimen was chosen at the discretion of the investigator, based on renal function and known intolerance to either drug. Patients with an estimated creatinine clearance <50 mL/min were not to receive naproxen. AEs were summarized based on prophylaxis with colchicine or naproxen.. The 3 trials enrolled a total of 4101 patients with gout. The majority were white (80.1%), male (94.5%), and obese (body mass index ≥ 30 kg/m(2)) (62.8%). The mean duration of gout ranged from 10.9-11.9 years, and the mean baseline sUA concentration ranged from 9.6-9.9 mg/dL. Flare rates increased sharply (up to 40%) at the end of 8 weeks of prophylaxis and then declined gradually, whereas flare rates were consistently low (range, 3%-5%) at the end of 6 months of prophylaxis. Mean postbaseline sUA concentrations were correlated with flare rates; by the end of each study, patients with a mean postbaseline sUA concentration <6.0 mg/dL had fewer flares than did those with a mean postbaseline sUA concentration ≥ 6.0 mg/dL. There were differences in rates of AEs between prophylaxis groups, but the rates did not increase with increased duration of prophylaxis.. This analysis of gout flare data from the 3 Phase III trials of febuxostat found that flare prophylaxis for up to 6 months during the initiation of ULT appeared to provide greater benefit than flare prophylaxis for 8 weeks, with no increase in AEs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Double-Blind Method; Drug Administration Schedule; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Young Adult

To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) < or =0.30 mmol/l (5 mg/dl).. A randomised, controlled, open-label, multicentre trial in gout patients with renal function defined as a calculated creatinine clearance > or =50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr < or =0.30 mmol/l was not attained after 2 months, the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The primary end point was treatment success in either of the two stages, defined as clinical tolerability and attainment of biochemical target sUr.. Sixty-five patients were enrolled in stage 1; 36 received allopurinol and 29 received benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was -0.26 (95% CI from -0.486 to -0.005), p = 0.049. At stage 2, the success rates were 21/27 (78%) and 18/23 (78%), respectively, and the difference was -0.005 (95% CI from -0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions.. Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr < or =0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation.. ISRCTN49563848).

Topics: Aged; Allopurinol; Benzbromarone; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Oxypurinol; Patient Compliance; Prospective Studies; Treatment Outcome; Uric Acid; Uricosuric Agents

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.

Topics: 3T3-L1 Cells; Adiponectin; Adult; Allopurinol; Animals; Benzbromarone; Gene Expression; Gout; Humans; Male; Mice; Middle Aged; PPAR gamma

To establish a benchmark for gout control using the proportion of patients with serum uric acid (SUA) < 0.36 mmol/L, assess patients' understanding of their preventive medication and trial a mail and phone intervention to improve gout control.. Patients clinically diagnosed with gout and baseline SUAs were identified in two South Auckland practices. A mail and phone intervention was introduced aimed at improving the control of gout. Intervention #1 took place in one practice over three months. Intervention #2 occurred in the other practice four to 16 months following baseline.. No significant change in SUA from intervention #1 after three months. The second intervention by mail and phone resulted in improvement in SUA levels with a greater proportion of those with SUA < 0.36 mmol/L and the difference in means statistically significant (p = 0.039 two-tailed paired t-test). Benchmarking for usual care was established at 38-43% SUA < 0.36 level. It was possible to increase from 38% to 50%. Issues relating to gout identified included lack of understanding of the need for long-term allopurinol and diagnosis and management for patients for whom English is not their first language.. 1. Community workers who speak Pacific languages may assist GPs in communicating to non-English speaking patients. 2. Alternative diagnoses should be considered in symptomatic patients with prolonged normouricaemia. 3. GPs should gradually introduce allopurinol after acute gout attacks, emphasising importance of prophylaxis. 4. A campaign to inform patients about benefits of allopurinol should be considered. 5. A simple one keystroke audit is needed for gout audit and benchmarking. 6. GP guidelines for gout diagnosis and management should be available.

Topics: Aged; Allopurinol; Benchmarking; Clinical Audit; Cultural Competency; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Medication Adherence; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Pilot Projects; Uric Acid; White People

To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment.. Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) < or=0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2).. 96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr < or=0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions. 62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p<0.001).. This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr < or =0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.

Topics: Aged; Allopurinol; Benzbromarone; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Probenecid; Prospective Studies; Treatment Failure; Uric Acid

Clinical benefit early in urate-lowering treatment of gout is difficult to document. We examined data from 1,832 gouty subjects treated with either urate-lowering agents or placebo to identify determinants of gout flare incidence and tophus size during year 1 of treatment. Reductions from pretreatment serum urate levels influenced flare frequency and tophus size, but the effect of urate level on flare incidence was biphasic. Lower urate levels were associated with higher flare incidence early in treatment but lower incidence by one year. The complex relationship between urate-lowering and clinical outcome early in treatment has implications for both clinical and investigative approaches to urate-lowering management.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Linear Models; Multivariate Analysis; Odds Ratio; Thiazoles; Time Factors; Treatment Outcome

To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.. Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.. Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.. At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.

Topics: Adult; Aged; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid

Lower dosages of allopurinol are recommended to avoid toxicity in gout patients with impaired renal function. This often has resulted in inadequate control of hyperuricemia. The optimum therapeutic range of plasma oxypurinol concentrations in gout patients with chronic kidney disease has never been investigated. This study was performed to examine the relationships between plasma oxypurinol concentrations and the changes in serum urate level and renal function after taking a standard dose of allopurinol, 300 mg daily, in gout patients with renal insufficiency.. The study was conducted in 27 gout patients with renal insufficiency in a rheumatology clinic at the Rajvithi Hospital, Bangkok. Both new and current patients, after they discontinued allopurinol completely for 4 weeks, were treated with allopurinol 300 mg daily for 6 weeks. Blood samples were collected immediately before and 5 hours after the studied dose had been taken. Serum urate levels and renal function were recorded before and after the 6 weeks of allopurinol treatments.. Most patients receiving allopurinol 300 mg/d had their plasma oxypurinol concentrations higher than the proposed therapeutic range for patients with normal renal function. There were significant relationships between changes in serum urate level with both trough and fifth-hour oxypurinol concentrations (R = 0.42, P = 0.002 and R = 0.27, P = 0.007, respectively). Higher plasma oxypurinol concentrations resulted in a higher percentage of patients who could meet the therapeutic treatment goal. No serious side effect and no significantly change in creatinine clearance were observed indicating that high levels of oxypurinol did not appear to relate to higher prevalence of adverse reaction.. Higher percentages of patients could meet the treatment goal when their plasma oxypurinol concentrations were higher than the proposed therapeutic range for patients with normal renal function.

Topics: Adult; Aged; Allopurinol; Dose-Response Relationship, Drug; Drug Monitoring; Female; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Uric Acid

In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) compared with previous treatment with benzbromarone; and (2) investigate the combination therapy allopurinol-probenecid as an effective alternative treatment compared with previous benzbromarone treatment. A prospective, open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal. Patients were given 200-300 mg allopurinol (stage 1). When allopurinol failed to attain the target serum urate (sUr) levels

Topics: Allopurinol; Benzbromarone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gout; Humans; Hyperuricemia; Male; Middle Aged; Probenecid; Uric Acid; Uricosuric Agents

To observe the curative effect of the self-formulated Jiangzhuo Huoxue Yishen Decoction (JHYD) combined with Western medicine in treatment of gout.. A total of 90 gout patients were randomly assigned to two groups, the control group (45 cases) administrated with Finbid orally in the acute stage and allopurinol in the remission period; and the treatment group (45 cases) treated with the same treatment plus oral administration of JHYD. The therapeutic course for both was 4 weeks. The total curative effect, the effect on main symptoms and on different syndrome types, changes of blood uric acid, adverse reactions and recurrence of gout were observed and compared between the two groups.. The cured and markedly effective rate and the total effective rate in the treatment group were all obviously higher than those in the control group (P<0.05). And the effect was better in the treatment group in decreasing blood uric acid, improving symptoms of main joints and stabilizing the curative effect. The curative effect of the combined therapy on different syndrome types was basically consistent, and it showed few adverse reactions.. The self-formulated JHYD showed synergistic effect with Western medicine in treatment of gout, which could decrease blood uric acid level and improve clinical symptoms.

Topics: Adult; Allopurinol; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Phytotherapy; Treatment Outcome

To evaluate the patterns and determinants of medication use during recurrent gout attacks.. We followed participants with documented gout in an online prospective case-crossover study. During an attack, subjects were asked if they had consulted a physician for the attack and what medications they were using. Definitely inappropriate therapy was defined as use of allopurinol or a uricosuric agent acutely without having used it as a prophylactic. Potentially inappropriate therapy was defined as use of analgesics alone, alternative remedies, or no medications. We estimated the risk of having >or= 1 attack in 1 year using life table methods. We examined the relation of various risk factors to the risk of inappropriate therapy using Poisson regression.. Among 232 participants (mean age 52 yrs, 81% male) with documented gout, the risk of having >or= 1 attack in a year was 69%. One hundred ten participants consulted a physician for each attack, 49 did so for only some attacks, while 43 never consulted a physician for any attack. Fifty-three participants had definitely (n = 10) or potentially (n = 43) inappropriate therapy for their recurrent attacks. Physician consultation for an attack was associated with increased risk of inappropriate therapy (risk ratio, RR, 2.5, p = 0.006), whereas an increasing number of gout attacks was associated with lower risk of inappropriate therapy (RR 0.8, p = 0.01).. Given the high risk of recurrent attacks and the substantial number of persons whose attacks are not appropriately managed, further education about management of gout attacks for both patients and physicians may be warranted.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Cross-Over Studies; Drug Utilization; Female; Gout; Gout Suppressants; Humans; Internet; Male; Medication Errors; Middle Aged; Prospective Studies; Quality Assurance, Health Care; Recurrence; Risk Factors

Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl).. We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.. Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups.. Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Febuxostat; Female; Gout; Humans; Hyperuricemia; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

To assess the efficacy and safety of benzbromarone in patients with renal impairment and severe tophaceous gout (despite receiving optimal conventional therapy).. Six patients with refractory gout (despite optimal therapy) were treated with benzbromarone. Uric acid levels and number of gout attacks were recorded monthly. Adverse events to medications were also recorded.. After 1 year of treatment with benzbromarone, average uric acid level reduced from 0.61 mmol/L to 0.46 mmol/L. Repeated measures tests on the changes in uric acid were clinically significant (p=0.01). The frequency of acute attacks of gout was reduced from 16 (8-20) to 7.3 (1-16); p=0.01. None of the patients reported adverse events with the medications. There were no acute flares resulting from initiation of medications.. Benzbromarone is effective in lowering uric acid levels and in reducing the number of acute attacks of gout in patients who have failed optimal treatment. Making this drug more readily available will increase our therapeutic choices for urate reduction and help decrease the morbidity associated with gout.

Topics: Adult; Allopurinol; Benzbromarone; Creatinine; Female; Gout; Humans; Incidence; Male; Metabolic Clearance Rate; Middle Aged; New Zealand; Treatment Outcome; Uric Acid

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.. We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area.. The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group).. Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups.

Topics: Allopurinol; Double-Blind Method; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Thiazoles; Uric Acid; Xanthine Oxidase

Uric acid is a strong scavenger of reactive oxygen species, which are known to contribute to the development of atherosclerosis, while the incidence of atherosclerotic diseases is rather high in patients with gout. Among the established risk factors for atherosclerosis, oxidized LDL is believed to play a major role in its development and progression. Allopurinol and its active metabolite, oxypurinol, have been suggested to possess an antioxidant ability to scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The objective of this work was to determine the degree of LDL oxidation in gout and the effect of allopurinol on LDL oxidation.. Age-matched male patients with primary intercritical gout and healthy male adults were included in the study. The serum concentrations of oxidized LDL autoantibodies and total antioxidant status were measured using an enzyme immunoassay.. Serum concentrations of oxidized LDL autoantibodies were significantly higher in patients with gout than the control subjects (p < 0.05) and were significantly decreased after allopurinol treatment (p < 0.05), but not by benzbromarone treatment, in spite of the similar concentrations of uric acid and total antioxidant status in serum following their separate administration.. Although the exact mechanism remains unclear, increased serum concentrations of oxidized LDL may play a role in the high incidence of coronary artery disease in gout. In addition, allopurinol may be more preferable to benzbromarone for treatment of gout in light of its inhibitory action toward LDL oxidation.

Topics: Allopurinol; Antioxidants; Autoantibodies; Body Weight; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Gout; Humans; Lipoproteins, LDL; Male; Middle Aged; Smoking; Triglycerides; Uric Acid

The diurnal change of sUA and the effect of febuxostat on this change were investigated in 10 patients with gout and/or hyperuricemia. The diurnal sUA change after the last dose during the 4-week treatment phase (20 mg, QD) was almost the same as the pre-treatment value. Considering the dose, the AUC(obs) and Cmax of unchanged drug in patients with gout and/or hyperuricemia were estimated to be similar to those of healthy male adults. The results show that a 6-week treatment with febuxostat is safe and well-tolerated in the target patient population for this drug.

Topics: Area Under Curve; Enzyme Inhibitors; Febuxostat; Gout; Humans; Hyperuricemia; Male; Oxygen; Thiazoles; Time Factors; Xanthine Dehydrogenase; Xanthine Oxidase

To assess the short-term urate-lowering effect of fenofibrate in men on long-term allopurinol therapy for hyperuricaemia and gout.. Ten male patients (38-74 yr) with a history of chronic tophaceous or recurrent acute gout with hyperuricaemia and on established allopurinol at 300-900 mg/day for > or =3 months were studied in an open-crossover study of fenofibrate therapy. Allopurinol at the established dose was continued throughout the study. Clinical and biochemical assessments (serum urate and creatinine, 24-h urinary excretion of urate and creatinine, liver function tests, creatine kinase and fasting serum lipids) were undertaken at: (i) baseline, (ii) after 3 weeks of once-daily therapy with micronized fenofibrate (Lipantil Micro) at 200 mg and (iii) 3 weeks after fenofibrate was withdrawn.. Fenofibrate was associated with a 19% reduction in serum urate after 3 weeks of treatment (mean+/-S.E. 0.37+/-0.04 vs 0.30+/-0.02 mM/l; P=0.004). The effect was reversed after a 3-week fenofibrate withdrawal period (0.30+/-0.02 vs 0.38+/-0.03 mM/l). There was a rise in uric acid clearance with fenofibrate treatment of 36% (7.2+/-0.9 vs 11.4+/-1.6 ml/min, normal range 6-11; P=0.006) without a significant change in creatinine clearance. Both total cholesterol and serum triglycerides were also reduced. No patient developed acute gout whilst taking fenofibrate.. Fenofibrate has a rapid and reversible urate-lowering effect in patients with hyperuricaemia and gout on established allopurinol prophylaxis. Fenofibrate may be a potential new treatment for hyperuricaemia and the prevention of gout, particularly in patients with coexisting hyperlipidaemia or those resistant to conventional therapy for hyperuricaemia.

Topics: Acute Disease; Adult; Aged; Alkaline Phosphatase; Allopurinol; Arthritis, Gouty; Chronic Disease; Cross-Over Studies; Drug Therapy, Combination; Fenofibrate; Gout; Gout Suppressants; Humans; Hyperuricemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Recurrence; Uric Acid

This study was aimed to evaluate the efficacy of benzbromarone compared to allopurinol in lowering serum uric acid level in hyperuricemic patients with normal renal function (serum creatinine < or = 1.5). The authors conducted a crossover study consisting of two four-week treatment periods of allopurinol 300 mg/day and benzbromarone 100 mg/day separated by a four-week washout period. Fourteen patients with mean age and duration of hyperuricemia of 60.78 +/- 8.62 and 6.93 +/- 3.69 years, respectively, were recruited and all completed our study protocol. This study was a crossover design consisting of two four-week treatments of allopurinol and benzbromarone separated by a four-week washout period. The serum uric acid level was reduced from 9.89 +/- 1.43 mg/dl to 5.52 +/- 0.83 mg/dl and from 9.53 +/- 1.48 to 4.05 +/- 0.87 mg/dl by allopurinol and benzbromarone, respectively. The efficacy of benzbromarone in lowering serum uric acid level was significantly superior to allopurinol (p=0.005). No patient reported clinical side effects during treatment with either drug. In conclusion, the authors have shown that benzbromarone is more effective than allopurinol in the reduction of serum uric acid levels in hyperuricemic patients with normal renal function.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gout; Humans; Male; Middle Aged; Probability; Statistics, Nonparametric; Treatment Outcome; Uric Acid; Uricosuric Agents; Urinalysis

The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout.. Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination.. Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction.. Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Crystallization; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies; Uric Acid

To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout.. A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals.. There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine.. A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.

Topics: Allopurinol; Chronic Disease; Colchicine; Crystallization; Extracellular Space; Follow-Up Studies; Gout; Gout Suppressants; Humans; Knee Joint; Male; Prospective Studies; Treatment Outcome; Uric Acid

To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms.. Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period.. 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function.. Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.

Topics: Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Benzbromarone; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Risk Factors; Uric Acid; Uricosuric Agents

The uric acid concentration in blood has been widely accepted as a diagnostic indicator of hyperuricemia and gout, and its assay method is well established. In the present study, we developed a simple and rapid method for the determination of uric acid in hair, which can be obtained non-invasively. The concentration (nmol/mg hair) of uric acid extracted from 10-20 mg hair with 0.1 M potassium hydroxide was determined by an enzymatic method using uricase. The concentration of uric acid (nmol/mg hair, mean+/-S.D.: 0.49+/-0.157, n=16) in hair from hyperuricemic patients was significantly higher than that (0.26+/-0.107, n=8) in healthy volunteers (p<0.01). The within-run and between-day precision (CVs) of the assay was 9.6-10.3% (n=10 each) and 11.6-16.3% (n=7 each), respectively. The concentration (nmol/mg hair, y) of uric acid in hair correlated well with that in serum (mg/l, x): y=0.09x-0.12 (r=0.75, Syx=0.122, n=23). Changes in the concentration of uric acid in the hair of antihyperuricemic drug-treated patient paralleled that in serum, suggesting that the concentration of uric acid in hair is a reliable indicator of the metabolic control in hyperuricemia.

Topics: Adult; Allopurinol; Gout; Gout Suppressants; Hair; Humans; Hydroxides; Middle Aged; Potassium Compounds; Uric Acid

To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.. Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).. Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal function improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.. Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Chronic Disease; Drug Administration Schedule; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Drug Interactions; Gout; Gout Suppressants; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid

To investigate whether allopurinol and benzbromarone affect the concentration of uridine in plasma, allopurinol or benzbromarone were administered to patients with gout for 3 to 6 months. Allopurinol decreased the concentrations of uridine and uric acid in plasma and the urinary excretion of uric acid, but increased the plasma concentration and urinary excretion of oxypurines and orotidine. Benzbromarone decreased the concentration of uric acid in plasma and increased the excretion of uric acid in urine. However, it did not affect the plasma concentration of uridine or oxypurines or the urinary excretion of oxypurines or orotidine. These results suggest that orotidilytic decarboxylase was inhibited by allopurinol and oxypurinol ribonucleotides and/or that phosphoribosyl pyrophosphate (PRPP) was consumed by conversion from hypoxanthine, allopurinol, and oxypurinol to the respective ribonucleotides, resulting in a decrease in the de novo synthesis of pyrimidine leading to the decreased concentration of uridine in plasma. Furthermore, it was suggested that benzbromarone did not affect the de novo synthesis of pyrimidine or purine.

Topics: Adult; Allopurinol; Benzbromarone; Dose-Response Relationship, Drug; Gout; Gout Suppressants; Humans; Male; Middle Aged; Purines; Pyrimidines; Time Factors; Uric Acid; Uricosuric Agents; Uridine; Xanthine Oxidase

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Allopurinol; Benzbromarone; Chromatography, Ion Exchange; Drug Therapy, Combination; Gout; Humans; Isoelectric Focusing; Male; Middle Aged; Oxypurinol; Probenecid; Radioimmunoassay; Transferrin

Nonsteroidal anti-inflammatory drugs (NSAIDs) are now commonly used for the treatment of acute gout, but caution is required in view of their adverse effects, especially in the elderly. Colchicine is still an effective acute agent, but care must be taken to monitor toxicity. Intra-articular glucocorticosteroid therapy is useful and very safe; oral steroids and corticotrophin (adrenocorticotrophic hormone) may have a small role in acute therapy and seem safe when used over short time spans. Low dose colchicine may have a cost and toxicity advantage over NSAIDs in the prophylaxis of gout when commencing therapy aimed at reducing elevated plasma urate concentrations. Allopurinol is more frequently used than uricosuric agents such as probenecid, and toxicity may be largely avoided by tailoring dosage schedules according to renal function.

Topics: Adrenocorticotropic Hormone; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Double-Blind Method; Glucocorticoids; Gout; Gout Suppressants; Humans; Probenecid; Sulfinpyrazone

The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout. We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim (2 x 100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron (2 tablets) or Zyloprim (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days. On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14. Benzbromarone lowered plasma oxypurinol concentrations (Allomaron/Zyloprim mean ratio of AUC0-->24 was 59%; 95% confidence interval 54-64%), but did not affect plasma allopurinol concentrations. Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Gout; Humans; Male; Middle Aged; Oxypurinol; Uric Acid

In an open-controlled, randomized trial over 24 weeks, the serum uric acid lowering effect of a daily dose of 100 mg allopurinol in combination with 20 mg benzbromarone compared to 300 mg allopurinol only was investigated on a total of 60 patients suffering from hyperuricemia. Both preparations led to a decrease of the serum uric acid value to normal. In those patients however, who had received the combination the reduction of the serum uric acid level was more pronounced. Tolerance was generally good. Side-effects were not reported.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Dose-Response Relationship, Drug; Drug Combinations; Female; Gout; Humans; Kidney Calculi; Male; Middle Aged; Uric Acid

Fifty patients with gout were randomly allocated to one of 2 groups receiving allopurinol, either continuously or for 2 months every year. Patients with renal functional impairment or tophacous gout were excluded. Duration of treatment ranged from 2-4 years. Acute gouty arthritis occurred to a similar degree in the 2 groups during the first year, but thereafter attacks occurred with diminishing frequency in the continuous group compared with the intermittent group. We concluded that the intermittent administration of allopurinol as given here is less effective in controlling symptoms of gout than continuous therapy.

Topics: Allopurinol; Drug Administration Schedule; Gout; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Time Factors; Uric Acid

Topics: Allopurinol; Clinical Trials as Topic; Drug Evaluation; Gout; Humans; Kidney Diseases; Kidney Tubules; Male; Uric Acid

This study compared the effects of azapropazone and indomethacin plus allopurinol in the management of acute gout and hyperuricaemia. A group of 93 patients predominantly based in general practice were randomly allocated to the two treatment regimens (azapropazone (days 1-225) or indomethacin (1-28) followed by allopurinol (29-225)) on a double-blind double dummy basis. Azapropazone produced a substantial reduction in serum uric acid levels by day 4 compared with day 1 (P<0.002) and was superior to indomethacin with regard to recorded levels of serum uric acid at day 4 (P<0.01) and day 28 (P<0.05). From day 28 onwards allopurinol produced and azapropazone maintained similar reductions in serum uric acid. Both treatments rapidly controlled the initial acute attacks of gout and both produced side effects similar in frequency and nature. Fewer breakthrough attacks of gout occurred in the azapropazone group (12) than the indomethacin/allopurinol group (21).Although the results achieved in both treatment groups were similar it has been shown that azapropazone is effective monotherapy for controlling both acute attacks of gout and hyperuricaemia.

Topics: Adult; Aged; Allopurinol; Apazone; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Gout; Humans; Indomethacin; Male; Middle Aged; Random Allocation; Triazines; Uric Acid

The antihyperuricemic properties of amflutizole were investigated in studies designed to determine its efficacy and mechanisms of action in individuals with gout and hyperuricemia. In a randomized double blind, multiple dose, crossover study of 29 patients, amflutizole caused a significant dose dependent reduction in serum urate concentrations. Mean serum urate concentrations decreased significantly from 9.6 +/- 1.5 mg/dl to 7.2 +/- 1.3 mg/dl with the 500 mg dosage (p less than 0.01). Detailed studies in 5 patients demonstrated evidence for modest xanthine oxidase inhibition. However, the majority of the antihyperuricemic effect was derived from an enhanced renal clearance of uric acid. Although the drug has significant antihyperuricemic properties, these were inadequate to achieve adequate control of the serum urate concentration in hyperuricemia and gout at the doses utilized.

Topics: Adult; Aged; Arthritis; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Tolerance; Female; Gout; Gout Suppressants; Humans; Kidney; Male; Middle Aged; Random Allocation; Thiazoles; Uric Acid; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Benzbromarone; Benzofurans; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gout; Humans; Male; Metabolic Clearance Rate; Middle Aged; Oxypurinol; Purines; Pyrimidines

Fifty-nine patients with primary gout were treated with either a combination of colchicine and allopurinol or colchicine alone. Assessments of renal function over 2 years revealed a statistically significant fall of glomerular filtration rate an urine concentrating ability in those receiving only colchicine. The renal function of patients given allopurinol did not change. Treatment with allopurinol resulted ina significant reduction of ammonium excretion, a phenomenon which could not be readily explained. Urate clearance also declined during allopurinol treatment, and the impaired urate clearance associated with gout became more evident. The most important observation was that allopurinol retarded an apparent decline of renal function. Presumably this was achieved through its hypouricaemic effect and implies that the hyperuricaemia of gouty patients is deleterious to the kidneys.

Topics: Adult; Allopurinol; Clinical Trials as Topic; Colchicine; Drug Therapy, Combination; Female; Gout; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Random Allocation

Topics: Allopurinol; Benzbromarone; Benzofurans; Clinical Trials as Topic; Gout; Humans; Uric Acid

Topics: Adult; Aged; Allopurinol; Apazone; Female; Gout; Humans; Kidney Function Tests; Male; Middle Aged; Triazines; Uric Acid

Topics: Adult; Aged; Allopurinol; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Gout; Humans; Middle Aged; Time Factors; Uric Acid

The efficacy of a retard preparation of allopurinol is verified by biochemical, pharmacological and clinical investigations. The action of a 300 mg allopurinol tablet, with normal release and absorption parameters, is based on the specific activity of oxypurinol, a metabolite which is formed from allopurinol according to a biotransformation process. The inhibitory action of oxypurinol on xanthine oxidase amounts to only 1/5th of that of allopurinol. On the other hand allopurinol shows an extremely short half life, so that a slow-release preparation of allopurinol seems the better way of administration to get adequate uricostatic efficacy by a single dose over a 24-hour period.

Topics: Allopurinol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Gout; Humans; Uric Acid

Topics: Allopurinol; Clinical Trials as Topic; Colchicine; Female; Follow-Up Studies; Gout; Humans; Kidney; Kidney Calculi; Male; Middle Aged; Uric Acid

12 hyperuremic male patients got during two comparative tests for 16 days 300 mg/die Allopurinol or 100 mg/die Benzbromarone or a combination of 100 mg Allopurinol with 20 mg Benzbromarone. During this time the renal elimination of uric acid, sodium, calcium, magnesium and citrate war measured and the renal clearance of uric acid, creatinine and sodium was determinated. Without any therapy the combination of 100 mg Allopurinol with 20 mg Benzbromarone per die reduces the elimination of uric acid significantly under the original value in the 24-hour-urine. The elimination of the uric acid increases with 300 mg/die Allopurinol. The clearance ratio of uric acid and creatinine rises 33% to 60%. With 100 mg/die Benzbromarone this value goes up to 233% compared with the results without therapy. At the same time the therapy with Brenzbromarone makes the clearance ratio of uric acid to sodium rise significantly to 257%. Under the 3 types of therapy there is no significant change in the 24-hours-urine of the clearance of creatinine and sodium, the clearance ratio of sodium to creatinine and the elimination ratio of sodium, calcium, magnesium and citrate. Hyperuremic patients with urolithic diathesis need Allopurinol therapy without any combination.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Benzofurans; Calcium; Citrates; Creatinine; Glomerular Filtration Rate; Gout; Humans; Magnesium; Male; Middle Aged; Natriuresis; Sodium; Uric Acid

Topics: Adult; Allopurinol; Benzbromarone; Benzofurans; Clinical Trials as Topic; Drug Combinations; Female; Gout; Humans; Male; Metabolic Clearance Rate; Middle Aged; Uric Acid

Allopurinol was administered to seven patients with gout to compare the effects of three different methods of administration. Allopurinol 100 mg given three times daily. Allopurinol given once daily as three 100 mg tablets. Allopurinol given once daily as a single 300 mg tablet. Allopurinol as a single dose in the morning gave as sustained control of plasma levels as did divided administration.

Topics: Administration, Oral; Adult; Aged; Allopurinol; Clinical Trials as Topic; Gout; Humans; Middle Aged; Tablets; Time Factors; Uric Acid

The effect of daily administration of a single 300-mg tablet of allopurinol on serum urate levels was compared with the effect of divided doses of the drug (100 mg three times a day) in an open-labeled crossover trial of 20 patients with hyperuricemia and gout. Under both regimens of treatment there was a prompt fall in serum urate levels, and analysis of variance indicated no significant difference between the two modes of administration of allopurinol. Nor was there any significant difference in the minimum serum levels of oxypurinol. On the basis of this short-term study, the use of a single 300-mg tablet of allopurinol per day appears to be an effective means of lowering the elevated serum urate levels of individuals with gouty hyperuricemia and compares favorably with the results obtained by allopurinol in divided doses.

Topics: Acute Disease; Adult; Aged; Allopurinol; Analysis of Variance; Chemical Phenomena; Chemistry; Gout; Humans; Informed Consent; Male; Methods; Middle Aged; Pyrazoles; Pyrimidines; Spectrophotometry; Tablets; Time Factors; Uric Acid

Topics: Adult; Allopurinol; Blood Pressure; Creatinine; Female; Follow-Up Studies; Glomerular Filtration Rate; Gout; Humans; Hypertension; Male; Mathematics; Middle Aged; Placebos; Uric Acid

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Benzofurans; Clinical Trials as Topic; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Metabolic Clearance Rate; Middle Aged; Urea; Uric Acid

Topics: Adult; Aged; Allopurinol; Clinical Trials as Topic; Drug Tolerance; Evaluation Studies as Topic; Gout; Humans; Middle Aged; Tablets; Time Factors

Topics: Allopurinol; Arthritis, Rheumatoid; Azathioprine; Blood Cells; Capsules; Clinical Trials as Topic; Eye Diseases; Female; Gastrointestinal Diseases; Gout; Humans; Indomethacin; Lupus Erythematosus, Systemic; Male; Middle Aged; Rheumatic Diseases; Scleroderma, Systemic; Spondylitis, Ankylosing; Suppositories

Topics: Administration, Oral; Adolescent; Adult; Alkaline Phosphatase; Allopurinol; Blood Urea Nitrogen; Child; Child, Preschool; Clinical Trials as Topic; Female; Gout; Humans; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Uric Acid

Topics: Aged; Allopurinol; Ammonia; Ammonium Chloride; Clinical Trials as Topic; Computers; Female; Gout; Humans; Male; Middle Aged; Uric Acid

Topics: Allopurinol; Clinical Trials as Topic; Gout; Humans; Male; Middle Aged

Topics: Adult; Allopurinol; Clinical Trials as Topic; Gout; Humans; Kidney Tubules; Metabolic Clearance Rate; Middle Aged; Pyrazinamide; RNA; Uric Acid

The effect of various drugs on urate binding to plasma proteins was investigated in normal subjects. Whereas allopurinol, aspirin, phenylbutazone, probenecid, and sulphinpyrazone all significantly reduced plasma urate concentrations, only aspirin, phenylbutazone, and probenecid significantly impaired urate binding. Colchicine and indomethacin in the doses administered had no significant effect on plasma urate concentrations or binding. In the case of aspirin, urate binding was reduced to 25% of normal, and this effect was quickly abolished after cessation of therapy. Phenylbutazone reduced urate binding to 56% and probenecid to 46% of normal; this impairment was still detected four days after cessation of therapy. Drugs may impair urate binding by competition for plasma protein binding sites, with displacement of bound urate. Impairment of urate binding in vivo by administration of certain drugs may be relevant to the precipitation of acute gouty arthritis, to the formation of gouty tophi, and to the augmentation of uricosuria. Furthermore, the role of drugs must be seriously considered during all studies on urate binding in patients with gout.

Topics: Adult; Allopurinol; Arthritis; Aspirin; Blood Proteins; Chromatography, DEAE-Cellulose; Colchicine; Female; Gout; Humans; Indomethacin; Male; Phenylbutazone; Probenecid; Protein Binding; Sulfinpyrazone; Uric Acid

Topics: Allopurinol; Enzyme Therapy; Gout; Humans; Kidney Calculi; Uric Acid; Urinary Calculi; Xanthine Oxidase

Topics: Allopurinol; Clinical Trials as Topic; Colchicine; Enzyme Therapy; Follow-Up Studies; Gout; Humans; Liver Function Tests; Male; Probenecid; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Clinical Trials as Topic; Colchicine; Diuresis; Enzymes; Gout; Humans; Purines; Uric Acid; Xanthine Oxidase

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Arthritis, Rheumatoid; Clinical Trials as Topic; Duodenal Ulcer; Enzyme Therapy; Female; Gout; Humans; Male; Middle Aged; Psoriasis; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

Topics: Adult; Aged; Enzyme Therapy; Enzymes; Female; Gout; Humans; Liver Function Tests; Male; Middle Aged; Proteinuria; Radiography; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Clinical Trials as Topic; Enzyme Therapy; Female; Gout; Humans; Male; Sulfinpyrazone; Xanthine Oxidase

Topics: Clinical Trials as Topic; Enzyme Therapy; Gout; Humans; Xanthine Oxidase

Topics: Clinical Trials as Topic; Enzyme Therapy; Gout; Humans; Xanthine Oxidase

This study aimed to develop and evaluate an allopurinol adherence tool based on steady-state oxypurinol plasma concentrations, allopurinol's active metabolite.. Plasma oxypurinol concentrations were simulated stochastically from an oxypurinol pharmacokinetic model for allopurinol doses of 100-800 mg daily, accounting for differences in renal function, diuretic use and ethnicity. For each scenario, the 20th percentile for peak and trough concentrations defined the adherence threshold, below which imperfect adherence was assumed. Predictive performance was evaluated using both simulated low adherence and against data from 146 individuals with paired oxypurinol plasma concentrations and adherence measures. Sensitivity and specificity (S&S), negative and positive predictive values (NPV, PPV) and receiver operating characteristic (ROC) area under the curve (AUC) were determined. The predictive performance of the tool was evaluated using adherence data from an external study (CKD-FIX).. The allopurinol adherence tool produced S&S values for trough thresholds of 89-98% and 76-84%, respectively, and 90%-98% and 76-83% for peak thresholds. PPV and NPV were 79-84% and 88-94%, respectively, for trough and 80-85% and 89-98%, respectively, for peak concentrations. The ROC AUC values ranged from 0.84 to 0.88 and from 0.86 to 0.89 for trough and peak concentrations, respectively. S&S values for the external evaluation were found to be 75.8% and 86.5%, respectively, producing an ROC AUC of 0.8113.. A tool to identify people with gout who require additional support to maintain adherence using plasma oxypurinol concentrations was developed and evaluated. The predictive performance of the tool is suitable for adherence screening in clinical trials and may have utility in some clinical practice settings.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Oxypurinol; Tool Use Behavior

The American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target approach to lower serum urate (SU). Using the ACR's Rheumatology Informatics System for Effectiveness registry, we examined the use of a treat-to-target approach among gout patients receiving long-term urate-lowering therapy (ULT) and followed longitudinally by rheumatologists.. Included patients had one or more diagnoses for gout in 2018-2019 and continuous use of ULT for ≥12 months. We assessed the proportions of patients with SU monitoring and, among those tested, who achieved SU <6.0 mg/dl during the measurement year. Multilevel logistic regression adjusting for sociodemographics, comorbidities, region, and health care utilization was used to determine factors associated with SU monitoring and achievement of target SU.. A total of 9,560 were included. The mean ± SD age was 67.2 ± 12.7 years, 73.5% of patients were male, and 32.3% were non-White. Fifty-six percent of patients had at least 1 SU recorded during the measurement year; among patients with at least 1 SU recorded, 74% achieved the SU target. In multivariate analyses, non-White patients were slightly less likely to be tested or achieve a target SU.. Among gout patients receiving long-term ULT followed longitudinally by rheumatologists, more than half had a documented SU, and among those tested, three-quarters achieved the recommended SU target. Routine monitoring of SU is a first step toward improving quality of care for patients with gout.

Topics: Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Registries; Rheumatology; United States; Uric Acid

Lesinurad and allopurinol have been formulated in a combined dosage form providing a new challenge for the treatment of gout attacks. Two mathematical based spectrophotometric methods, area under the curve, and artificial neural networks have been developed for simultaneous determination of lesinurad and allopurinol in pure form and in combined pharmaceutical dosage form. Area under the curve has been utilized to resolve the spectral overlap between lesinurad and allopurinol. Values of area under the curve and area absorptivity were measured at two selected wavelength ranges of 242-250 nm and 255-265 nm. Two mathematically constructed equations have been used to determine the concentrations of the drugs under the study. Advanced chemometry based model, artificial neural network, has been developed utilizing the UV spectral data of lesinurad and allopurinol through various defined steps. A five-level, two-factor experimental design was used to construct 25 mixtures. Thirteen mixtures were used to set up the calibration model and 12 mixtures were used to construct a validation set. The artificial neural network model was optimized to enable precise spectrophotometric determination of the drugs under the study. The described mathematically bases spectrophotometric methods have been successfully applied to the determination of lesinurad and allopurinol in the new combined, Duzallo® tablets. Furthermore, the greenness of the described methods was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The proposed methods showed more adherence to the greenness characters in comparison to the previously reported HPLC method.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Triazoles

To understand the clinical variables that contribute to the patient and physician assessments of gout control and which variables predict discordant assessments.. Patients (n = 223) with gout taking allopurinol ≥300 mg daily attended a standardized gout assessment visit. Participants and physicians completed questionnaires rating their assessment of current gout control using a numerical rating scale (0 = not at all controlled, 10 = fully controlled). Discordance between patients' and physicians' scores was defined as an absolute difference of >2 units.. The mean ± SD patient gout control score was 8.09 ± 2.24, and the physician gout control score was 7.38 ± 2.63 (P < 0.001 for comparison). Absence of gout flares in the last 12 months and in the last 3 months and serum urate at the treatment target (<6 mg/dl) were associated with higher patient and physician gout control scores. Absence of tophus also predicted higher physician, but not patient, gout control scores. Discordant scores for gout control were present in 50 participants (22.3%), mostly due to lower assessment of disease control by physicians. Gout flare in the preceding 3 months (odds ratio [OR] 5.9, P < 0.001) and tophus (OR 3.1, P = 0.007) predicted discordant disease-control assessments in which physicians scored lower gout control than patients.. For both patients and physicians, absence of gout flares and serum urate levels at the treatment target predict assessment of gout control. However, discordance between patients and physicians in their assessment of disease control is not uncommon, with recent gout flares and tophus predicting lower scores by physicians than patients.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Symptom Flare Up; Uric Acid

This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016.. Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013-2015 versus 2016-2018 were compared regarding persistence and compliance with treat-to-target principles.. The incidence of gout was 221-247 per 100 000 person-years during 2014-2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016-2018 compared with 2013-2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 µmol/L (45% vs 30%, p < 0.001).. Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014-2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Sweden; Treatment Outcome; Uric Acid

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Secondary Prevention; Treatment Outcome

In the present study, we aimed to investigate the association between urate-lowering drugs and cardiovascular events, primarily focusing on the risk of febuxostat and topiroxostat when compared with allopurinol in Japan. We conducted an observational study with a cohort design using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, including new urate-lowering drugs users between August 1, 2010, and March 31, 2018. Exposure and control groups were defined based on the first prescription of urate-lowering drugs as follows: febuxostat or topiroxostat for exposure groups, allopurinol for the control group, and benzbromarone for the secondary control group. The primary outcome was cardiovascular events, defined as a composite of acute coronary syndrome, cerebral infarction, and cerebral hemorrhage. Hazard ratios were estimated using a Cox proportional hazards model. The number of patients in each exposure and control group was 1,357,671 in the febuxostat group, 83,683 in the topiroxostat group, 1,273,211 in the allopurinol group, and 258,786 in the benzbromarone group. The adjusted hazard ratios for the cardiovascular risk were 0.97 (95% confidence interval [CI]: 0.95-0.98) for febuxostat and 0.84 (95% CI: 0.78-0.90) for topiroxostat groups. The benzbromarone group exhibited similar results. No increased cardiovascular risk was observed with febuxostat or topiroxostat when compared with allopurinol in patients with hyperuricemia in Japan. These results provide real-world evidence regarding the cardiovascular risk associated with urate-lowering drugs, indicating that no additional safety-related regulatory actions are warranted in Japan.

Topics: Allopurinol; Benzbromarone; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Insurance, Health; Japan; Risk Factors; Treatment Outcome; Uric Acid

The occurrence of gout attacks at the start of uric acid lowering treatment worsens compliance. We aimed to determine the appropriate dose of febuxostat to reduce the occurrence of gout attacks during the initial treatment period.. We retrospectively analyzed the data of patients diagnosed with gout who underwent treatment at Jeju National University Hospital between May 2018 and May 2020.. Two-hundred and twenty-seven patients were included, with a mean age of 53.2 ± 16.4 years, and 219 (96.5%) were male. The patients were divided into two groups according to the starting dose of febuxostat (20 mg vs. 40 mg). There were no significant differences in mean age, disease duration, colchicine, estimated glomerular filtration rate (eGFR), initial uric acid levels, and presence of subcutaneous tophi between the two groups. Gout attacks occurred more frequently in the 20 mg group than in the 40 mg group during the first 3 months of treatment (32.0% vs. 14.3%, p = 0.002), particularly during the first month (21.3% vs. 7.5%, p = 0.005). Multivariate logistic regression analysis was conducted adjusting for the effects of disease duration, the presence of subcutaneous tophi, eGFR, and initial uric acid levels. A febuxostat starting dose of 40 mg (odds ratio, 0.464; 95% confidence interval [CI], 0.246 to 0.862; p = 0.015) and anti-inflammatory prophylaxis (odds ratio, 0.359; 95% CI, 0.158 to 0.813; p = 0.014) were found to be independent factors associated with a gout attack.. Starting uric acid lowering treatment with febuxostat 40 mg rather than 20 mg may reduce the incidence of gout attacks in the early period of treatment in Korean patients with gout.

Topics: Adult; Aged; Allopurinol; Arthritis, Gouty; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Uric Acid

Febuxostat is the drug used to treat hyperuricemia in patients with gout. Recently, the usage of Febuxostat has been controversial over the side effects in cardiovascular. The study aimed to comparatively analyze the risk of cardiovascular disease associated with febuxostat and allopurinol use in Korean patients with gout. A cohort study was conducted using national insurance claim data from the Health Insurance Review and Assessment Service (HIRA). Adult patients who were diagnosed with gout and prescribed febuxostat or allopurinol more than once from July 1, 2015, to June 30, 2018 were studied. The outcome was cardiovascular disease. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to estimate the hazard ratio with a 95% confidence interval. In total, 90,590 patients were defined as the final study cohort who had an average follow-up of 467 days, including 28,732 and 61,858 patients in the febuxostat and allopurinol groups, respectively. After the 1:1 propensity score matching, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.17; 95% CI: 1.10-1.24). In the sensitivity analysis, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.09; 95% CI: 1.04-1.15). However, further sensitivity analysis showed no statistically significant difference between the febuxostat group and allopurinol group after adjusting for cardiovascular disease history before the index date. Similarly, no statistically significant difference was found between the two drugs in the subgroup analysis. Febuxostat was not associated with a significantly increased risk of cardiovascular disease.

Topics: Allopurinol; Cardiovascular Diseases; Cohort Studies; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Republic of Korea; Retrospective Studies

The genetic determinants of the allopurinol dose-concentration relationship have not been extensively studied. We aimed to clarify what factors, including genetic variation in urate transporters, influence oxypurinol pharmacokinetics (PKs). A population PK model for oxypurinol was developed with NONMEM (version 7.3). The influence of urate transporter genetic variants for ABCG2 (rs2231142 and rs10011796), SLC2A9/GLUT9 (rs11942223), SLC17A1/NPT1 (rs1183201), SLC22A12/URAT1 (rs3825018), SLC22A11/OAT4 (rs17300741), and ABCC4/MRP4 (rs4148500), as well as other participant factors on oxypurinol PKs was assessed. Data from 325 people with gout were available. The presence of the T allele for ABCG2 (rs2231142) and SLC17A1/NPT1 (rs1183201) was associated with a 24% and 22% increase in oxypurinol clearance, respectively, in univariate analysis. This effect was not significant in the multivariate analysis. In the final model, oxypurinol PKs were predicted by creatinine clearance, diuretic use, ethnicity, and body weight. We have found that genetic variability in the transporters examined does not appear to influence oxypurinol PKs.

Topics: Allopurinol; Glucose Transport Proteins, Facilitative; Gout; Humans; Organic Anion Transporters; Organic Cation Transport Proteins; Oxypurinol; Uric Acid

In gout, hyperuricemia promotes urate crystal deposition, which stimulates the NLRP3 inflammasome and interleukin-1β (IL-1β)-mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia-independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis in a young female patient with normouricemia diagnosed as having sufficient and weighted classification criteria for gout according to the American College of Rheumatology (ACR)/EULAR gout classification criteria (the proband).. We conducted whole-genome sequencing, quantitative proteomics, whole-blood RNA-sequencing analysis using serum samples from the proband. We used a mouse model of IL-1β-induced knee synovitis to characterize proband candidate genes, biomarkers, and pathogenic mechanisms of gout.. Lubricin level was attenuated in human proband serum and associated with elevated acute-phase reactants and inflammatory whole-blood transcripts and transcriptional pathways. The proband had predicted damaging gene variants of NLRP3 and of inter-α trypsin inhibitor heavy chain 3, an inhibitor of lubricin-degrading cathepsin G. Changes in the proband's serum protein interactome network supported enhanced lubricin degradation, with cathepsin G activity increased relative to its inhibitors, SERPINB6 and thrombospondin 1. Activation of Toll-like receptor 2 (TLR-2) suppressed levels of lubricin mRNA and lubricin release in cultured human synovial fibroblasts (P < 0.01). Lubricin blunted urate crystal precipitation and IL-1β induction of xanthine oxidase and urate in cultured macrophages (P < 0.001). In lubricin-deficient mice, injection of IL-1β in knees increased xanthine oxidase-positive synovial resident M1 macrophages (P < 0.05).. Our findings linked normouricemic erosive gout to attenuated lubricin, with impaired control of cathepsin G activity, compounded by deleterious NLRP3 variants. Lubricin suppressed monosodium urate crystallization and blunted IL-1β-induced increases in xanthine oxidase and urate in macrophages. The collective activities of articular lubricin that could limit incident and erosive gouty arthritis independently of hyperuricemia are subject to disruption by inflammation, activated cathepsin G, and synovial fibroblast TLR-2 signaling.

Topics: Animals; Arthritis, Gouty; Cathepsin G; Female; Gout; Humans; Hyperuricemia; Inflammation; Interleukin-1beta; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Toll-Like Receptor 2; Uric Acid; Xanthine Oxidase

Topics: Animals; Chalcone; Chalcones; Enzyme Inhibitors; Gout; Hyperuricemia; Rats; Structure-Activity Relationship; Uric Acid; Xanthine Oxidase

The gouty tophus is an organized structure composed of monosodium urate (MSU) crystals and chronic inflammatory soft tissue. This dual-energy computed tomography (DECT) study aimed to determine whether the composition of the tophus changes during urate-lowering therapy.. Serial DECT scans from 32 people with gout were obtained over 2 years of allopurinol therapy, dose-escalated to serum urate of <0.36 mmoles/liter. Up to 5 index tophi were selected for each patient, with 103 separate tophi included in the analysis. Using manual outlining methods of conventional CT and DECT scans, the same index tophi were serially measured for total tophus volume and urate volume. For each tophus, the soft tissue volume was then calculated by subtracting the urate volume from the total tophus volume.. The mean ± SD serum urate reduced from 0.43 ± 0.03 mmoles/liter at baseline to 0.31 ± 0.02 mmoles/liter at year 2. The mean ± SD total tophus volume reduced over the 2-year period from 5.17 ± 5.55 cm. The composition of the tophus is dynamic and changes during urate-lowering therapy for gout management. The soft tissue component of the tophus is slower to respond and may persist without measurable MSU crystal deposition.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Tomography, X-Ray Computed; Uric Acid

Poor adherence to allopurinol among people with gout contributes to suboptimal gout management. This study sought to understand the facilitators and barriers to allopurinol adherence across the three stages of medication adherence, and patient perspectives on strategies to improve adherence, including self-monitoring urate concentration.. Semi-structured interviews were conducted with 26 people with gout, previously or currently taking allopurinol. De-identified verbatim transcripts were thematically analysed using an inductive and deductive approach.. Facilitators of adherence during allopurinol initiation were motivation to prevent gout flares and trust in the advice of their healthcare professionals (HCPs). Reluctance to commence long-term medication was a barrier to allopurinol initiation. Believing in the effectiveness and necessity of allopurinol and reminder systems were facilitators of implementation. Barriers to implementation included forgetfulness, gout flares and limited feedback on allopurinol's effectiveness. Patients discontinued therapy when allopurinol was perceived as ineffective or unnecessary. Discontinuation coincided with patients experiencing gout flares while adhering to allopurinol and receiving suboptimal advice about gout management. Patients identified receiving accurate advice from HCPs and regular urate monitoring for feedback on allopurinol's effectiveness as potential strategies to improve adherence. Perceived benefits of self-monitoring urate as a strategy to promote adherence included the ability to self-manage gout and make informed decisions about allopurinol therapy with their HCP.. Patient perceptions of the effectiveness and necessity of allopurinol influenced intentional adherence during medication initiation, implementation and discontinuation. Strategies that inform patients of their urate control and provide accurate medical advice have the potential to improve adherence to allopurinol.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Medication Adherence; Uric Acid

To evaluate the influence of febuxostat on adverse events and mortality in gout.. We retrospectively enrolled patients with newly diagnosed gout and prescribed urate-lowering therapy between 2006 and 2017 from the Taiwan National Health Insurance Database. These patients were divided into 2 groups: with and without comorbidities (n = 294 847 and 194 539). An interrupted time series analysis with adjustments for demographics, comorbidities, and comedication by propensity score-based stabilized weights was used to compare the trend of adverse events and mortality before vs after febuxostat was introduced in 2012.. The proportion of febuxostat use gradually increased from 0% in 2012 to 30% in those with comorbidities and 10% in those without comorbidities in 2017. Allopurinol use decreased from 30% in 2012 to 10% in 2017. The slope of the 1-year incidence rate of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (per 10 000 patients) significantly reduced after 2012 in those with and without comorbidities (-0.375 per quarter, P = .015 and -.253 per quarter, P = .049). The slope of the 3-year incidence rate of acute myocardial infarction (AMI) (per 1000 patients), percutaneous coronary intervention (PCI) (per 1000 patients), and all-cause mortality (per 100 patients) significantly increased after 2012 in those with comorbidities (+0.207 per quarter, P = .013; +.389 per quarter, P = .002; +.103 per quarter, P = .001).. Febuxostat may reduce SJS and TEN in all gout patients but increase AMI, PCI, and all-cause mortality in gout patients with comorbidities.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Interrupted Time Series Analysis; Myocardial Infarction; Percutaneous Coronary Intervention; Retrospective Studies; Taiwan

Gout is the most common inflammatory arthritis with an increasing prevalence and incidence across the globe. We aimed to provide a comprehensive and systematic knowledge map of gout research to determine its current status and trends over the past decade.. Publications on gout research were obtained from the Web of Science Core Collection (WOSCC) database. Bibliometric R, VOSviewer, and Citespace were employed to analyze the eligible literature.. A total of 5535 publications concerning gout research between 2012 and 2021 were included. Most publications and citations both numerically came from China. The strongest international cooperation belonged to the USA. The University of Auckland was the most productive institution with a leading place in research collaboration. The prime funding agency was the National Natural Science Foundation of China. Most papers were published in Clinical Rheumatology. Annals of the Rheumatic Diseases achieved the highest number of citations, H-index and IF, which showed the most excellent comprehensive strength. The individual author with the most paper authorship was Dalbeth Nicola with 241 publications and 46 H-index. Keywords and co-citation analysis discovered that pathological mechanism remains the future hotspot in gout research. It may involve gout connection with gut microbiota, NLRP3 inflammasome, xanthine oxidase, and urate-transporter ABCG2. In addition, besides metabolic diseases, the relationship between gout and heart failure may need more attention.. This study clarified the current status and research frontier in gout over the past decade, which would provide valuable research references for later researchers. Key Points •We disclosed the current status and frontier directions of gout over the past 10 years worldwide. •We identified future hotspots of gout research, including gout connection with gut microbiota, NLRP3 inflammasome, xanthine oxidase, and urate-transporter ABCG2. •We discovered that the relationship between gout and heart status would be the research frontier.

Topics: Bibliometrics; Gout; Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Uric Acid; Xanthine Oxidase

Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown.. We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs).. The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs.. In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Topics: Allopurinol; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Male; Prevalence; Quality of Life; Renal Dialysis

To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system.. A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed.. Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results.. From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China's health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.

Topics: Allopurinol; China; Cost-Benefit Analysis; East Asian People; Febuxostat; Gout; Gout Suppressants; HLA-B Antigens; Humans; Quality-Adjusted Life Years; Renal Insufficiency, Chronic

Xanthine oxidase (XO) plays a critical role in the progression of gout. We showed in a previous study that Sanghuangporus vaninii (S. vaninii), a perennial, medicinal, and edible fungus traditionally used to treat various symptoms, contains XO inhibitors. In the current study, we isolated an active component of S. vaninii using high performance countercurrent chromatography and identified it as davallialactone using mass spectrometry with 97.726 % purity. A microplate reader showed that davallialactone had mixed inhibition of XO activity with a half-inhibitory concentration value of 90.07 ± 2.12 μM. In addition, the collision between davallialactone and XO led to fluorescence quenching and conformational changes in XO, which were mainly driven by hydrophobicity and hydrogen bonding. Molecular simulations further showed that davallialactone was located at the center of the molybdopterin (Mo-Pt) of XO and interacted with amino acid residues Phe798, Arg912, Met1038, Ala1078, Ala1079, Gln1194, and Gly1260, suggesting that entering the enzyme-catalyzed reaction was unfavorable for the substrate. We also observed face-to-face π-π interactions between the aryl ring of davallialactone and Phe914. Cell biology experiments indicated that davallialactone reduced the expression of the inflammatory factors, tumor necrosis factor alpha and interleukin-1 beta (P < 0.05), can effectively alleviate cellular oxidative stress. This study showed that davallialactone significantly inhibits XO and has the potential to be developed into a novel medicine to prevent hyperuricemia and treat gout.

Topics: Basidiomycota; Enzyme Inhibitors; Gout; Humans; Molecular Docking Simulation; Xanthine Oxidase

Topics: Allopurinol; Benzbromarone; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid

Topics: Gout; Humans; Hyperuricemia; Xanthine Oxidase

Hyperuricemia (HUA) is a metabolic disease caused by abnormal purine metabolism in the body. It also shows a trend of high incidence among younger people worldwide. More and more studies have shown that natural products can be used to treat HUA, and the literature in this field has been increasing in recent years. However, few bibliometric analyses have systematically examined this field. Our study aims to analyze the published literature to identify trends and hotspots in natural product therapy for HUA, present the research status and summarize critical topics.. A literature search was conducted through the Web of Science Core Collection (WOSCC) database, using Bibliometric R, VOS Viewer, and CiteSpace to examine the eligible publications. A total of 1,201 publications (1,040 articles and 161 reviews) concerning natural product therapy for HUA research between 2000 and 2021 were ultimately included.. In recent years, research articles in this field have increased. China and the United States are the main driving forces in this field and have a high academic reputation. China published the most relevant articles, while the United States cited the most. Chinese Acad Sci is the institution with the most relevant research results. Flavonoids, xanthine oxidase, antioxidant activity, and gout are the current research hotspots and future research trend topics.. Our results provide a general overview of the leading research directions of natural products in HUA research. The mechanisms of natural products, especially those related to xanthine oxidase, antioxidant activity, and gout, may soon become hot spots and should be closely watched. The field of natural product therapy for HUA is going through rapid development, and our research provides a valuable reference for clinical researchers and practitioners.

Topics: Antioxidants; Biological Products; Gout; Humans; Hyperuricemia; Xanthine Oxidase

Prescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood.. To examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use.. This retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019.. The US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010.. Mean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023.. A total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P < .001). Meanwhile, adjusted allopurinol use rose by 7.8 (95% CI, 6.9-8.7) pills per patient in year 1, a 7.6% increase from baseline, and by 33.1 (95% CI, 32.6-33.7) pills per patient through 2019, a 32.0% increase from baseline over the decade (P < .001). Moreover, adjusted oral corticosteroid use exhibited no significant change in the first year, then increased by 1.5 (95% CI, 1.3-1.7) pills per patient through 2019, an 8.3% increase from baseline over the decade. Adjusted ED visits for gout rose by 0.02 (95% CI, 0.02-0.03) per patient in year 1, a 21.5% increase, and by 0.05 (95% CI, 0.04-0.05) per patient through 2019, a 39.8% increase over the decade (P < .001). Adjusted rheumatology visits for gout increased by 0.02 (95% CI, 0.02-0.03) per patient through 2019, a 10.5% increase over the decade (P < .001).. In this cohort study among individuals with gout, the large increase in colchicine prices in 2010 was associated with an immediate decrease in colchicine use that persisted over approximately a decade. Substitution with allopurinol and oral corticosteroids was also evident. Increased ED and rheumatology visits for gout over the same period suggest poorer disease control.

Topics: Adolescent; Adrenal Cortex Hormones; Allopurinol; Cohort Studies; Colchicine; Delivery of Health Care; Female; Gout; Gout Suppressants; Humans; Male; Prescription Drugs; Retrospective Studies

The aim of this study was to quantify identifiable sources of variability, including key pharmacogenetic variants in oxypurinol pharmacokinetics and their pharmacodynamic effect on serum urate (SU).. Hmong participants (n = 34) received 100 mg allopurinol twice daily for 7 days followed by 150 mg allopurinol twice daily for 7 days. A sequential population pharmacokinetic pharmacodynamics (PKPD) analysis with non-linear mixed effects modelling was performed. Allopurinol maintenance dose to achieve target SU was simulated based on the final PKPD model.. A one-compartment model with first-order absorption and elimination best described the oxypurinol concentration-time data. Inhibition of SU by oxypurinol was described with a direct inhibitory E. The proposed allopurinol dosing guide uses individuals' fat-free mass, renal function and SLC22A12 rs505802 and PDZK1 rs12129861 genotypes to achieve target SU.

Topics: Adult; Allopurinol; Gout; Gout Suppressants; Humans; Hyperuricemia; Organic Anion Transporters; Organic Cation Transport Proteins; Oxypurinol; Pharmacogenetics

Pathophysiologic processes promoted by uric acid, including inflammation and oxidative stress, play a key role in the pathogenesis of several cardiovascular diseases. Furthermore, a number of epidemiological studies have shown an association between uric acid plasma levels and multiple cardiovascular risk factors. This ANMCO statement provides an update on available evidence regarding the association between elevated plasma uric acid levels and cardiovascular disease risk and the safety and efficacy of uric acid lowering agents (allopurinol and febuxostat) used in patients with urate crystal deposits. In addition, it summarizes practical indications for the use of these drugs in at-risk patients or in patients with cardiovascular disease.

Topics: Allopurinol; Cardiovascular Diseases; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid

There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid-lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea.. This study used data from a national HD quality assessment program and the claims data. Use of ULDs was defined as more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups. Patients who were not prescribed allopurinol or febuxostat were included in group 1 (n = 43,251); patients who were prescribed allopurinol were included in group 2 (n = 9,987); and patients who were prescribed febuxostat were included in group 3 (n = 2,890).. Kaplan-Meier curves showed that the survival rate was greatest in group 3 and worst in group 1 among the three groups. Multivariable analysis showed that group 2 had better patient survival compared to group 1; however, there was no significant difference in patient survival between groups 2 and 3. In addition, patients with hyperuricemia or gout had better patient survival compared to those without these diseases.. Our study showed that survival in patients receiving ULDs was not inferior to that of those not receiving ULDs. Patient survival between patients on HD receiving allopurinol and those receiving febuxostat was similar.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Dialysis; Treatment Outcome; Uric Acid

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid

We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database.. Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis.. This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041).. Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Topics: Adult; Allopurinol; Colchicine; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Insurance Claim Review; Insurance, Health; Republic of Korea; Retrospective Studies; Uric Acid; Xanthine Oxidase; Young Adult

Hyperuricemia is an important pathological basis of gout and a distinct hazard factor for metabolic syndromes and cardiovascular and chronic renal disease, but lacks safe and effective treatments currently. Paeonia × suffruticosa Andrews leaf effectively reduced serum uric acid in gout patients; however, the material foundation and the mechanism remain unclear.. To determine the primary active components and mechanism of P. suffruticosa leaf in hyperuricemic mice.. The chemical constituents of P. suffruticosa leaf was identified using high-performance liquid chromatographic analysis. The anti-hyperuricemic activity of P. suffruticosa leaf extract (12.5, 25, 50, 100, and 200 mg/kg) and its components was evaluated in hyperuricemic mice induced by a high purine diet for 14 days. Then, the urate-lowering effects of apigenin 7-O-glucoside (0.09, 0.18, and 0.36 mg/kg) were assessed in another hyperuricemic mice model built by administrating potassium oxonate and adenine for 4 weeks. The inhibitory effect of apigenin 7-O-glucoside on uric acid production was elucidated by investigating xanthine oxidase activity in vitro and in serum and the liver and through molecular docking. Immunofluorescence and western blot analyses of the expression of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), and ATP-binding cassette G member 2 (ABCG2) proteins elucidated how apigenin 7-O-glucoside promoted uric acid excretion.. Six compounds were identified in P. suffruticosa leaf: gallic acid, methyl gallate, oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, and apigenin 7-O-glucoside. P. suffruticosa leaf extract significantly attenuated increased serum uric acid, creatinine, and xanthine oxidase activity in hyperuricemic mice. Apigenin 7-O-glucoside from P. suffruticosa leaf reduced uric acid, creatinine, and malondialdehyde serum levels, increased superoxide dismutase activity, and partially restored the spleen coefficient in hyperuricemic mice. Apigenin 7-O-glucoside inhibited xanthine oxidase activity in vitro and decreased serum and liver xanthine oxidase activity and liver xanthine oxidase protein expression in hyperuricemic mice. Molecular docking revealed that apigenin 7-O-glucoside bound to xanthine oxidase. Apigenin 7-O-glucoside facilitated uric acid excretion by modulating the renal urate transporters URAT1, GLUT9, OAT1, and ABCG2. Apigenin 7-O-glucoside protected against renal damage and oxidative stress caused by hyperuricemia by reducing serum creatinine, blood urea nitrogen, malondialdehyde, and renal reactive oxygen species levels; increasing serum and renal superoxide dismutase activity; restoring the renal coefficient; and reducing renal pathological injury.. Apigenin 7-O-glucoside is the main urate-lowering active component of P. suffruticosa leaf extract in the hyperuricemic mice. It suppressed liver xanthine oxidase activity to decrease uric acid synthesis and modulated renal urate transporters to stimulate uric acid excretion, alleviating kidney damage caused by hyperuricemia.

Topics: Animals; Apigenin; Creatinine; Glucosides; Gout; Hyperuricemia; Kidney; Malondialdehyde; Mice; Molecular Docking Simulation; Organic Anion Transporters; Oxonic Acid; Paeonia; Superoxide Dismutase; Uric Acid; Xanthine Oxidase

Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported.. To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population.. Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout.. Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia.. This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

Topics: Allopurinol; Dementia; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Prevalence

To determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout.. We conducted two matched retrospective cohort studies in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with (1) colchicine or (2) NSAID prophylaxis were compared with those initiating without prophylaxis, individually matched by age, sex and propensity to receive the relevant prophylaxis. Weighted Cox proportional hazards models investigated associations between colchicine/NSAID and specified adverse events.. 13 945 individuals prescribed colchicine were matched to 13 945 with no prophylaxis and 25 980 prescribed NSAID to 25 980 with no prophylaxis. Adverse event incidence rates were <200/10 000 patient-years except diarrhoea (784.4; 95% CI 694.0 to 886.5) and nausea (208.1; 95% CI 165.4 to 261.7) for colchicine and angina for NSAID (466.6; 95% CI 417.2 to 521.8). Diarrhoea (HR 2.22; 95% CI 1.83 to 2.69), myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17), neuropathy (4.75; 95% CI 1.20 to 18.76), myalgia (2.64; 95% CI 1.45 to 4.81), bone marrow suppression (3.29; 95% CI 1.43 to 7.58) and any adverse event (1.91, 95% CI 1.65 to 2.20) were more common with colchicine than no prophylaxis, but not nausea/vomiting (1.34; 95% CI 0.97 to 1.85). Angina (1.60; 95% CI 1.37 to 1.86), acute kidney injury (1.56; 95% CI 1.20 to 2.03), MI (1.89; 95% CI 1.44 to 2.48), peptic ulcer disease (1.67; 95% CI 1.14 to 2.44) and any adverse event (1.63; 95% CI 1.44 to 1.85) were more common with NSAID than without.. Adverse events were more common when allopurinol was initiated with prophylaxis, particularly diarrhoea with colchicine. Other events were uncommon, providing reassurance for patients and clinicians to enable shared decision-making.

Topics: Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Colchicine; Diarrhea; Gout; Gout Suppressants; Humans; Myocardial Infarction; Propensity Score; Retrospective Studies; United Kingdom; Uric Acid

Hyperuricemia is a clinical disease characterized by a continuous increase in uric acid (UA) due to purine metabolism disorder. As current drug treatments are limited, it is imperative to explore new drugs that offer better safety and efficacy. In this study, Nephila clavata toxin gland homogenates were isolated and purified by exclusion chromatography and high-performance liquid chromatography, resulting in the identification and isolation of a short peptide (NCTX15) with the sequence 'QSGHTFK'. Analysis showed that NCTX15 exhibited no cytotoxicity in mouse macrophages or toxic and hemolytic activity in mice. Notably, NCTX15 inhibited UA production by down-regulating urate transporter 1 and glucose transporter 9 and up-regulating organic anion transporter 1, thus promoting UA excretion. In addition, NCTX15 alleviated the inflammatory response and renal injury by inhibiting the expression of inflammatory factors interleukin-6, interleukin-1β, tumor necrosis factor alpha, NLR family, pyrin domain-containing 3, and pyroptosis-related factor gasdermin D. These results indicate that NCTX15 displayed urate-lowering, anti-inflammatory, and analgesic effects. As the first urate-reducing short peptide isolated from a spider toxin gland homogenate, NCTX15 exhibits considerable potential as a novel drug molecule for anti-gout and hyperuricemia treatment.

Topics: Animals; Gout; Hyperuricemia; Interleukin-6; Kidney; Mice; Uric Acid; Xanthine Oxidase

Musculoskeletal disorders are one of the most common reasons military servicemen seek medical care during their line of duty. This study aims to review the clinical profile and outcomes of military personnel with inflammatory arthritis (IA) referred to a specialist rheumatology center in Singapore.. Consecutive new case referrals from the Singapore Armed Forces medical centers during the study period January 1, 2010, to December 31, 2019, were retrospectively studied.. There were 123 referrals, comprising 112 (91.1%) males, with the majority being Chinese (110, 89.4%). The mean age was 25.5 ± 11.1 years. The most common diagnoses were gout (including chronic tophaceous gout; 34, 27.6%), spondyloarthritis (18, 14.6%), palindromic rheumatism (8, 6.5%), rheumatoid arthritis (4, 3.3%), and juvenile idiopathic arthritis (4, 3.3%). Among servicemen with gout, all were male, the majority (31, 91.3%) were Chinese, and mean age was 34.1 ± 8.8 years. Mean body mass index (BMI) was 27.5 ± 3.9 kg/m2, of which 41.2% had moderate-risk and 47.1% high-risk BMI for cardiovascular disease and diabetes mellitus (DM). Comorbidities included hyperlipidemia (14), hypertension (6), and type 2 DM (3). Urate lowering therapy was initiated in 27 (79.4%) patients, comprising allopurinol (85.2%), probenecid (11.1%), and their combination (3.7%). One patient developed allopurinol-induced hepatitis; none had severe cutaneous adverse reactions. Among the remaining patients with IA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) used were sulfasalazine (8), methotrexate (4), hydroxychloroquine (4), and leflunomide (2). Biologic DMARDs used in five patients comprised adalimumab (3) and golimumab (2).. Servicemen with IA and good functional status can still be physically fit and deployable into certain combat and service support vocations. This will optimize manpower resources in military organizations with a shrinking young workforce.

Topics: Adolescent; Adult; Allopurinol; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Gout; Humans; Male; Military Personnel; Retrospective Studies; Rheumatology; Singapore; Young Adult

Topics: Allopurinol; Gout; Gout Suppressants; Humans

To evaluate the impact of incorporating treatment guidance into reporting of urate test results.. Urate targets for clinically confirmed gout were added to urate results above 0.36 mmol/l requested after September 2014 within NHS Lothian. Scotland-wide data on urate-lowering therapy prescriptions and hospital admissions with gout were analysed between 2009 and 2020. Local data on urate tests were analysed between 2014 and 2015.. Admissions with a primary diagnosis of gout in Lothian reduced modestly following the intervention from 111/year in 2010-2014 to 104/year in 2015-2019, a non-significant difference (P = 0.32). In contrast there was a significant increase in admissions to remaining NHS Scotland health boards (556/year vs 606/year, P < 0.01). For a secondary diagnosis of gout the number of admissions in NHS Lothian reduced significantly (58/year vs 39/year, P < 0.01) contrasting with a significant increase in remaining Scottish health boards (220/year vs 290/year, P < 0.01). The relative rate of admissions to NHS Lothian compared with remaining Scottish boards using a 2009 baseline were significantly reduced for both primary diagnosis of gout (1.06 vs 1.25, P < 0.001) and secondary diagnoses of gout (0.64 compared with 1.4, P < 0.001) after the intervention; however, there was no difference before the intervention. A relative increase in the prescription rates of allopurinol 300 mg tablets and febuxostat 120 mg tablets may have contributed to the improved outcomes seen.. Incorporation of clinical guideline advice into routine reporting of urate results was associated with reduced rates of admission with gout in NHS Lothian, in comparison with other Scottish health boards.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Hospitals; Humans; Treatment Outcome; Uric Acid

The purpose of this study was to explore the hypouricemic effect in hyperuricemia mice of triterpenoid acids from Inonotus obliquus (TAIO), and decipher of the underlying xanthine oxidase inhibitory mechanism. Measurement of xanthine oxidase (XO) inhibitory activity was assayed. Organ indexes and serum biochemical indicators were measured in potassium oxonate-induced hyperuricemia mice. Studies showed that TAIO had the strong inhibitory effect on XO activity, and its inhibition type was mixed and reversible. In vivo, TAIO decreased efficiently uric acid level, hepatic XO, serum blood urea nitrogen activities in hyperuricemia mice. Indicating that TAIO may ameliorate kidney damage and relieve inflammation in hyperuricemic mice, and had the inhibitory effect on XO activity. Furthermore, eight triterpenoids were identified by Ultra performance liquid chromatography electrospray quadrupole time of flight mass spectrometry. These findings proved that triterpenoids from Inonotus obliquus would have potential biological characteristics and effect on controlling hyperuricemia and gout as an active supplement. PRACTICAL APPLICATIONS: There are a large amount of evidence indicating that hyperuricemia and gout are related to the hypertension and obesity. And gout and hyperuricemia are also possible connection with cardiovascular disease and metabolic syndrome. Currently, xanthine oxidase is the target of many kinds of chemical drugs at present, but the therapeutic drugs used in clinical medicine will produce more or less side effects. Therefore, the aim of this study was to explore the material basis of effective substances for reducing uric acid in Inonotus obliquus and to evaluate its effect. This study can provide a promising application of Inonotus obliquus in the fields of functional foods or medicines for gout and hyperuricemia.

Topics: Agaricales; Animals; Gout; Hyperuricemia; Inflammation; Inonotus; Mice; Triterpenes; Uric Acid; Xanthine Oxidase

Gout is the most common inflammatory arthritis, but was not considered in most COVID-19 and rheumatic diseases reports. Our aim was to describe changes in clinical data, treatment, function and quality of life for gout patients during COVID-19 pandemic.. Prospective, descriptive and analytical study of 101 consecutive gout (ACR/EULAR 2015) patients from our clinic evaluated during pandemic by phone call (n=52) or phone call + face-to-face (n=68) that accepted to participate. Variables are demographics, clinical and treatment data, HAQ, EQ5D questionnaires and COVID-19-related data. Patients were divided in two groups: flare (n=36) or intercritical gout (n=65) also; available pre-pandemic data was obtained from 71 patients. Statistical analyses are X. Included gout patients were males (95.8%), mean (SD) age 54.7 (10.7) years and disease duration 16.4 (9.8) years; 90% received allopurinol, 50% colchicine as prophylaxis and 25% suspended ≥ 1 medication. Comparison of pre-pandemic vs pandemic data showed > flares (4.4% vs 36%, p=0.01), more flares in the last 6 months: 0.31 (0.75) vs 1.71 (3.1), (p=0.004 and > urate levels: 5.6 (1.7)vs 6.7 (2.2) mg/dL, p=0.016. Unexpectedly, function and quality-of-life scores improved: HAQ score 0.65 (2.16) vs 0.12 (0.17), p= 0.001. Seven patients were COVID-19-confirmed cases; they had significantly more flares, higher urate levels and lower allopurinol doses and two died.. In gout patients, flares were 9 times more frequent during pandemic also, they had increased urate levels but led to an unexpected improvement in HAQ and functionality scores. Resilience and lifestyle changes in gout during COVID-19 pandemic require further studies. Key Points • COVID-19 pandemic is associated with 4 times more flares in gout patients. • Increased flares were also seen in previously well-controlled gout patients. • Increased serum urate levels were also found in gout patients during pandemic. • In our gout clinic, 8/101 patients were diagnosed as COVID-19+, and two of them died.

Topics: Allopurinol; COVID-19; Gout; Gout Suppressants; Humans; Male; Middle Aged; Pandemics; Prospective Studies; Quality of Life; SARS-CoV-2; Uric Acid

Topics: Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Treatment Outcome

Topics: Allopurinol; Cohort Studies; Diabetes Mellitus; Gout; Gout Suppressants; Humans; Retrospective Studies

Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.. To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.. Cohort study.. The Health Improvement Network U.K. primary care database (2000 to 2019).. Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.. The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.. Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).. Residual confounding cannot be ruled out.. In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.. Project Program of National Clinical Research Center for Geriatric Disorders.

Topics: Adult; Aged; Allopurinol; Cohort Studies; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome

The objectives of this study were to examine the reasons patients give for nonadherence to allopurinol and to examine differences in intentional nonadherence for patients who did and did not achieve serum urate (SU) levels at treatment target.. Sixty-nine men with gout attending rheumatology clinics, all prescribed allopurinol for ≥ 6 months, completed the Intentional Non-Adherence Scale (INAS). Differences in the types of intentional nonadherence were analyzed between those who did and did not achieve SU at treatment target (< 0.36 mmol/L, 6 mg/dL).. The most frequently endorsed reasons for not taking their urate-lowering therapies (ULT) were because participants wanted to lead a normal life (23%) or think of themselves as a healthy person again (20%). Patients also reported not taking allopurinol as a way of testing if they really needed it (22%). Participants with SU above target endorsed significantly more INAS items as reasons for not taking their medication, had more medicine-related concerns, and were more likely to give Testing treatment as a reason for nonadherence. Participants who were younger, single, and non-New Zealand European also endorsed more reasons for not taking their allopurinol.. The major reasons behind the patient's decision not to take allopurinol relate to the desire to lead a normal life and the strategy of testing the treatment to see if they could reduce the dose without getting symptoms. These results provide some potentially modifiable targets for adherence interventions and some recommendations to clinicians about how to reframe ULT for patients in order to improve adherence.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Male; Rheumatology; Treatment Outcome; Uric Acid

Six male patients with gout were treated with combined oral medication (febuxostat, 120 mg/d, and benzbromarone, 50 or 100 mg/d), aiming at a more rapid success of uric acid lowering treatment (ULT) compared to guideline suggestions. By combined oral medication in moderate dosage, the sUA was reduced to <2 mg/dl in all cases. We conclude that, by the treatment schedule outlined, the majority of patients with gout can be cured within 1 - 2 years, with uricase treatment being necessary very rarely only.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Male; Treatment Outcome; Uric Acid

Over-consumption of foods high in purines like seafood, red meat, and alcoholic beverages leads to hyperuricemia causing gout attacks. Xanthine oxidase was reported responsible for the overproduction of uric acid.. We intend to test in silico and in vitro, the inhibition effect of four vitamins against bovine milk xanthine oxidase (BXO). We performed Molecular docking with GOLD v4.0, and the biological activity prediction with the PASS server. The best-selected vitamins were chosen based on their best PLPchem score. The BXO constant K. The in silico results show that the tested vitamins were the best inhibitors model with PLPchem scores up to 70 comparing to the control. The in vitro results show that BXO have a K. The obtained results promise an excellent strategy using vitamins to enhance immunity, treat hyperuricemia, and minimize the usual drug side effects.

Topics: Enzyme Inhibitors; Folic Acid; Gout; Humans; Hyperuricemia; Kinetics; Molecular Docking Simulation; Structure-Activity Relationship; Vitamins; Xanthine Oxidase

To explore the frequency and predictors of flares over 2 years during a treat-to-target strategy with urate-lowering therapy (ULT) in patients with gout.. In the treat-to-target, tight control NOR-Gout study patients started ULT with escalating doses of allopurinol. Flares were recorded over 2 years. Baseline predictors of flares during months 9-12 in year 1 and during year 2 were analyzed by multivariable logistic regression.. Of 211 patients included (mean age 56.4 years, disease duration 7.8 years, 95% males), 81% (150/186) of patients experienced at least one gout flare during the first year and 26% (45/173) during the second year. The highest frequency of flares in the first year was seen during months 3-6 (46.8% of patients). Baseline crystal depositions detected by ultrasound and by dual-energy computed tomography (DECT) were the only variables which predicted flares both during the first period of interest at months 9-12 (OR 1.033; 95% CI 1.010-1.057, and OR 1.056; 95% CI 1.007-1.108) and also in year 2. Baseline subcutaneous tophi (OR 2.42, 95% CI 1.50-5.59) and prior use of colchicine at baseline (OR 2.48, 95% CI 1.28-4.79) were independent predictors of flares during months 9-12, whereas self-efficacy for pain was a protective predictor (OR 0.98 per unit, 95% CI 0.964-0.996).. In patients with gout, flares remain frequent during the first year of a treat-to-target ULT strategy, especially during months 3-6, but are much less frequent during year 2. Baseline crystal depositions predict flares over 2 years, supporting ULT early during disease course.. ACTRN12618001372279.

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Symptom Flare Up; Uric Acid

Patients with hyperuricemia and gout are at an increased risk for cardiovascular (CV) disease. Inhibition of the xanthine oxidase with allopurinol or febuxostat have become the mainstay for urate lowering therapy. However, it has been suggested that febuxostat increases the risk for CV mortality as compared to allopurinol. The aim of this retrospective cohort study was to assess the CV risk among patients with febuxostat or allopurinol therapy. Patients who initiated urate lowering therapy with febuxostat or allopurinol between 2014 and 2017 were selected from the drug reimbursement database of the Austrian health insurances funds. The primary CV endpoint was a composite of angina pectoris, nonfatal myocardial infarction, nonfatal subarachnoid or cerebral hemorrhage, nonfatal ischemic stroke, or death from any cause. In total, 28.068 patients (62.1% male) with a mean age of 71 years were included. 7.767 initiated febuxostat treatment and 20.301 received allopurinol. The incidence rate per 100 patient-years of the composite primary endpoint was 448 (febuxostat) and 356 (allopurinol) with a corresponding adjusted hazard ratio (HR) of 0.58 (95% CI 0.53-0.63) for allopurinol vs. febuxostat initiators. Similar HR were found for secondary endpoints including all-cause mortality [0.61 (95% CI 0.55-0.68)] and separate analyses of cardiac events [0.48 (95% CI 0.38-0.61)] and ischemic stroke [0.47 (95% CI 0.36-0.61)]. Data from this Austrian population-based study suggests that febuxostat initiators are at an increased risk for nonfatal CV events or death from any cause as compared to those with allopurinol. This is consistent with CV concerns of other trials, which limited the broad therapeutic use of febuxostat.

Topics: Aged; Allopurinol; Austria; Cardiovascular Diseases; Cohort Studies; Febuxostat; Female; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Hyperuricemia; Ischemic Stroke; Male; Retrospective Studies; Risk Factors; Uric Acid

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans

Gout is a common disease caused by hyperglycemia. Traditional drugs for gout have both good therapeutic effects and serious side effects. Traditional Chinese medicine (TCM) is one of the potential sources of modern medicine, and is the development of new drugs for many diseases, including gout. TCM is an indispensable part of gout treatment. Compared with anti-gout medication commonly used in clinic (e.g. the xanthine oxidase inhibitors allopurinol and febuxostat), traditional Chinese medicine has fewer side effects in the treatment of gout and can safely control serum uric acid and the level of inflammation. However, there have been few studies on how traditional Chinese medicine controls uric acid and inflammation levels in patients with gout.. Herbs are a valuable resource in the search for new drugs to treat many diseases, including gout. Phytochemicals in TCM treatment of gout mainly includes two aspects, anti-inflammatory and reducing uric acid content. The anti-inflammatory mechanism is mainly through the inactivation of NF-κB and NLRP3 inflammasome to reduce the inflammatory response induced by uric acid crystals. The mechanism of lowering uric acid is mainly through inhibiting the activity of xanthine oxidase and up-regulating the expression of URAT1 and GLUT9.In recent years, the intestinal flora has become a new field of understanding diseases. It has been observed that the occurrence of gout is closely related to changes in the intestinal flora. Herbaceous plants contain fiber, polyphenols, polysaccharides and other active components. When taken orally, Chinese herbs act like prebiotics. After traditional Chinese medicine treatment, the abundance levels of Bifidobacterium, Lactobacillus, Bacteroidetes and Prevotella were increased, while the abundance of Proteus and the Firmicutes/Bacteroidetes ratio were decreased. Changes in the intestinal flora led to further changes in its metabolites, including short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS), which ultimately down-regulate the TLR4/NF-κB inflammatory signaling pathway, up-regulate GLUT9 and URAT1 gene expression and inhibition of xanthine oxidase activity. Destruction of the intestinal barrier is also an important factor in the occurrence of gout. Disruption of the intestinal barrier allows LPS to enter the bloodstream and activates the expression of various inflammatory factors, which causes gout.

Topics: Gastrointestinal Microbiome; Gout; Humans; Hyperuricemia; Inflammation; Lipopolysaccharides; Medicine, Chinese Traditional; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Phytochemicals; Uric Acid; Xanthine Oxidase

Gout is the most common form of inflammatory arthritis in men. Despite the availability of effective urate-lowering therapies (ULT), the management of gout is suboptimal due to poor persistence with ULT. This study examined national prescribing patterns of ULT to determine persistence with allopurinol in Australia.. A 10% sample of the Australian Pharmaceutical Benefits Scheme dispensing claims database was used to identify individuals initiated on allopurinol between April 2014 and December 2019. The number of allopurinol scripts dispensed was used to estimate persistence with allopurinol. Persistence was defined as the number of months from initiation until discontinuation (last prescription with no further scripts acquired for a period thereafter). Kaplan-Meier curves were used to examine persistence, while Cox regression analysis was used to examine the influence of gender, concomitant colchicine and age.. The largest drop in persistence occurred immediately after initiation, with 34% of patients discontinuing allopurinol 300-mg therapy in the first month. Median persistence with allopurinol 300 mg was 5 months (95% confidence interval 4.76-5.24), with around 63% of individuals not persisting with this therapy for more than 12 months. Concomitant prescription of colchicine on the day of allopurinol initiation only occurred in 7% of allopurinol initiations. No increase in persistence was observed for those co-prescribed colchicine.. Persistence with allopurinol was poor. More effective methods targeting prescribers, patients and systems are required to promote persistence with allopurinol. Improving persistence to allopurinol is an important public health goal given the proven potential of this medication to eliminate gout.

Topics: Allopurinol; Australia; Colchicine; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Pharmaceutical Preparations; Prescriptions; Uric Acid

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome

The Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) trial suggested a higher risk of cardiovascular (CV) death from febuxostat than from allopurinol. However, a significant number of patients died after discontinuation of febuxostat or allopurinol. We investigated whether major adverse cardiovascular events (MACE) and CV death were increased because of discontinuation of febuxostat or allopurinol using the CARES trial data.. We compared the MACE that occurred during administration and after discontinuation in the initial phase after discontinuation, and we compared the CV and non-CV mortality rates in the initial phase after discontinuation to determine the impact of discontinuation of febuxostat or allopurinol.. Among 6190 patients, the incidence rate per 100 person-years for MACE was 3.11 during administration and 6.71 after discontinuation. MACE was significantly increased after discontinuation compared with that during administration within 1 month (HR 7.40; 95% CI 5.38 to 10.17) and 6 months (HR 5.22; 95% CI 4.26 to 6.39). In the analysis excluding death induced by adverse events that occurred up to 1 day after the last medication, the CV mortality rate was higher than the non-CV mortality rate within 6 months (45.7% vs 27.9%, p=0.0001). In addition, changes in serum uric acid levels from baseline to the last measurement before discontinuation were significantly associated with higher MACE risk after drug discontinuation (HR 1.14; 95% CI 1.04 to 1.26).. MACE and CV death were increased in the initial stage after discontinuation of febuxostat or allopurinol in patients with gout.

Topics: Allopurinol; Cardiovascular Diseases; Clinical Trials as Topic; Febuxostat; Gout; Gout Suppressants; Humans

Topics: Allopurinol; Cohort Studies; COVID-19; Gout; Gout Suppressants; Humans; Pandemics; Uric Acid

Corni fructus is consumed as food and herbal medicine in Chinese culture. Studies have revealed that corni fructus exhibits potent antioxidant activity; however, few studies have investigated the ability of corni fructus to lower uric acid concentrations. In this study, the xanthine oxidase (XO) inhibition and uric acid-lowering effect of corni fructus extract (CFE) were evaluated in mice with potassium oxonate-induced hyperuricemia. Hyperuricemia is a chronic disease prevalent worldwide and is associated with high recurrence rates. In addition, drugs used to treat hyperuricemia induce side effects that discourage patient compliance. Hyperuricemia induces metabolic imbalances resulting in accumulative uric acid deposition in the joints and soft tissues. Hyperuricemia not only induces gout but also interrupts hepatic and renal function, thereby trigging severe inflammation and various complications, including obesity, nonalcoholic fatty liver disease, diabetes, and metabolic diseases. In this study, the ethyl acetate fraction (EAF) of CFE resulted in yields of antioxidant photochemical components significantly higher than those of CFEs formed using other substances. The EAF of CFE exhibited high free radical scavenging activity and XO inhibition and effectively lowered uric acid concentrations in the animal model of chemically induced hyperuricemia. The results of this study can serve as a reference for the prevention of preclinical gout as well as for functional food research.

Topics: Animals; Antioxidants; Cornus; Gout; Hyperuricemia; Mice; Oxonic Acid; Plant Extracts; Uric Acid; Xanthine Oxidase

Automated checks for medication-related problems have become a cornerstone of medication safety. In many clinical settings medication checks remain confined to drug-drug interactions because only medication data are available in an adequately coded form, leaving possible contraindicated drug-disease combinations unaccounted for. Therefore, we devised algorithms that identify frequently contraindicated diagnoses based on medication patterns related to these diagnoses.. We identified drugs that are associated with diseases constituting common contraindications based on their exclusive use for these conditions (such as allopurinol for gout or salbutamol for bronchial obstruction). Expert-based and machine learning algorithms were developed to identify diagnoses based on highly specific medication patterns. The applicability, sensitivity and specificity of the approach were assessed by using an anonymized real-life sample of medication and diagnosis data excerpts from 3506 discharge records of geriatric patients.. Depending on the algorithm, the desired focus (i.e., sensitivity vs. specificity) and the disease, we were able to identify the diagnoses gout, epilepsy, coronary artery disease, congestive heart failure and bronchial obstruction with a specificity of 44.0-99.8% (95% CI 41.7-100.0%) and a sensitivity of 3.8-83.1% (95% CI 1.0-86.1%). Using only medication data, we were able to identify 123 (51.3%) of 240 contraindications identified by experts with access to medication data and diagnoses.. This study provides a proof of principle that some key diagnosis-related contraindications can be identified based on a patient's medication data alone, while others cannot be identified. This approach offers new opportunities to analyse drug-disease contraindications in community pharmacy or clinical routine data.

Topics: Aged; Algorithms; Allopurinol; Documentation; Drug Interactions; Gout; Humans

Linked metabolic and cardiovascular comorbidities are prevalent in hyperuricemia and gout. For mechanistic insight into impact on inflammatory processes and cardiometabolic risk factors of xanthine oxidase inhibitor urate-lowering therapy (ULT) titration to target, we performed a prospective study of gout serum metabolomes from a ULT trial.. Sera of gout patients meeting the 2015 ACR/EULAR gout classification criteria (n = 20) and with hyperuricemia were studied at time zero and weeks 12 and 24 of febuxostat or allopurinol dose titration ULT. Ultrahigh performance liquid chromatography-tandem mass spectroscopy acquired the serum spectra. Data were assessed using the Metabolon and Metaboloanalyst software. Lipolysis validation assays were done in febuxostat and/or colchicine-treated 3T3-L1 differentiated adipocytes.. Serum urate decreased from time zero (8.21 ±1.139 SD) at weeks 12 (5.965 ± 1.734 SD) and 24 (5.655 ±1.763 SD). Top metabolites generated by changes in nucleotide and certain amino acid metabolism and polyamine pathways were enriched at 12 and 24 weeks ULT, respectively. Decreases in multiple fatty acid metabolites were observed at 24 weeks, linked with obesity. In cultured adipocytes, febuxostat significantly decreased while colchicine increased the lipolytic response to β-adrenergic-agonism or TNF.. Metabolomic profiles linked xanthine oxidase inhibitor-based ULT titration to target with reduced serum free fatty acids. In vitro validation studies revealed that febuxostat, but not colchicine, reduced lipolysis in cultured adipocytes. Since soluble urate, xanthine oxidase inhibitor treatment, and free fatty acids modulate inflammation, our findings suggest that by suppressing lipolysis, ULT could regulate inflammation in gout and comorbid metabolic and cardiovascular disease.

Topics: Adipocytes; Allopurinol; Colchicine; Enzyme Inhibitors; Fatty Acids, Nonesterified; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Inflammation; Lipolysis; Prospective Studies; Uric Acid; Xanthine Oxidase

Gout is an inflammatory joint disease caused by urate crystal deposition, which is associated with hyperuricemia. Gout will take place when the uric acid accumulates. Xanthine oxidase (XO) is a crucial enzyme in the formation of uric acid. Inhibiting XO is one of the means to ameliorate gout. Luteoloside is a kind of natural flavonoid, which has an excellent prospect for relieving gout. But there are few reports on the interaction mechanism between luteoloside and XO currently. In this study, the interaction mechanism between luteoloside and XO was explored using spectroscopy and molecular docking. The fluorescence spectroscopy results indicated that luteoloside could make the intrinsic fluorescence of XO quenched, and the binding constant between luteoloside and XO was (1.85 ± 0.22) × 10

Topics: Enzyme Inhibitors; Gout; Humans; Molecular Docking Simulation; Spectrometry, Fluorescence; Uric Acid; Xanthine Oxidase

Abnormal uric acid level result in the development of hyperuricemia and hallmark of various diseases, including renal injury, gout, cardiovascular disorders, and non-alcoholic fatty liver. This study was designed to explore the anti-inflammatory potential of stevia residue extract (STR) against hyperuricemia-associated renal injury in mice. The results revealed that STR at dosages of 150 and 300 mg/kg bw and allopurinol markedly modulated serum uric acid, blood urea nitrogen, and creatinine in hyperuricemic mice. Serum and renal cytokine levels (IL-18, IL-6, IL-1Β, and TNF-α) were also restored by STR treatments. Furthermore, mRNA and immunohistochemistry (IHC) analysis revealed that STR ameliorates UA (uric acid)-associated renal inflammation, fibrosis, and EMT (epithelial-mesenchymal transition) via MMPS (matrix metalloproteinases), inhibiting NF-κB/NLRP3 activation by the AMPK/SIRT1 pathway and modulating the JAK2-STAT3 and Nrf2 signaling pathways. In summary, the present study provided experimental evidence that STR is an ideal candidate for the treatment of hyperuricemia-mediated renal inflammation. PRACTICAL APPLICATIONS: The higher uric acid results in hyperuricemia and gout. The available options for the treatment of hyperuricemia and gout are the use of allopurinol, and colchicine drugs, etc. These drugs possess several undesirable side effect. The polyphenolic compounds are abundantly present in plants, for example, stevia residue extract (STR) exert a positive effect on human health. From this study results, we can recommend that polyphenolic compounds enrich STR could be applied to develop treatment options for the treatment of hyperuricemia and gout.

Topics: Allopurinol; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Colchicine; Creatinine; Drugs, Chinese Herbal; Gout; Humans; Hyperuricemia; Inflammation; Interleukin-18; Interleukin-6; Kidney; Mice; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; RNA, Messenger; Sirtuin 1; Stevia; Tumor Necrosis Factor-alpha; Uric Acid

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Treatment Outcome; Uric Acid

To re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat.. Using 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).. We included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat.. In this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

Topics: Allopurinol; Cohort Studies; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Myocardial Infarction; Treatment Outcome

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans

As the development of hyperuricemia (HUA) and gout continues to accelerate worldwide, there is increasing interest in the use of xanthine oxidase (XO) inhibitors as therapeutic agents for the management of HUA and gout. In the present study, XO inhibitory peptides were identified from whey protein isolate (WPI) hydrolysates, and the underlying inhibitory mechanism and in vivo activities was investigated. WPI hydrolysates were isolated and purified, and two peptides (ALPM and LWM) with lower binding energy were screened by molecular docking. The result showed that these two peptides interacted with residues around the active site of XO through hydrogen bond and hydrophobic interaction. The IC

Topics: Animals; Enzyme Inhibitors; Gout; Hyperuricemia; Molecular Docking Simulation; Peptides; Whey Proteins; Xanthine Oxidase

In health-care, there is a need to quantify medical errors. Among these errors, we observe wrong dose prescriptions. Drug dose titration (DT) is the process by which dosage is progressively adjusted to the patient till a steady dose is reached. Depending on the clinical disease, drug, and patient condition, dose titration can follow different procedures. Once modeled, these procedures can serve for clinical homogenization, standardization, decision support and retrospective analysis. Here, we propose a language to model dose titration procedures. The language was used to formalize one- and two-drug titration of chronic and acute cases, and to perform retrospective analysis of the drug titration processes on 253 patients diagnosed of diabetes mellitus type 2 and treated with metformin, 321 patients treated of chonic heart failure with furosemide, 155 patients with hyperuricemia treated with allopurinol as initial drug and febuxostat as alternative drug, and 187 hyperuricemia patients with primary drug allopurinol and supplementary drug probenecid, in order to identify different types of drug titration deviations from standard DT methods.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Hyperuricemia; Retrospective Studies; Uric Acid

Topics: Animals; Enzyme Inhibitors; Febuxostat; Gout; Hyperuricemia; Mice; Triazoles; Xanthine Dehydrogenase; Xanthine Oxidase

Topics: Allopurinol; Gout; HLA-B Antigens; Humans

To evaluate and compare the risk of erectile dysfunction (ED) associated with the use of allopurinol and febuxostat in adult male gout patients.. We conducted a cohort study using TriNetX (Cambridge, MA, USA), a global federated health research network that provides real-time electronic medical record datasets. We analyzed and compared the associated risk of ED in gout patients who started taking allopurinol or febuxostat within 12 months. Propensity score matching was performed to adjust for demographic variables, comorbidities, and medication use. Kaplan-Meier analysis was used to estimate the probability of the outcome of interest. The hazard ratio (HR) and associated confidence intervals were calculated along with the proportionality test using R's Survival Package v3.2-3.. We identified 679,862 patients with gout among 107,517,445 patients in the database. Of these patients, 24,000 were treated with febuxostat and 299,726 with allopurinol. After propensity matching, 9075 patients receiving febuxostat without allopurinol (febuxostat group) and 9075 corresponding patients receiving allopurinol without febuxostat (allopurinol group) were analyzed for comparison. Among all male patients over 19 years of age, febuxostat was associated with a significantly higher risk of ED versus allopurinol (HR 1.354; 95% confidence interval (CI) 1.003-1.829; log rank test, p = 0.047). After subgroup analysis, in gout patients aged 19-64 years, a significantly higher incidence of ED was observed in the febuxostat group than in the allopurinol group (HR 2.002, 95% CI 1.282-3.126). The risk of ED did not differ significantly between the allopurinol and febuxostat groups in gout patients older than 65 years.. Febuxostat may be associated with a higher risk of ED than allopurinol in adult male patients with gout. Future large-scale prospective studies are warranted to confirm our results.

Topics: Adult; Allopurinol; Cohort Studies; Erectile Dysfunction; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Male

Topics: Aged; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Medicare; United States

Topics: Aged; Allopurinol; Ethnicity; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Medicare; United States

Topics: Aged; Allopurinol; Ethnicity; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Medicare; United States

Topics: Aged; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Medicare; United States

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Skin

Several observational studies reported that allopurinol, an effective treatment for gout, was associated with important reductions in cardiovascular (CV) events, with calls for large, randomized trials, although some results were conflicting. The present study was undertaken to assess the extent of time-related biases in these observational studies.. We searched the literature for all observational studies reporting on allopurinol and CV events, focusing on 2 time-related biases. Time-related confounding bias results from studies using cohorts of patients all exposed to allopurinol, with comparisons based on episodes of allopurinol discontinuation, where confounding factors are not updated over follow-up time. Immortal time bias arises from the exposure misclassification of periods of cohort follow-up during which the outcome under study cannot occur.. We identified 12 studies, of which 8 were affected by time-related confounding bias or immortal time bias, while the remaining 4 studies avoided these biases. The studies affected by time-related confounding bias resulted in significant reductions in the incidence of CV events with allopurinol use (pooled hazard ratio [HR] 0.88 [95% confidence interval (95% CI) 0.85-0.92]), as did the studies affected by immortal time bias (pooled HR 0.79 [95% CI 0.72-0.87]). The 4 studies that avoided these biases resulted in a pooled HR of 1.07 (95% CI 0.91-1.25).. Observational studies reporting significantly reduced incidence of CV events with allopurinol use were affected by time-related biases. Overall, studies that avoided these biases did not find a protective effect. The ALL-HEART randomized trial will provide important and accurate evidence on the potential effectiveness of allopurinol on CV outcomes.

Topics: Allopurinol; Bias; Cardiovascular Diseases; Gout; Gout Suppressants; Humans; Observational Studies as Topic

The quality of care for patients admitted with a primary diagnosis of gout, both before and after admission, has not been systematically examined.. To understand national trends in hospital admission for a primary diagnosis of gout in Aotearoa New Zealand over the past 10 years and the quality of care for gout received by these patients before and after the admission.. Data from the Aotearoa New Zealand National Collections from 1 January 2007 to 31 December 2019 were analysed to determine rates of hospital admission for a primary diagnosis of gout. Admission data include cost-weight analysis, as well as quality of care data including gout-specific medication dispensing in the year prior and year after admission.. There were 13 721 admissions with a primary diagnosis of gout over the analysis period, with an average cost per admission in 2019 of NZ$4301. The rate of admission per 100 000 population was highest in Pacific peoples followed by Māori. Although dispensing of any allopurinol increased in the year after admission, rates of regular allopurinol dispensing remained low; 38.1% for admissions in 2018. Patients who were younger (especially 20-44 years), not enrolled in a primary health organisation before admission and female had lower rate of regular allopurinol after admission.. In this nationwide study, rates of admission for gout were highest in Pacific peoples and in Māori. Rates of regular allopurinol dispensing were low even after admission for a primary diagnosis of gout. These findings highlight the need for improvements in gout management in Aotearoa New Zealand, including in post-discharge planning from secondary care inpatient services.

Topics: Aftercare; Allopurinol; Female; Gout; Gout Suppressants; Hospitals; Humans; New Zealand; Patient Discharge; Quality of Health Care

With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone.. Using the Korean National Health Insurance claims data (2002-17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05-1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43-1.93) among allopurinol initiators compared with benzbromarone.. In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.

Topics: Allopurinol; Benzbromarone; Cardiovascular Diseases; Cohort Studies; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Risk Factors

There has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout.. Individuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity.. 22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23-1.33), dementia (1.23, 1.11-1.35), and an outpatient visit for gout in the prior year (1.19, 1.09-1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone.. Allopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.

Topics: Allopurinol; Diabetes Mellitus; Female; Gout; Gout Suppressants; Humans; Retrospective Studies

Topics: Aged; Allopurinol; Cohort Studies; Female; Gout; Humans; Incidence; Middle Aged; Parkinson Disease; Retrospective Studies; Risk Factors

There are no sufficient data available on the use of febuxostat in patients undergoing dialysis.. To investigate the efficacy and tolerability of febuxostat in gout patients on dialysis.. We retrospectively reviewed clinical and laboratory data available from a referral centre from January 2012 to December 2018. We included gout patients who initiated febuxostat during dialysis. Data regarding serum uric acid levels before and after the febuxostat treatment and clinical information such as gout attack after febuxostat initiation, as well as adverse events involving febuxostat treatment, were obtained from medical records.. Among 62 patients who were treated with febuxostat for over 3 months, 45 were undergoing haemodialysis (HD) and 17 were undergoing peritoneal dialysis (PD). The mean serum uric acid level was significantly reduced 3 months after treatment (3.71 ± 1.32 mg/dL) compared with that at the pretreatment level (9.36 ± 2.06 mg/dL) (P < 0.001). The serum uric acid level was observed to be significantly reduced at 3 months in both HD and PD patients and subsequently remained at a significantly reduced level for 12 months. Of the 62 patients, only two stopped febuxostat due to its adverse effects. Initial dose of 80 mg/day was associated with higher adverse events compared to dose of 20-40 mg/day (odds ratio 8.25, 95% confidence interval 1.90-35.97, P = 0.006).. Febuxostat is efficacious and well tolerated in gout patients on dialysis. Febuxostat taken at dose of 20-40 mg/day might be appropriate initial dose in patients undergoing dialysis.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Dialysis; Retrospective Studies; Treatment Outcome; Uric Acid

Colchicine prophylaxis to prevent gout flares when commencing urate-lowering therapy is recommended by international rheumatology society guidelines. Whether this is a cost-effective intervention is currently unknown. Our objective was to perform a cost-effectiveness analysis using both a US cost input model and an Australian cost input model.. This cost-effectiveness analysis was completed from the point of view of the third-party payer. We used a 2-arm decision tree with 1 arm commencing allopurinol with no colchicine prophylaxis and the other with colchicine prophylaxis. Model inputs were drawn from published literature where available. We completed a univariate and probabilistic sensitivity analysis to confirm the robust nature of the modeling. The time frame for the model was 6 months.. The colchicine prophylaxis arm resulted in a cost of $1,276 and 0.49 quality-adjusted life-years (QALYs), while in the placebo arm the cost was $516 and 0.47 QALYs, with an incremental cost-effectiveness ratio of $34,004 per QALY gained. In Australia, where cost of colchicine was much lower, the colchicine arm dominated the placebo ($208 [Australian] in the colchicine arm versus $415 [Australian] in the placebo). Univariate and probability sensitivity analysis demonstrated that results were robust to changes in input parameters. In the probabilistic sensitivity analysis, the probability of colchicine prophylaxis being the most cost-effective option was 93% in the US and 100% in the Australian setting.. Colchicine prophylaxis to prevent gout flares while commencing allopurinol in gout is very cost-effective.

Topics: Allopurinol; Australia; Colchicine; Cost-Benefit Analysis; Disease Progression; Drug Costs; Gout; Gout Suppressants; Humans; Quality-Adjusted Life Years; Time Factors; Treatment Outcome; United States

The objectives of our study were to compare the efficacy of febuxostat with allopurinol in Thai subjects with gout, as well as to determine the predictive factors of responsiveness to urate-lowering agents and to evaluate the safety of febuxostat in a real-world setting.. The study was a retrospective cohort study; a total of 354 gout patients were recruited from February 2015 to November 2018. The patients were categorized according to prescription of allopurinol or febuxostat. Demographic data, comorbidities, concomitant medications, gout-related clinical parameters, and the laboratory results were collected. The serial serum urate (sUA) levels were recorded at the beginning of the treatment (baseline), and after treatment at 12 weeks, 18 weeks, and 27 weeks. The primary efficacy endpoint was the achievement of target urate of < 6 mg/dl in people taking febuxostat, compared with those taking allopurinol. The secondary endpoints were the predictive factors of achieving target urate level and adverse drug reactions in patients taking febuxostat. Multivariable regression analysis was used to determine factors associated with achieving target serum urate.. After the treatment, the febuxostat groups had significantly lower mean sUA compared with the allopurinol groups across all follow-up periods. The proportion of people who achieved target serum urate was also higher in the febuxostat groups compared with the allopurinol groups throughout the follow-up periods. The multivariable regression analysis showed that febuxostat 40 mg (OR = 10.96 (95% CI 4.32-27.80); p value < 0.001), febuxostat 80 mg (OR = 9.54 (95% CI 3.91-23.28), smoking (OR = 2.35 (95% CI 1.13-4.91); p value = 0.023), and low baseline serum urate (OR = 0.62 (95% CI 0.52-0.74); p value < 0.001) were associated with the achievement of target serum urate. No adverse drug reaction from febuxostat was observed even among people with renal insufficiency.. In a Thai cohort, people receiving febuxostat are more likely to achieve target serum urate level, compared with people receiving allopurinol. Febuxostat (40 or 80 mg), smoking, and low baseline serum urate were associated with the achievement of target serum urate.. • Febuxostat showed superior urate-lowering efficacy compared with allopurinol in an Asian population. • In addition to febuxostat, lower baseline serum urate level and history of smoking were associated with achieving target serum urate in gout patients.

Topics: Allopurinol; Cohort Studies; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Retrospective Studies; Thailand; Thiazoles; Treatment Outcome; Uric Acid

Gout is an important cause of disability among Filipinos, despite measures for effective management. This study aims to determine attainment of target serum uric acid level (SUA ≤ 6 mg/dl) among patients with gout given urate-lowering therapy (ULT) over 6-12 months.. This is a single-center, prospective cohort study conducted in one adult Arthritis Clinic at the University of the Philippines-Philippine General Hospital which included 138 patients with gout (1977 ACR criteria), SUA ≥ 6 mg/dl prior to ULT, initiated on ULT (allopurinol or febuxostat), with six months minimum follow-up and with SUA determination post-treatment.. Target SUA level was not achieved at 6 and 12 months of ULT in most of this cohort. This mirrors the deficient control of gout and should urge health professionals to fully study and address the problem.

Topics: Adult; Aged; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Philippines; Treatment Outcome; Uric Acid

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Asymptomatic Diseases; Case-Control Studies; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Taiwan; Treatment Failure; Young Adult

Determine the real-world incidence of acute gout prophylaxis (AGP) prescribing when a xanthine oxidase inhibitor (XOI) is initiated and describe characteristics of AGP prescribing.. Retrospective cohort analysis from 2007 to 2017 using medical and prescription claims from an administrative database (IQVIA™ Health Plan Claims Database) among adult patients with a diagnosis of gout. Primary endpoint was the proportion of patients receiving AGP among all patients newly initiated on XOI therapy. Secondary endpoints included incidence proportions of acute flare and of XOI discontinuation among patients who received AGP compared to those who did not. Chi-square and Fisher's exact tests were used in univariate analysis of proportions between treatment groups.. A total of 7414 patients were included for analysis. There were 697 patients (9.4%) who received AGP with XOI initiation and colchicine alone was the most common medication used among patients who received prophylaxis (n = 303, 43.4%). The incidence proportion of patients with an acute gout flare within 3 months of index was 21.5% in the AGP cohort and 12.7% in the no prophylaxis cohort (p < 0.001). The proportion of patients who discontinued XOI within 12 months of initiation was 38.7% in the AGP cohort and 46.2% in the no prophylaxis cohort (p < 0.001).. In the real world, the proportion of patients who receive AGP with initiation of XOI therapy is low and discontinuation of XOI within 12 months of initiation is significant. In this analysis, use of AGP was not associated with a lower risk of acute gout flare after initiation of XOI therapy. Key Points • Real-world acute gout prophylaxis (AGP) prescribing with xanthine oxidase inhibitor (XOI) initiation is very low despite current guideline recommendations • More than one third of patients discontinue XOIs within 12 months of initiation regardless of AGP prescribing.

Topics: Adult; Cohort Studies; Gout; Gout Suppressants; Humans; Retrospective Studies; Symptom Flare Up; Xanthine Oxidase

There has been growing interest in the use of xanthine oxidase (XO) as a therapeutic agent to prevent gout and hyperuricemia. In the present study, XO inhibitory peptides were identified from tuna protein by virtual screening, and molecular docking was used to elicit the interaction mechanism between XO and peptides.. A novel tetrapeptide, EEAK, exhibited high XO inhibitory activity with an IC. This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia. © 2020 Society of Chemical Industry.

Topics: Animals; Catalytic Domain; Enzyme Inhibitors; Fish Proteins; Gout; Humans; Hydrogen Bonding; Hyperuricemia; Kinetics; Molecular Docking Simulation; Peptides; Tuna; Xanthine Oxidase

Topics: Benzbromarone; Bone Resorption; Enzyme Inhibitors; Gout; Humans; Male; Metatarsal Bones; Metatarsophalangeal Joint; Middle Aged; Nitriles; Osteogenesis; Osteophyte; Pyridines; Treatment Outcome; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Topics: Allopurinol; Diabetes Mellitus, Type 1; Gout; Gout Suppressants; Humans; Kidney; Uric Acid

To assess rheumatologists' views and practices related to shared decision-making (SDM) in gout treatment. We performed a cross-sectional electronic survey of rheumatologists at U.S. Veterans Affairs (VA) medical centers, assessing views and practices related to SDM in gout. Of the 154 VA rheumatology providers eligible, 90 responded (response rate, 58%). Fifty-eight percent were female, the mean age was 51 years (standard deviation, 9.6), 42% had > 20 years of experience in medical practice. Rheumatologists reported routinely offering a choice to their patients for (1) starting urate-lowering therapy (ULT) for gout vs. doing nothing (70%); (2) choosing NSAIDs, corticosteroids, or colchicine for the treatment of acute flares (67%); and (3) choosing NSAIDs, corticosteroids, or colchicine for anti-inflammatory prophylaxis when starting ULT (51%). Very few rheumatologists offered choice regarding (4) choosing allopurinol vs. febuxostat as the first ULT (16%) and (5) taking daily ULT long-term vs. intermittently (15%). Rheumatologists perceived that a large proportion of patients were often or sometimes unsure of the best choice for these five decisions, 34%, 76%, 76%, 52%, and 54%, respectively. Similar proportions of rheumatologists felt that patients were uninformed about both medication benefits and risks, unclear about the personal importance of the benefits and risks, and unsupported in decision-making. For the five decisions respectively, rheumatologists supported SDM with patients in 76%, 56%, 58%, 27%, and 25%. The majority of VA rheumatologists incorporated SDM in several gout treatment decisions. Rheumatologists also recognized that patients need better support to participate in SDM in gout. Key Points: • Rheumatologists offered shared decision-making to gout patients for 3 key treatment decisions. • Rheumatologists perceived that many patients were unsure of the best choice for these decisions. • Rheumatologists felt that patients were uninformed about medication benefits/risks and unsupported in decision-making.

Topics: Allopurinol; Cross-Sectional Studies; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Rheumatology

Topics: Allopurinol; Cardiovascular Diseases; Cause of Death; Drug Labeling; Febuxostat; Gout; Gout Suppressants; Humans; Mortality; Polyethylene Glycols; Practice Patterns, Physicians'; Probenecid; Risk Factors; Thioglycolates; Triazoles; United States; United States Food and Drug Administration; Urate Oxidase

Topics: Allopurinol; Drug Tapering; Gout; Gout Suppressants; Humans; Hyperuricemia; Symptom Flare Up

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Prospective Studies

The Bayesian decision-analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric-based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision-theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.

Topics: Allopurinol; Bayes Theorem; Clinical Trials, Phase III as Topic; Computer Simulation; Decision Theory; Drug Development; Economics, Pharmaceutical; Febuxostat; Gout; Humans; Hyperuricemia; Investments; Models, Biological; Models, Economic; Reimbursement Mechanisms; Research Design; Sample Size; Uncertainty; Uric Acid

Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3

Topics: Allopurinol; Cardiovascular Diseases; Endothelial Cells; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Risk Factors; Uric Acid

Allopurinol-related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA-B*58:01, the allele frequency (AF) of which is largely different among East Asians. However, evidence of population differences in SCAR development and relevance of genetic and/or other risk factors in the real-world remain unelucidated. This study aimed to evaluate population differences in allopurinol-related SCAR incidence related to genetic and/or other risk factors among East Asians in the real-world. A population-based cohort study was conducted using claims databases from Taiwan, Korea, and Japan. New users of allopurinol (311,846; 868,221; and 18,052 in Taiwan, Korea, and Japan, respectively) were followed up to 1 year. As control drugs, phenytoin and carbamazepine were used. The crude incidence rate ratios (IRRs) of SCARs for allopurinol against phenytoin or carbamazepine were the highest in Taiwan (IRR, 0.62 and 1.22; 95% confidence interval [CI], 0.54-0.72 and 1.01-1.47, respectively), followed by Korea (IRR, 0.34 and 0.82; 95% CI, 0.29-0.40 and 0.77-0.87), and the lowest in Japan (IRR, 0.04 and 0.16; 95% CI, 0.02-0.08 and 0.09-0.29). This order was accordant with that of AF ratios (AFRs) reported of HLA-B*58:01 against alleles responsible for phenytoin- or carbamazepine-related SCARs. The IRRs were higher in patients with chronic kidney disease, females, and elderly. This study demonstrated population differences in the risk of allopurinol-related SCAR development among East Asians based on genetic and other common risk factors. This finding will help to promote appropriate risk management for allopurinol-related SCARs based on ethnic origins. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC? Allopurinol-related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA-B*58:01, the allele frequency of which is largely different among East Asians. However, there is no direct real-world evidence of population differences in SCAR development and the influence of genetic factors and/or other risk factors. WHAT QUESTION DID THIS STUDY ADDRESS? Do population differences in development of allopurinol-related SCARs, depending on genetic factors and/or other risk factors, exist among three East Asians in the real-world? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The current analysis, based on comparisons of relative risks of SCAR incidence, provides real-world evidence of population differences in allopurinol-related SCAR develo

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Asian People; Child; Child, Preschool; Drug Eruptions; Female; Follow-Up Studies; Gene Frequency; Genetic Predisposition to Disease; Gout; Gout Suppressants; HLA-B Antigens; Humans; Incidence; Infant; Infant, Newborn; Japan; Male; Middle Aged; Republic of Korea; Retrospective Studies; Risk Factors; Severity of Illness Index; Taiwan; Young Adult

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans

There is scant data on the role of hyperuricaemia, gout and allopurinol treatment in chronic kidney disease (CKD). Therefore, our aim is to investigate the possible associations between hyperuricaemia, gout, prescription of allopurinol and renal outcomes in patients with CKD.. The retrospective cohort study involved 1123 Royal Brisbane and Women's Hospital (RBWH) patients, enrolled in the CKD.QLD registry from May 2011 to August 2017. Patients were divided into two uric acid categories, with uric acid ≤ 0.36 mmol/L and > 0.36 mmol/L. Association of delta estimated glomerular filtration rate (eGFR) with gout, allopurinol treatment and hyperuricaemia were analysed.. Patients with an entry urate > 0.36 mmol/L were older, had higher body mass index (BMI) and worse baseline kidney function. Proportion of patients with gout, hyperuricaemia and allopurinol treatment increased with advanced CKD stages. Age-adjusted analysis revealed a significant association between serum urate level and delta eGFR, with no significant association between gout, treatment with allopurinol and delta eGFR. Furthermore, neither gout nor the prescription of allopurinol had a significant effect on the time to renal death (composite end point of kidney replacement therapy or death).. Hyperuricaemia seemed to be independently associated with faster CKD progression or renal death. This was not observed with gout or prescription of allopurinol. Furthermore, allopurinol was not associated with decreased incidence of cardiovascular events. These data suggest that hyperuricaemia is likely the effect and not the cause of CKD or CKD progression.

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Queensland; Registries; Renal Insufficiency, Chronic; Retrospective Studies

Topics: Aged; Allopurinol; Cardiovascular Diseases; Febuxostat; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Retrospective Studies; Risk Assessment; Survival Rate; United States

The objective of this study was to compare the prophylactic effect of regular-dose (RD, 1.2 mg/day) vs low-dose (LD, 0.6 mg/day) colchicine on gout flare when initiating urate-lowering therapy.. In this retrospective cohort study, we included gout patients who were initiated on either allopurinol or febuxostat, in combination with colchicine therapy and followed them up for 3 months. We analysed the rates of gout flare and adverse events according to the dose of colchicine. We performed the inverse probability of treatment weighting (IPTW) and weighted logistic regression analysis to assess the treatment effect. Analysis of gout flares and adverse events was performed on an intention-to-treat (ITT) and per-protocol (PP) basis.. Of the total of 419 patients with gout, 177 patients (42.2%) received LD colchicine, whereas 242 patients (57.8%) received RD colchicine. Lower BMI and estimated glomerular filtration rate, and higher incidence of cardiovascular disease were seen in the LD group than in the RD group. In IPTW-adjusted analysis, events of gout flare were not significantly different between the LD and RD groups [ITT: 14.3% vs 11.3%; odds ratio (OR): 1.309, 95% CI: 0.668, 2.566, P = 0.432; PP: 15.3% vs 10.0%; OR: 1.623, 95% CI: 0.765, 3.443, P = 0.207]. However, LD colchicine was associated with a lower rate of adverse events than RD colchicine [ITT: 8.2% vs 17.9%; OR: 0.410, 95% CI: 0.217, 0.777; P < 0.05; PP: 8.4% vs 17.2%; OR: 0.442, 95% CI: 0.223, 0.878; P < 0.05].. Our data suggest that LD colchicine can adequately prevent gout flare with fewer adverse events compared with RD colchicine.

Topics: Adult; Aged; Allopurinol; Cohort Studies; Colchicine; Drug Therapy, Combination; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Symptom Flare Up

Topics: Allopurinol; Benzbromarone; Febuxostat; Gout; Gout Suppressants; Humans; Solubility; Uric Acid

The treatment of gout is subject to different national and international guidelines. These guidelines differ in the extent to which they consider cardiovascular risk factors when deciding to start allopurinol. Observational studies and limited trial data suggest that treatment with allopurinol may reduce the risk of cardiovascular events in patients with gout. However, at this moment allopurinol remains an unproven strategy. There is need for a large randomized placebo-controlled trial with sufficient power and duration of follow-up.

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Female; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Male; Risk Factors

In the present study, in silico predictions and molecular docking were performed on five clerodane diterpenes (1-5) from Polyalthia longifolia seeds to evaluate their potential as xanthine oxidase (XO) inhibitors. The initial screening was conducted by target prediction using TargetNet web server application and only compounds 3 and 4 showed a potential interaction with XO. Compounds 3 and 4 were subsequently subjected to in silico analyses on XO protein structure (PDB: 1N5X) using Schrödinger Release 2020-3 followed by structural modeling & molecular simulation studies to confirm the initial prediction result and identify the binding mode of these compounds to the XO. Molecular docking results revealed that compounds 3 (-37.3 kcal/mol) and 4 (-32.0 kcal/mol) binds more stably to XO than the reference drug allopurinol (-27.0 kcal/mol). Interestingly, two residues Glu 802 and Thr 1010 were observed as the two main H-bond binding sites for both tested compounds and the allopurinol. The center scaffold of allopurinol was positioned by some π-π stacking with Phe 914 and Phe 1009, while that of compounds 3 and 4 were supported by many hydrophobic interactions mainly with Leu 648, Phe 649, Phe 1013, and Leu 1014. Additionally, the docking simulation predicted that the inhibitory effect of compounds 3 and 4 was mediated by creating H-bond with particularly Glu 802, which is a key amino acid for XO enzyme inhibition. Altogether, in vitro studies showed that compounds 3 and 4 had better inhibitory capacity against XO enzyme with IC50 values significantly (p < 0.001) lower than that of allopurinol. In short, the present study identified cleroda-4(18),13-dien-15,16-olide as novel potential XO inhibitors, which can be potentially used for the treatment of gout.

Topics: Diterpenes, Clerodane; Enzyme Assays; Gout; Humans; Molecular Docking Simulation; Plant Extracts; Polyalthia; Seeds; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Gout; Gout Suppressants; Humans

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.

Topics: Animals; Benzimidazoles; Benzoxazoles; Cell Line; Disease Models, Animal; Gout; Humans; Hyperuricemia; Interleukin-1beta; Liver; Mice; Monocytes; NLR Family, Pyrin Domain-Containing 3 Protein; Oxonic Acid; Rats; Structure-Activity Relationship; Synovial Membrane; Uric Acid; Xanthine Oxidase

To assess factors associated with the ability to achieve and maintain target serum urate (SU) with allopurinol in patients with gout.. We used US Veterans Affairs (VA) databases from 2002-2012. Eligible patients had ≥ 1 inpatient or ≥ 2 outpatient visits with a diagnostic code for gout, filled a new index allopurinol prescription, had at least 1 posttreatment SU level measured, and met the 12-month observability rule. Treatment successes were defined as the achievement of postindex SU < 6 mg/dl (success 1) and postindex SU < 6 mg/dl that was sustained (success 2).. Of the 198,839 unique patients with allopurinol use, 41,153 unique patients (with 47,072 episodes) and 17,402 unique patients (with 18,323 episodes) were eligible for analyses for success 1 and success 2; 42% each achieved (success 1) or achieved and maintained postindex SU < 6 mg/dl (success 2). In multivariable-adjusted models, factors associated with significantly higher odds of both outcomes were older age, normal body mass index, Deyo-Charlson index score of 0, rheumatologist as the main provider rather than non-rheumatologist, midwestern US location for the healthcare facility, a lower hospital bed size, military service connection for medical conditions of 50% or more (a measure of healthcare access priority), longer distance to the nearest VA facility, and lower preindex SU.. We identified novel factors associated with maintaining SU < 6 mg/dl based on a theoretical model. Several potentially modifiable factors can be targeted by individual/provider/systems interventions for improving successful achievement and maintenance of target SU in patients with gout.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Female; Follow-Up Studies; Gout; Gout Suppressants; Health Services Accessibility; Humans; Male; Middle Aged; Risk Factors; Severity of Illness Index; Treatment Outcome; United States; Uric Acid; Veterans

To describe trends in acute hospital admissions due to gout in England, with rheumatoid arthritis (RA) as a comparator, alongside prescribing trends for common gout medications.. An ecological study was performed using UK National Health Service (NHS) Digital Hospital Episode Statistics data to calculate the incidence of unplanned admissions with primary diagnoses of gout or RA in adults in England between April 2006 and March 2017. NHS Digital Community Prescription data for allopurinol, febuxostat, and colchicine were considered over a similar period.. The incidence of unplanned gout admissions increased by 58.4% over the study period, from 7.9 admissions per 100,000 population in 2006/07 to 12.5 admissions per 100,000 population in 2016/17 (p < 0.0001). Gout admissions increased as a proportion of all hospital admissions, and accounted for 349,768 bed-days cumulatively. Unplanned RA admissions halved over the study period, from 8.6 admissions per 100,000 population in 2006/07 to 4.3 admissions per 100,000 population in 2016/17 (p < 0.0001). Community prescriptions dispensed for allopurinol and colchicine have increased by 71.4% and 165.6%, respectively, since 2006 (p < 0.0001). Febuxostat prescriptions have increased 20-fold since 2010 (p < 0.0001), when prescription data became available.. Acute gout admissions in England increased between 2006 and 2017, accompanied by increasing prescription of gout therapies. Acute admissions due to RA halved over the same time period. These data call for aggressive target-driven therapy for this highly treatable disease.

Topics: Adult; Allopurinol; Febuxostat; Gout; Gout Suppressants; Hospitals; Humans; Incidence; State Medicine

Topics: Acromioclavicular Joint; Aged; Allopurinol; Female; Fluorodeoxyglucose F18; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Neck Pain; Paresthesia; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Shoulder; Single Photon Emission Computed Tomography Computed Tomography; Spondylarthritis; Zygapophyseal Joint

Topics: Adult; Allopurinol; Cardiovascular Diseases; Cause of Death; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Withholding Treatment

Gout has significant impact on the quality of life with over-utilisation of health resources. While lowering serum urate (SU) to ≤ 360 µmol/L improves clinical outcomes, this is usually not achieved. We describe the burden of gout and determine predictors of achieving SU target in gout patients in Singapore. This was a cross-sectional study of 282 gout patients from a Singapore hospital rheumatology service. Sociodemographic and lifestyle factors, co-existing medical conditions and medications, gout history and severity, SU levels and treatment were obtained. Patients with SU ≤ 360 µmol/L were compared with those > 360 µmol/L to determine factors associated with achieving SU target. Descriptive statistics and multivariate model were used. Severe disease was reported in 50%, with emergency attendances and hospitalisations in 33% and 19% respectively, and unemployment in 32%. Only 22% were at SU target and 67% on urate-lowering therapy (ULT) at recruitment. Hypertension, dyslipidaemia, chronic kidney disease and diabetes were prevalent in 56.7%, 48.2%, 32.3% and 18.8%, respectively. Malays had more comorbidities compared to Chinese participants. In multivariate analysis, ULT prescription and ≥ 2 comorbidities were associated with reaching SU target with odds ratios of 3.92 [95% confidence interval (CI) (1.75-8.71)] and 2.65 [95% CI (1.59-4.43)] respectively, independent of age, tophi, disease duration, body mass index, alcohol and diuretic use. Patients with gout have high disease burden resulting in significant healthcare utilisation. SU control is sub-optimal hence the use of ULT remains key in achieving SU target. Patients with other comorbidities are more likely to reach target than those with only gout as a single diagnosis.

Topics: Adult; Aged; Allopurinol; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dyslipidemias; Emergency Service, Hospital; Ethnicity; Febuxostat; Female; Gout; Gout Suppressants; Hospitalization; Humans; Hypertension; Hyperuricemia; Male; Middle Aged; Probenecid; Renal Insufficiency, Chronic; Severity of Illness Index; Singapore; Treatment Outcome; Uric Acid

Topics: Allopurinol; Cardiovascular System; Gout; Gout Suppressants; Humans; Hypertension

The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat.. This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use.. Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001).. In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.

Topics: Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Heart Disease Risk Factors; Humans; Male; Middle Aged; Retrospective Studies; Xanthine Oxidase

Pharmacological treatment and follow-up of gout is often inadequate.The patients risk repeated, painful arthritis flares and some develop chronic tophaceous gout and joint damage.. Since 1 March 2017, a structured care pathway has been established for patients with gout at the Department of Rheumatology, Haukeland University Hospital. Patients were placed on preventive medication, the majority on allopurinol, and were regularly monitored. Patient education is key to the care pathway. The treatment goal is to lower the concentration of serum urate to a level below a defined threshold value (360 µmol/l for non-tophaceous gout or 300 µmol/l for tophaceous gout). Patient data were collected on a continuous basis and recorded in a research database. The care pathway is assessed after 18 months.. A total of 103 patients have been included, of whom 93 (90 %) are men, with an average age of 63 years and large variations in duration of the disease (min.-max. 0-36 years). Eight patients left the care pathway during the project. The average level of serum urate at inclusion was 446 µmol/l (min.-max. 144-751 µmol/l). The average maximum dose of allopurinol was 333 mg (min.-max. 100-700 mg). Survival analysis showed that three months after the start of urate-lowering therapy, 49 % of the patients had achieved their analytical treatment goal. Altogether 83 % achieved the goal within six months. The majority (70 %) were free of flares after achieving the treatment goal.. A standardised care pathway for gout enables adaptation of preventive treatment through regular monitoring. The care pathway helps the vast majority of patients to achieve treatment goals, which is crucial to avoid arthritis flares.

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Care; Uric Acid

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Uric Acid; Veterans

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Morbidity

Topics: Aged; Aged, 80 and over; Allopurinol; Cost-Benefit Analysis; Female; Genetic Testing; Genotype; Gout; Gout Suppressants; HLA-B Antigens; Humans; Male; Middle Aged; Renal Insufficiency, Chronic

Topics: Aged; Allopurinol; Atrial Fibrillation; Febuxostat; Gout; Gout Suppressants; Humans; Medicare; United States

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

Topics: Allopurinol; Animal Structures; Animals; Chickens; Crystallization; Diet, High-Protein; Disease Models, Animal; Gout; Hyperuricemia; Kidney; Liver; Probenecid; Synovial Fluid; Uric Acid

The present study was designed to evaluate the xanthine oxidase (XO) inhibitory and antioxidant activities of 30 bioactive compounds present in edible food plants for the possible treatment of hyperuricemia.. The XO inhibitory, SO and DPPH radical scavenging activities of selected dietary polyphenols were determined by using colorimetric assays. The molecular docking analysis was performed to evaluate the insight into inhibitory mode of action of bioactive compounds against XO.. The results show that apigenin, galangin, kaempferol, quercetin, genistein and resveratrol potently inhibit XO enzyme among all tested compounds. Flavonoids exhibit higher, anthocyanins and hydroxycinnamic acids moderate, maslinic acid, ellagic acid, salicylic acid, [6]-gingerol and flavan-3-ols showed weak XO inhibitory activity. The results of molecular docking study revealed that these bioactive compounds bind with the active site of XO and occupy the active site which further prevents the entrance of substrate and results in the inhibition of XO.. Inhibition of XO gives a robust biochemical basis for management of hyperuricemia, gout and other associated diseases via controlling uric acid synthesis.

Topics: Acids, Carbocyclic; Antioxidants; Drug Evaluation, Preclinical; Enzyme Inhibitors; Flavonoids; Glycosides; Gout; Humans; Hyperuricemia; In Vitro Techniques; Molecular Docking Simulation; Phenols; Phytochemicals; Plant Extracts; Plants, Edible; Pyrans; Structure-Activity Relationship; Superoxides; Xanthine Oxidase

To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.. Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.. Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.. Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Rheumatology; United States

To assess the modalities and current practices in gout management reported by Moroccan rheumatologists. We performed a cross-sectional online survey using a questionnaire e-mailed to 360 rheumatologists included 30 multiple-choice questions. 105 rheumatologists responded to the survey with 29% of response rate. The number of gout patients seen per month was five (3-9); they were referred in 58.7% by a general practitioner. The clinical presentation of gout patients was dominated by gout crisis in 71%, and the association gout crisis and gouty arthropathy accounted for 19% of severe forms. 40% of rheumatologists apply the 2015ACR/EULAR classification criteria. Obesity accounted for 85.7% of the associated comorbidities. The most commonly prescribed Urate-lowering therapy (ULT) was allopurinol in 81.3% (± 12). 48% of rheumatologists reported starting allopurinol at 200 mg daily and associated it with colchicine during the first 6 months by 33.3%. The determination of uric acid levels was monitoring in 76.2% every 3 months. Administration of ULT to asymptomatic hyperuricemia was found in 69.5% when patients had renal complications, while only 14.3% recommended dietary and lifestyle measures. The median duration for therapeutic education was 15 min (10, 20). In 96.2%, the education of the patient was done orally. 93.3% of rheumatologists inform their patients on how to manage a gout attack, and 96.2% on the measures of hygiene and diet has adopted. Our survey gives an insight into the elements that should be improved in the management of gout by the Moroccan rheumatologists. It highlights the need to standardize the management of gout, hence the importance of developing Moroccan recommendations on gout.

Topics: Allopurinol; Colchicine; Cross-Sectional Studies; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Male; Morocco; Practice Patterns, Physicians'; Rheumatology; Surveys and Questionnaires; Uric Acid

Lifelong urate-lowering therapy (ULT) with xanthine oxidase inhibitors (XOIs), such as allopurinol and febuxostat, is the cornerstone of gout treatment. This study aimed to compare drug persistence between allopurinol and febuxostat as first-line ULT in patients with gout in real practice.. In this retrospective cohort study, we evaluated 602 patients with gout in whom allopurinol or febuxostat was newly initiated from December 2011 to November 2018 at a tertiary rheumatology centre. Persistence was defined as the duration from the first description date to the end of treatment with XOIs or the end of the study period (November 2019).. Among the 602 gout patients, the mean age was 60.2 years and 234 (38.9%) patients had tophi. Allopurinol and febuxostat were started in 237 (39.3%) and 365 (60.6%) patients, respectively. During the study period, 282 (46.8%) patients stopped taking XOIs, and the most common reason for XOI withdrawal was poor health literacy (61.3%). The 1- and 5-year persistence rates of XOIs were 67.2% and 40.9%, respectively. In the Kaplan-Meier analysis, persistence rates of allopurinol were significantly lower than those of febuxostat (p < 0.001). In the multivariable Cox regression model, allopurinol use was a significant risk factor for discontinuation of XOIs (HR = 2.01, p < 0.001). In addition, the presence of tophi and symptom duration < 24 months was independently associated with a higher risk of XOI withdrawal.. Long-term persistence of XOIs was suboptimal, and allopurinol had worse persistence rates than febuxostat among patients with gout. Key Points • Long-term persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) among patients with gout was suboptimal, and the major reason for XOI discontinuation was poor health literacy in our study. • We demonstrated that allopurinol had worse persistence rates than febuxostat among patients with gout, suggesting that febuxostat is a better option for long-term ULT in light of medication adherence in a real-world setting. • Patients with gout with tophi and shorter symptom duration were found to be at high risk for poor persistence of XOIs.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Middle Aged; Retrospective Studies; Uric Acid

Topics: Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration

Urate-lowering therapy (ULT) is effective in gout, but suboptimal management with wide variability in dose escalation remains widespread. We protocolized dose escalation of ULT to improve gout management. The aim was to reduce time to achieve target serum urate (SU) <360 µmol/L.. Process improvement tools were used to identify underlying causes of prolonged time to target SU. We designed a nurse-led telemedicine intervention for dose escalation of ULT. Patients with gout with SU ≥360 µmol/L meeting indications for ULT at a single institution were recruited. Exclusion criteria were estimated glomerular filtration rate <30 mL/min, pregnancy, cognitive impairment and poor mobility. A nurse-led telemedicine clinic was set up to perform patient education, monitoring of adverse events and drug escalation. We partnered with primary healthcare centers for routine blood tests.. From July 2016 to December 2017, 127 patients were recruited. Median time to target SU was 19.0 weeks (interquartile range [IQR] 11.0-31.0). Median dose of allopurinol was 300 mg/d (IQR 200-400) in normal renal function and lower in renal impairment. Median telemedicine calls required to achieve target SU was 2 (IQR 1-3). No patient was hospitalized for gout flares. Two patients had adverse drug reactions, one required cessation of allopurinol for rash with eosinophilia, the other had self-resolving ulcers and allopurinol was continued. Lower baseline SU and number of gout flares were associated with attainment of target SU.. A nurse-led telemedicine for gout care is effective and safe. Our results affirm the utility of telemedicine in increasing access to care and lower healthcare utilization.

Topics: Adult; Aged; Allopurinol; Biomarkers; Down-Regulation; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Nurse's Role; Patient Care Team; Program Evaluation; Proof of Concept Study; Rheumatologists; Rheumatology; Telemedicine; Time Factors; Treatment Outcome; Uric Acid

The aim of this study was to investigate whether there are blood glucose fluctuations in gout patients with hyperuricemia and normal glucose tolerance, and the effect of urate-lowering therapy on blood glucose fluctuations.. Thirty patients with newly diagnosed gout, hyperuricemia and normal glucose tolerance were enrolled in our study. Continuous glucose monitoring system (CGMS) was used to detect the blood glucose fluctuations of these gout patients. Changes in blood glucose fluctuations after allopurinol therapy were also evaluated.. Compared with the reference values of blood glucose fluctuation parameters in China, gout patients had greater glycemic fluctuations including higher mean amplitude of glucose excursions (MAGE) (4.65 vs 1.94 mmol/L, P < .001), higher largest amplitude of blood glucose excursions (LAGE) (4.99 vs 3.72 mmol/L, P < .001) and higher standard deviations of blood glucose (SDBG) (1.36 vs 0.79 mmol/L, P < .001). MAGE was significantly correlated with uric acid (β = .007, P = .024) and HOMA-insulin resistance (IR) (β = .508, P = .03). Allopurinol treatment significantly reduced MAGE (4.16 vs 4.65 mmol/L, P < .001), SDBG (0.99 vs 1.36 mmol/L, P < .001) and HOMA-IR (2.26 vs 3.01, P < .001) in gout patients.. Blood glucose fluctuation increased even in the stage of normal glucose tolerance among gout patients. Blood glucose fluctuations in gout patients were associated with the level of serum uric acid and allopurinol could decrease blood glucose fluctuation as well as IR.

Topics: Adult; Aged; Allopurinol; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Down-Regulation; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Insulin Resistance; Male; Middle Aged; Predictive Value of Tests; Time Factors; Treatment Outcome; Uric Acid; Young Adult

Topics: Animals; Anti-Inflammatory Agents; Edema; Gout; Gout Suppressants; Humans; Hyperuricemia; Mice; Mice, Nude; Oryza; Peptides; Plant Extracts; Uric Acid; Xanthine Oxidase

Although studies have demonstrated the association of hyperuricemia with cardiovascular (CV) diseases, few have explored the effect of urate-lowering therapy (ULT) on the incidence of CV diseases. Therefore, we compared the risks of hospitalized coronary artery disease (CAD), stroke, heart failure (HF), and all-cause mortality between ULT users and nonusers among patients with gout.. We performed this retrospective cohort study using Taiwan's population-based National Health Insurance Research Database. In total, 5218 patients with gout were included from 2000 to 2012. We compared the incidence rates (IRs) of hospitalized CAD, stroke, HF, and all-cause mortality between ULT users and matched nonusers.. The IRs of hospitalized stroke were 0.6 and 1.0 per 100 person-years for ULT users and nonusers, respectively, after adjusting for age, sex, residence, comorbidities, and medications. ULT users showed lower adjusted hazard ratios (aHR) for hospitalized stroke (aHR: 0.52, p < 0.001) and all-cause mortality (aHR: 0.6, p = 0.02) than nonusers. Subgroup analyses revealed that uricosuric agents and xanthine oxidase inhibitors were significantly associated with lower risks of hospitalized stroke and all-cause mortality, respectively. The effect of uricosuric agents on the decrease in hospitalized stroke risk indicated a dose-response relationship.. Our study showed lower risks of hospitalized stroke and all-cause mortality in ULT users than in nonusers among patients with gout. Therefore, patients with gout may receive ULT to mitigate the risks of hospitalized stroke and mortality.

Topics: Adult; Aged; Allopurinol; Female; Gout; Gout Suppressants; Hospital Mortality; Hospitalization; Humans; Hyperuricemia; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Risk Assessment; Stroke; Taiwan; Treatment Outcome; Uric Acid; Young Adult

Currently, only two drugs for reducing uric acid (UA), allopurinol and febuxostat, are registered in the Russian Federation, but their use does not allow to achieve the target level of UA in all cases. According to the results of numerous randomized trials, hyperuricemia and gout are associated with the corresponding components of the metabolic syndrome, including diabetes mellitus. The influence of factors is due to the need to search for new drugs that have a complex effect on several components of metabolic syndrome at once. Potentially attractive in this regard is a new group of drugs for the treatment of type 2 diabetes mellitus inhibitors of the sodium-glucose cotransporter of type 2, which, in addition to the main hypoglycemic actions, showed positive effects on the cardiovascular system, kidneys, as well as lowering UA.. В настоящее время в Российской Федерации зарегистрировано только два препарата для снижения мочевой кислоты (МК) аллопуринол и фебуксостат, однако их использование позволяет достичь целевого уровня МК не во всех случаях. Согласно результатам многочисленных рандомизированных исследований гиперурикемия и подагра ассоциированы со многими компонентами метаболического синдрома, включая сахарный диабет. Указанные факторы диктуют необходимость поиска новых препаратов, оказывающих комплексное влияние сразу на несколько компонентов метаболического синдрома. Потенциально привлекательной в этом плане является новая группа препаратов для лечения сахарного диабета 2-го типа ингибиторы натрий-глюкозного котранспортера 2-го типа, которые помимо основного сахароснижающего действия показали положительные эффекты в отношении сердечно-сосудистой системы, почек, а также снижения уровня МК.

Topics: Allopurinol; Diabetes Mellitus, Type 2; Gout; Gout Suppressants; Humans; Hyperuricemia; Russia; Sodium-Glucose Transport Proteins

Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.. Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.. Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.. Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Inflammation

Singh JA, Cleveland JD.

Topics: Aged; Allopurinol; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Medicare; United States

To determine the feasibility and validity of using wearable activity trackers to test associations between gout flares with physical activity and sleep.. Participants with physician-diagnosed gout, hyperuricemia (≥ 6.8 mg/dl), current smartphone use, and ≥ 2 self-reported flares in the previous 6 months were enrolled. Physical activity, heart rate, and sleep data were obtained from wearable activity trackers (Fitbit Charge HR2). Daily compliance was defined by the availability of sufficiently complete activity data at least 80% of the day. Associations of weekly gout flares with sleep and activity were measured by comparing flare-related values to average sleep and steps per day. We used mixed linear models to account for repeated observations.. Forty-four participants enrolled; 33 met the criteria for minimal wear time and flare reporting, with activity tracker data available for 60.5% of all total study days. Mean ± SD age was 48.8 ± 14.9 years; 85% were men; 15% were black; 88% were on allopurinol or febuxostat, and 30% reported ≥ 6 flares in the prior 6 months. Activity trackers captured 204 (38%) person-weeks with flares and 340 (62%) person-weeks without flares. Mean ± SD daily step count was significantly lower (p < 0.0001) during weeks with gout flares (5900 ± 4071) than during non-flare periods (6972 ± 5214); sleep however did not differ.. The pattern of wear in this study illustrates reasonable feasibility of using such devices in future arthritis research. The use of these devices to passively measure changes in physical activity patterns may provide an estimate of gout flare occurrence and duration.. NCT, NCT02855437 . Registered 4 August 2016.

Topics: Adult; Allopurinol; Exercise; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Symptom Flare Up; Wearable Electronic Devices

To investigate the existence of distinct classes of gout flare trajectories and compare their gout-specific, comorbid, and sociodemographic characteristics.. In a prospective cohort study, adults with gout who were registered with 20 general practices self-reported the number of gout flares experienced at baseline and after 6, 12, 24, and 36 months via postal questionnaires. Latent class growth analysis (LCGA) was used to identify distinct gout flare trajectory classes. Statistical criteria and clinical interpretability were used to decide the optimal number of classes. Baseline comorbidities, medications, and sociodemographic and gout-specific characteristics of members of each class were described.. A total of 1,164 participants (mean ± SD age 65.6 ± 12.5 years; 972 [84%] male) were included. Six latent gout flare trajectory classes were identified: "frequent and persistent" (n = 95), "gradually worsening" (n = 276), "frequent then improving" (n = 14), "moderately frequent" (n = 287), "moderately frequent then improving" (n = 143), and "infrequent" (n = 349). The "frequent and persistent" trajectory had the most class members classified as obese and, along with the "gradually worsening" class, the highest proportion who were socioeconomically deprived. The "frequent and persistent," "gradually worsening," and "frequent then improving" classes had the highest proportions of class members with an estimated glomerular filtration rate <60 ml/minute/1.73 m. Six distinct gout flare trajectories were identified. Infrequent flares were associated with allopurinol use and lower serum urate levels, supporting the use of urate-lowering therapy to reduce flare frequency. The characteristics of flare trajectory classes could help to target interventions and improve patient care.

Topics: Aged; Allopurinol; Disease Progression; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Primary Health Care; Symptom Flare Up; Uric Acid

Difficulties and errors in the treatment of patients with the gout arise, mainly, during urate-lowering therapy. The article discusses possible medical errors in acute gouty arthritis and during chronic tophaceous gout in the light of the updated international recommendations of the American College of Rheumatology (ACR) and the European Antirheumatic League (EULAR 2018). As an example of inadequate treatment, the authors describe a case of a patient with chronic tophaceous gout. Errors in the diagnosis and treatment of the patient caused various complications and unjustified surgical intervention - amputation of the right finger and removal of a large tophus in the left forearm. Based on the analysis of mistakes made in the diagnosis and treatment of gout, the authors propose an algorithm for therapeutic tactics in different periods of the disease. So, for the relief of exacerbation in acute gouty arthritis, it is recommended to take the following drugs at starting doses: colchicine at a dose of 1.8 mg/day (1.2 mg immediately followed by 0.6 mg 1 hour later during 7-10 days or until complete relief of the gout attack), non-steroidal anti-inflammatory drugs (nimesulide up to 200 mg/day) or glucocorticosteroids (prednisolone at a dose of 30 mg/day for 3-5 days with subsequent withdrawal). The first-line urate-lowering drugs for chronic tofaceous gout are xanthine oxidase inhibitors - allopurinol and febuxostat. Allopurinol is prescribed no earlier than 2 weeks after the arthritis attack has stopped at a starting dose of no more than 100 mg/day, the dose is gradually increased to the minimum effective. The starting dose of febuxostat is 40 mg/day. Also, together with allopurinol or febuxostat, it is recommended to take uricosuric drugs (probenecid 500 mg/day or benzbromarone 50-200 mg/day). At the same time, the authors draw attention to the inadmissibility of the combination of allopurinol and febuxostat. In case of gout that does not respond to the main methods of therapy, treatment with pegloticase is recommended. When prescribing urate-lowering therapy, dose titration is necessary, to avoid the development of toxic effects.

Topics: Algorithms; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Gout; Humans; Uric Acid

Urate lowering therapy (ULT) should, according to recent guidelines, be initiated in the majority of cases already after the first attack of gout. Allopurinol is the first line choice of ULT and should be started with low dose, which is increased until the treatment target is reached. The treatment target should be a blood urate of < 360 µmol/l or < 300 µmol/l (in the presence of topfi), which should be maintained until topfi have resolved. NSAID/cox-inhibitors, colchicine and glucocorticoids are all valid short-term treatments of gout attacks. ULT should not be paused/terminated during attacks and can be initiated during an attack that is adequately treated. Recent RCTs of ULT treatment have demonstrated the importance of thorough and adequate information to the patient and regular follow-up until treatment targets are reached. Such a strategy improve both compliance and outcomes of ULT treatment.

Topics: Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid

To assess the impact of allopurinol on diabetes in a retrospective cohort of Veterans' Affairs patients with gout.The New York Harbor VA computerized patient record system was searched to identify patients with an ICD-9 code for gout meeting at least 4 modified 1977 American Rheumatology Association gout diagnostic criteria. Patients were divided into subgroups based on >30 continuous days of allopurinol, versus no allopurinol. New diagnoses of diabetes, defined according to American Diabetes Association diagnostic criteria or clinical documentation explicitly stating a new diagnosis of diabetes, were identified during an observation period from January 1, 2000 through December 31, 2015.Six hundred six gout patients used allopurinol >30 continuous days, and 478 patients never used allopurinol. Over an average 7.9 ± 4.8 years of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (11.7/1000 person-years vs 10.0/1000 person-years, P = .27). A lower diabetes incidence in the longest versus shortest quartiles of allopurinol use (6.3 per 1000 person-years vs 19.4 per 1000 person-years, P<.0001) was attributable to longer duration of medical follow-up.In this study, allopurinol use was not associated with decreased diabetes incidence. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity, and diabetes, and the potential impact of gout treatments on diabetes incidence.

Topics: Aged; Aged, 80 and over; Allopurinol; Colchicine; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Incidence; Male; Medication Adherence; Middle Aged; New York; Retrospective Studies; Time Factors; United States; United States Department of Veterans Affairs; Uric Acid

Topics: Allopurinol; Diabetes Mellitus, Type 1; Disease Progression; Gout; Humans; Kidney; Renal Insufficiency, Chronic; Uric Acid

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Prospective Studies

To evaluate a 12-week course of combined alloturinol-lowering therapy with a prophylactic anti-inflammatory dose of movalis for the frequency of exacerbations and the quality of life of patients with gout.. Allopurinol was administered orally, 1 time per day. Every 3 weeks, the dosage of the drug was increased by 50 mg to 300 mg per day under the control of the level of serum uric acid (sUA). The total daily dose of the drug movalis, used in the form of different dosage forms, was 7.515 mg. The clinical effectiveness of the treatment was evaluated after 3, 6, 9 and 12 weeks according to physical examination, the dynamics of joint pain at rest, during movement and palpation, according to the visual analogue scale (VAS) in millimeters, Likert scale, EuroQol-5D-5L questionnaire, care for oneself, habitual daily activities, the presence of anxiety and depression, assessment of satisfaction with treatment (on a scale of 1 to 5, where 1 is the complete absence of improvement or worsening, and 5 is a very good result); took into account the period of remission, as well as the time before the onset of relapse of gouty arthritis. An adverse event (AE) was recorded.. On the background of treatment with movalis 7.5 mg per day more than two-thirds of patients showed no worsening of the articular syndrome with an increase in the dose of allopurinol to 300 mg per day. By the 12th week of observation, a significant difference was found between the severity of gouty arthritis characteristics in the direction of improving mobility, self-care, normal daily activities, reducing soreness, reducing anxiety and depression (p0.05). In addition, the ESR and sUA levels were significantly different initially and at the final observation point (p0.05), which indicates a positive effect on the inflammatory process. A 3-month course of combination therapy was not accompanied by significant increases in blood pressure, changes in creatinine clearance in blood serum. There were no adverse events from the gastrointestinal tract. 90.9% of patients rated the treatment result as very good. AE in the form of a skin allergic rash was observed in one patient; it did not require interruption of treatment and completely stopped without consequences after completion of the course.. 12 a week-long combined therapy of the allopurinol-reducing drug with the anti-inflammatory dose movalis prevents the exacerbation of the articular syndrome and improves the quality of life of patients with gout.. Цель. Оценить влияние 12-недельного курса сочетанной уратснижающей терапии аллопуринолом, препаратом 1-й линии для достижения целевого уровня мочевой кислоты, на фоне профилактического противовоспалительного приема препарата Мовалис на частоту обострений и качество жизни больных подагрой. Материалы и методы. Аллопуринол назначался внутрь, 1 раз в день. Каждые 3 нед дозировка препарата увеличивалась на 50 мг до 300 мг в день под контролем уровня сывороточной мочевой кислоты. Суммарная суточная доза препарата Мовалис, применяемого в виде разных лекарственных форм, составляла 7,515 мг. Клиническую эффективность лечения оценивали через 3, 6, 9 и 12 нед по данным физикального осмотра, динамике суставной боли в покое, при движении и пальпации, по визуальной аналоговой шкале в миллиметрах, шкале Лайкерта, опроснику EuroQol-5D-5L, уходу за собой, привычной повседневной деятельности, наличию тревоги и депрессии, оценке удовлетворенности лечением (по шкале от 1 до 5, где 1 полное отсутствие улучшения или ухудшение, а 5 очень хороший результат); учитывали период ремиссии, а также время до появления рецидива подагрического артрита. Проводилась регистрация неблагоприятных явлений. Результаты и обсуждение. На фоне лечения Мовалисом 7,5 мг в день больше чем у 2/3 пациентов не отмечалось ухудшения суставного синдрома при увеличении дозы аллопуринола до 300 мг в день. К 12-й неделе наблюдения выявлено достоверное различие между выраженностью характеристик подагрического артрита в сторону улучшения показателей подвижности, ухода за собой, привычной повседневной деятельности, снижения болезненности, уменьшения тревоги и депрессии (p0,05). Кроме того, достоверно различались уровни СОЭ и сывороточной мочевой кислоты исходно и в конечной точке наблюдения (p0,05), что свидетельствует о положительном влиянии на воспалительный процесс. Трехмесячный курс комбинированной терапии не сопровождался значительными подъемами артериального давления, изменениями клиренса креатинина в сыворотке крови. Отсутствовали нежелательные явления со стороны желудочно-кишечного тракта. Результат лечения как очень хороший оценили 90,9% пациентов. Неблагоприятное явление в виде кожной аллергической сыпи отмечалось у одного больного, оно не потребовало прерывания лечения и полностью купировалось без последствий после завершения курса. Заключение. Двенадцатинедельная сочетанная терапия уратснижающим препаратом аллопуринолом на фоне противовоспалительного приема препарата Мовалис предотвращает обострение с

Topics: Allopurinol; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Hyperuricemia; Meloxicam; Pharmaceutical Preparations; Quality of Life; Uric Acid

Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction. Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.

Topics: Aged; Allopurinol; Gout; Gout Suppressants; Humans; Male; Meningitis, Aseptic; Tomography, X-Ray Computed; Unconsciousness

The safety and efficacy of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) are still unclear owing to a lack of studies in these patients. Therefore, we aimed to evaluate the effect of febuxostat on renal function, general safety, and efficacy in gout patients with stage 4-5 CKD.. Among 739 patients who had been administered febuxostat from May 2012 to December 2016 at a single hospital in Korea, 370 patients who had been monitored for 1 year were analyzed. Serum uric acid levels and estimated glomerular filtration rate (eGFR) of patients with gouty arthritis were collected at baseline and 1 year after febuxostat administration.. Among the 370 patients, 280 patients were stage 1-3 CKD, 63 patients were stage 4-5 CKD, and 27 patients were on dialysis. The eGFR of 63 patients with stage 4-5 CKD, excluding dialysis patients, was 19.84 ± 7.08 mL/min/1.73 m2 when they began to take febuxostat and 23.49 ± 16.67 mL/min/1.73 m2 after 12 months (p = 0.13). The urate-lowering effect after 12 months of febuxostat medication showed statistical significance (8.96 ± 2.31 mg/dL at baseline and 4.88 ± 1.68 mg/dL after 12 months, p < 0.01). The difference in incidence of adverse events among patients with stage 1-3 CKD, those with stage 4-5 CKD, and those on dialysis was not significant.. Febuxostat demonstrated renal safety and good urate-lowering efficacy in gout patients with stage 4-5 CKD, who are not yet on dialysis.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Dialysis; Renal Insufficiency, Chronic; Republic of Korea; Treatment Outcome; Uric Acid

To compare outcomes of 2 gout clinics that implemented different treatment strategies.. Patients newly diagnosed with gout and a follow-up of 9-15 months were included. Co-primary outcomes were the proportion of patients reaching a serum uric acid (UA) ≤0.36 mmoles/liter and free of flares. Secondary outcomes were the proportion of patients requiring treatment intensification and experiencing adverse events. One clinic adopted a strict serum UA (≤0.30 mmoles/liter target) strategy, with early addition of a uricosuric to allopurinol, and the other clinic adopted a patient-centered (PC) strategy emphasizing a shared decision based on serum UA and patient satisfaction with gout control. Independent t-tests or chi-square tests were used to test differences in outcomes, and logistic regressions were used to adjust the effect of the treatment center on outcomes for confounders.. In total, 126 and 86 patients had a follow-up mean ± SD of 11.3 ± 1.8 versus 11.1 ± 1.9 months. In the UA strategy, 105 of 126 patients (83%) compared to 63 of 86 (74%) in the PC strategy (P = 0.10) reached the threshold of ≤0.36 mmoles/liter; and 58 of 126 (46%) versus 31 of 86 (36%) were free of flares (P = 0.15). In the UA strategy, 76 of 126 patients (60%) were on allopurinol monotherapy compared to 63 of 86 (73%) in the PC strategy (P = 0.05), yet the number of adverse events was not different (n = 25 [20%] versus n = 20 [23%]; P = 0.55). Adjusting for confounders did not substantially change these associations.. A strict UA strategy resulted in a nonsignificantly higher proportion of patients reaching a serum UA ≤0.36 mmoles/liter and being free of flares. This result was accomplished with significantly more therapy intensification. The small sample size plays a role in the significance of results.

Topics: Aged; Allopurinol; Clinical Decision Rules; Clinical Protocols; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Logistic Models; Male; Middle Aged; Patient Satisfaction; Precision Medicine; Symptom Flare Up; Treatment Outcome; Uric Acid; Uricosuric Agents

Few studies have systematically and quantitatively addressed the impact of urate-lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate-lowering therapy on MSU deposits in patients with gout.. In this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual-energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate-lowering therapy for a mean period of 18 months before a follow-up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquantitative scoring, and baseline and follow-up measurements were compared.. Baseline and follow-up DECT scans were available for all 83 subjects. Six subjects discontinued treatment, and 77 subjects underwent a lifestyle intervention (n = 24) or were treated with allopurinol (n = 29), febuxostat (n = 22), or benzbromarone (n = 2) over the entire observation period. The mean serum uric acid (UA) level decreased from 7.2 to 5.8 mg/dl in the overall population. In patients who discontinued treatment, no change in MSU deposits or serum UA levels was observed. The burden of MSU deposits significantly decreased in patients undergoing lifestyle intervention (MSU volume P = 0.007; MSU score P = 0.001), and in patients treated with allopurinol (MSU volume and score P < 0.001) or febuxostat (MSU volume P < 0.001; MSU score P = 0.001). No significant decline in MSU deposits was noted in patients who discontinued treatment.. These data show that lifestyle intervention and xanthine oxidase inhibitors significantly decrease the MSU deposit burden. Hence, conventional gout therapy not only lowers serum UA levels, but also reduces pathologic MSU deposits.

Topics: Aged; Alcohol Drinking; Allopurinol; Benzbromarone; Diet Therapy; Febuxostat; Female; Foot Joints; Fructose; Gout; Gout Suppressants; Humans; Male; Meat; Middle Aged; Prospective Studies; Purines; Shellfish; Tomography, X-Ray Computed; Uric Acid; Uricosuric Agents

To determine the clustering patterns of monosodium urate (MSU) crystal deposition and bone erosions among patients with gout requiring urate-lowering therapy (ULT) using dual-energy CT (DECT).. DECT scans of bilateral hands/wrists, feet/ankles, and knees were obtained on 153 patients with gout on allopurinol ≥300 mg daily for ≥3 months. Two radiologists assessed the images at pre-specified sites (15 in the hands/wrists, 12 in the feet/ankles, 4 in the knees). Clustering patterns of MSU crystal deposition and bone erosions were evaluated.. Among 153 patients with gout (mean duration, 15 years) on allopurinol (mean duration, 5 years), MSU crystal deposition (67%) affected multiple sites in the hands/wrists, feet/ankles, and knees more often than would be expected by chance (p<0.001 for all 3 regions). In the feet/ankles, bone erosions were also observed in a clustered manner (p<0.001). Presence of MSU crystal deposition at a particular joint was most strongly associated with symmetric involvement of the same joint of the opposite extremity in the hands/wrists, feet/ankles, and knees (adjusted odds ratio (OR) 26.1, 46.9, and 9.9, respectively). Similarly, presence of erosions in the feet/ankles was highly symmetric (adjusted OR 91.4). Erosions were 8-fold more likely to be present in sites with MSU crystal deposition compared to those without.. Among patients with longstanding gout on ULT, MSU crystal deposition and bone erosions affect multiple joints within the hands/wrists, feet/ankles, and knees in a highly symmetric manner. These radiologic data support the notion of MSU crystal deposition in gout as a symmetric polyarthropathy.

Topics: Aged; Allopurinol; Female; Foot Joints; Gout; Gout Suppressants; Hand Joints; Humans; Knee Joint; Male; Middle Aged; Tomography, X-Ray Computed; Uric Acid

Gout is common crystal arthritis that is often managed sub-optimally.. To determine what proportion of patients treated for gout by the tertiary level rheumatology service at the Royal Brisbane Hospital between 2014 and 2018 reached target serum urate (SU) levels. Secondary aims included exploring the demographic characteristics of those who did and did not reach target.. The records of patients who were treated at least once either as in inpatient or outpatient by the rheumatology service at the Royal Brisbane Hospital between 1 January 2014 and 31 December 2018 were reviewed. Clinical status, treatment characteristics and outcome were recorded and analysed.. There were 129 patients who met the inclusion criteria for the study, the majority of patients were male and 39% had tophaceous gout. Fifty-four (42%) had been intentionally discharged from clinic, 50 (85%) of those patients had reached their SU target, the remaining eight (15%) were discharged with a plan for other services to continue their therapy to reach SU target. Forty patients (31%) had ongoing follow up, with 16 (40%) of these at target and 24 (60%) not at target. Thirty-five (27%) were not attending, five (4%) had died and 30 (23%) had failed to attend follow-up appointments, none of these patients was at target at their last known SU level.. Despite effective therapy the number of patients treated for gout at a large public metropolitan teaching hospital reaching SU target was low. Almost one-quarter of patients in the study discontinued contact with the clinic. The reasons for this are not clear and are likely multifactorial.

Topics: Allopurinol; Australia; Female; Gout; Gout Suppressants; Humans; Male; Rheumatology; Treatment Outcome; Uric Acid

In this study, we established both an animal model and a cellular model of hyperuricemia (HUC). Subsequently, we treated these models with allopurinol (ALLO) to study the effect of uric acid (UA) and ALLO on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells (VSMC).. Western Blot, immunohistochemistry assay, and real-time polymerase chain reaction were conducted to measure the changes in the expression of differentiation-related factors in osteoblasts and VSMCs in HUC and HUC+ALLO groups. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry were utilized to observe the changes in the proliferation of osteoblasts in HUC and HUC+ALLO groups. Von Kossa staining was performed along with calcium content measurement to investigate the effect of HUC/ALLLO on vascular calcification.. In this study, the levels of Wnt3a and differentiation-related factors, including Runx2, Sp7, Ibsp, Bglap, Dmp1, and Col1a1, were all evidently decreased in HUC rats, while the presence of ALLO increased the levels of above factors. In addition, the viability of osteoblasts was reduced while their apoptosis was elevated in the HUC group, and ALLO treatment reduced the apoptosis and increased the viability of osteoblasts to a certain extent. Moreover, HUC elevated the levels of Wnt3a, Runx2, Sp7, Bglap, Col1a1, SM22a, and Acta2 in VSMCs of HUC rats, leading to greatly increased calcium content and obvious vascular calcification. In contrary, ALLO treatment reduced the effect of HUC. Furthermore, the effect of UA and ALLO on osteoblasts and VSMCs was also validated in cellular models treated with monosodium urate (MSU) crystals or MSU+ALLO.. HUC can suppress the differentiation and proliferation of osteoblasts while promoting the differentiation of VSMCs both in vivo and in vitro. The treatment by ALLO exhibited a therapeutic effect on HUC by promoting the differentiation and proliferation of osteoblasts while reducing vascular calcification.

Topics: Allopurinol; Animals; Apoptosis; Bone Diseases, Metabolic; Cell Differentiation; Cell Proliferation; Gout; Gout Suppressants; Hyperuricemia; Male; Muscle, Smooth, Vascular; Osteoblasts; Rats; Rats, Sprague-Dawley; Vascular Calcification

In this study, treatment and the serum uric acid (UA) level were compared using medication history generated by prescription order records of antihyperuricemic to examine the treatment success rate. We examined the treatment success rate among these patients based on the serum UA level during 120-180 days after the initiation of treatment, which was set as the endpoint. The number of patients whose UA level before the start of treatment was > 8.0 mg/dL but decreased to < 6.0 mg/dL after the treatment, which is the target treatment success, was 92 (success rate of 14.2%), 50 (53.2%), 76 (41.5%), 35 (31.9%), and 45 (37.8%) in the allopurinol 100 mg/day (A1) and 200 mg/day (A2), febuxostat 10 mg/day (F1) and 20 mg/day (F2), and benzbromarone 50 mg/day (B), respectively. Compared with that of the other drugs, the treatment success rate was high with A2 and low with A1. From the generated medication history, the treatment success rate with antihyperuricemic can be extracted mechanically.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Treatment Outcome; Uric Acid

BACKGROUND Pancytopenia is a hematological condition which is characterized by decreases in all three cellular elements: RBC, WBC, and platelets. As a result, patients with pancytopenia are more prone to anemia, infections, and excessive bleeding. Pancytopenia can be caused by medications or drug interactions that suppress the bone marrow. This case report highlights a drug interaction between allopurinol and mercaptopurine which led to pancytopenia and septic infection, resulting in the patient's death. This could easily have been avoided if a clinical pharmacist had been consulted. CASE REPORT A 55-year-old female patient with a past medical history of gout, depression, back pain, and type 2 diabetes was recently diagnosed with ulcerative colitis and was discharged with a new prescription of mercaptopurine. After 2 months of concurrent use of allopurinol and mercaptopurine, she developed infected foot ulcers, which progressed rabidly to sepsis. At the time, her laboratory findings confirmed pancytopenia. Despite treatment, the patient died. CONCLUSIONS This case illustrates the importance of consulting a clinical pharmacist in order to avoid such medical error. The dose of mercaptopurine should be reduced to 25% of the recommended dose when it is given concurrently with allopurinol to reduce the risk of pancytopenia. Health care providers should think about the significant role of clinical pharmacy services. In our case, there were no clinical pharmacist involved in the care of this patient, and as a result of such negligence, the patient lost her life.

Topics: Allopurinol; Colitis, Ulcerative; Diabetic Foot; Drug Interactions; Fatal Outcome; Female; Gout; Gout Suppressants; Humans; Immunosuppressive Agents; Mercaptopurine; Middle Aged; Pancytopenia; Pharmacists; Pharmacy Service, Hospital; Referral and Consultation; Sepsis

To characterise adherence and treat-to-target (T2T) strategy in gout patients within a Swiss tertiary hospital.. Consecutive presenting patients with proven gout were prospectively included in this cohort. Symptoms, comorbidities, medication and laboratory values were assessed (during hospitalisation and at planned 3- and 12-month follow-up assessments).. 116 patients (98 men) with a mean age of 67 (range 23–94 years) were included, 74% of whom had active arthritis. Comorbidities were frequent: hypertension, renal impairment, and obesity were present in 72, 55 and 35% of patients, respectively. Thirty-five percent of patients received urate-lowering treatment at inclusion. Only 62 and 50% attended the 3- and 12-month follow-up. The target serum uric acid level of <360 μmol/l was achieved in 22 and 57% of patients by the 3- and 12-month follow-up visits, respectively. Patients followed up by rheumatologists reached the target serum uric acid at follow-up more often than those that were not (p = 0.033). Median daily allopurinol dose at 12-month follow-up was 300 mg in those achieving T2T and 100 mg in the others (p = 0.033). Flares occurred during the first 3 months in 52% and during the subsequent 9 months in 47% of patients.. Only half of patients attended the planned follow-up visits, indicating low awareness for gout. Of those attending follow-up, only approximately 50% had achieved the serum urate target at 12 months. Although new treatments are available, care for gout patients remains insufficient, notably in difficult-to-treat multimorbid patient subsets as described in this cohort.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Longitudinal Studies; Male; Middle Aged; Multimorbidity; Patient Acceptance of Health Care; Switzerland; Uric Acid; Young Adult

The aim of this project was to determine the effects of a package of care for gout in primary care.. An audit of gout management in a single rural medical practice was undertaken before (in 2012) and after (in 2015) the introduction of the package of care reflecting guidelines in gout management.. There was a statistically significant increase in the number of individuals commenced on allopurinol ≤100 mg/d and a decrease in the number commenced on allopurinol ≥200 mg/d (P <0.001). The number of times each patient had serum urate tested between 2012 and 2015 (median [range] 1 [0-3] versus 2 [0-10], respectively; P <0.001). Of those individuals who had at least one serum urate measurement, the number of individuals who were never at target urate was 43 out of 67 (64.2%) in 2012, compared with 52 out of 133 (39.1%) in 2015 (P = 0.001).. A package of care can improve adherence to gout management guidelines in primary care.

Topics: Aged; Allopurinol; Clinical Audit; Clinical Chemistry Tests; Clinical Protocols; Colchicine; Comorbidity; Diabetes Mellitus; Disease Management; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Hyperlipidemias; Hypertension; Hyperuricemia; Male; Mass Screening; Middle Aged; New Zealand; Obesity; Patient Education as Topic; Practice Guidelines as Topic; Primary Health Care; Referral and Consultation; Renal Insufficiency, Chronic; Rheumatology; Rural Population; Uric Acid

This study investigates the association between exposure to urate-lowering drugs (ULDs) and progression and recovery from chronic kidney disease (CKD).. We identified 5860 incident gout patients at Chang Gung Memorial Hospital from 2012 to 2015. Propensity score (PS)-weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) for CKD progression and improvement. A separate analysis was conducted to assess the HR for CKD progression and CKD recovery among those with worsening CKD.. The incidence of CKD progression among allopurinol, febuxostat and uricosuric agent users were 1.98, 1.88 and 1.64 per 1000 person-days. Compared with allopurinol users, the PS-weighted HR (95% confidence intervals [CIs]) was 1.77 (0.85-1.76) for febuxostat users and 1.37 (0.71-1.37) for uricosuric agent users for CKD progression and 1.43 (1.26-1.62) for febuxostat users and 1.00 (0.88-1.14) for uricosuric agent users for CKD improvement. Compared to allopurinol users, the HRs for CKD progression were 1.14 (0.80-1.66) for febuxostat users and 0.92 (0.67-1.31) for uricosuric agent users. Among 741 patients who had CKD progression, the incidence of CKD recovery was 1.33, 6.21 and 3.53 per 1000 person-days for allopurinol, febuxostat and uricosuric agent users. The HRs (95% CIs) for recovery in febuxostat and uricosuric agent users were 2.17 (1.40-3.47) and 1.80 (1.20-2.83) compared to allopurinol users.. CKD progression and recovery are common in gout patients using ULDs. Febuxostat and benzbromarone were associated with a similar risk of CKD progression with allopurinol, which has a poorer recovery compared with other ULDs.

Topics: Allopurinol; Benzbromarone; Disease Progression; Febuxostat; Female; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Recovery of Function; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid; Uricosuric Agents

Allopurinol is commonly prescribed for gout, and its clinical use may expand with ongoing trials assessing its potential cardiorenal benefits. Because heart disease has been suggested to be a risk factor for allopurinol-associated severe cutaneous adverse reactions, we sought to confirm this association in a Canadian general population cohort.. We used population data from British Columbia, Canada, to identify all incident allopurinol users between 1997 and 2015. We examined the association between heart disease (ischemic heart disease and heart failure) and the risk of hospital admission for severe cutaneous adverse reactions, adjusting for known and purported risk factors. We also evaluated the joint effects of combined clinical and demographic risk factors.. Among 130 325 allopurinol initiators, 109 hospital admissions occurred for allopurinol-associated severe cutaneous adverse reactions. The multivariable relative risk among those with heart disease was 1.55 (95% confidence interval 1.01-2.37). Patients with heart disease and chronic kidney disease who were started on an allopurinol dosage of greater than 100 mg/d had an 11-fold higher risk. Allopurinol initiation at a lower dosage among patients with heart disease and chronic kidney disease resulted in a fivefold reduction in risk. Older women with heart disease from regions with large Asian populations had a 23-fold higher risk of allopurinol-associated severe cutaneous adverse reactions than younger men without heart disease from other regions.. Heart disease is independently associated with risk of allopurinol-associated severe cutaneous adverse reactions, similar to chronic kidney disease, and low-dosage allopurinol initiation may substantially mitigate this risk. Risk factors for these rare but serious reactions should be considered when initiating allopurinol.

Topics: Age Factors; Aged; Allopurinol; Asian People; British Columbia; Dose-Response Relationship, Drug; Drug Eruptions; Ethnicity; Female; Gout; Gout Suppressants; Heart Failure; Hospitalization; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Sex Factors

This study aimed to determine colorectal cancer (CRC) risks among patients with gout through a follow-up study on a nationwide population-based cohort that included patients with gout and the general population in Taiwan.. From the Taiwan National Health Insurance Research Database, we identified 28 061 patients who were newly diagnosed with gout between 2000 and 2010 as the study cohort. We randomly selected 84 248 subjects matching in gender, age and baseline year as comparison cohort. The cohorts were followed up until CRC occurrence, withdrawal from the system of National Health Insurance, or Dec. 31, 2013.. Cumulative incidences and incidence rate ratios (IRRs) of CRC between two cohorts were examined. The Cox proportional hazards model was used to evaluate risk factors associated with CRC development.. During the 13-year follow-up, the incidence rate of CRC development in the gout cohort reached 2.44 per 1000 person-years, which was higher than the 2.13 per 1000 person-years in the control cohort (IRR=1.15; 95% CI 1.04 to 1.26). After adjusting for age, gender, urbanisation status and comorbidities, including hypertension, diabetes and hyperlipidaemia, gout showed no significant association with increased risk of CRC occurrence (adjusted HR=1.03; 95% CI 0.93 to 1.14).. Similar risks of CRC incidence were observed in patients with and without gout in Taiwan. Allopurinol and colchicine are commonly used as urate-lowering drug and anti-inflammation medication in Taiwan and had been shown to reduce the risk of CRC incidence. Thus, further pharmaco-epidemiological studies should be carried out to specifically assess the role of allopurinol in the relationship between gout and CRC.

Topics: Adult; Aged; Allopurinol; Colchicine; Colorectal Neoplasms; Comorbidity; Databases, Factual; Diabetes Mellitus; Female; Follow-Up Studies; Gout; Humans; Hyperlipidemias; Hypertension; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk Factors; Taiwan

For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat.. We carried out a case/non-case study of the World Health Organization's VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results' stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs).. Among 3509 "suspected drug" notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05-6.36] and 3.25 [3.05-3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74-13.82] vs. 3.14 [2.69-3.67] for febuxostat and 4.45 [4.04-4.91] vs. 2.29 [2.11-2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs.. Acute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Pharmacovigilance; Product Surveillance, Postmarketing; Treatment Outcome

The connection between gout and various cancers remains unclear. We assessed the relationship between gout and colorectal cancer in a population of veterans.. We reviewed the Computerized Patient Record System of the VA New York Harbor Health Care System to assess the 10-year occurrence of colorectal cancer in patients with gout undergoing colonoscopy, versus patients with osteoarthritis but no gout.. Gout and osteoarthritis subjects were similar in age, ethnicity, body mass index, and smoking history. Among 581 gout and 598 osteoarthritis subjects with documented colonoscopies, the 10-year prevalence of colorectal cancer was significantly lower in gout (0.8%) versus osteoarthritis (3.7%) (p = 0.0008) patients. Differences in colorectal cancer rates remained significant after stratifying for nonsteroidal anti-inflammatory drug use. Among gout subjects, use of colchicine and/or allopurinol, as well as the presence/absence of concomitant osteoarthritis, did not influence colorectal cancer occurrence. On subanalysis, differences in colorectal cancer occurrence between gout and osteoarthritis subjects persisted among those who underwent diagnostic (0.5% in gout vs 4.6% in osteoarthritis subjects, p < 0.001) but not screening (0.9% in gout subjects vs 1% in osteoarthritis subjects, p = 1.0) colonoscopy. There was no significant difference in nonmalignant colorectal polyp occurrence between gout and osteoarthritis subjects.. Subjects with gout had decreased colonoscopy-documented occurrence of colorectal cancer compared with osteoarthritis subjects, suggesting a possible protective effect.

Topics: Allopurinol; Colchicine; Colonoscopy; Colorectal Neoplasms; Comorbidity; Correlation of Data; Early Detection of Cancer; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Osteoarthritis; Prevalence; United States; Veterans Health; Veterans Health Services

Topics: Adult; Allopurinol; Biopsy, Needle; Debridement; Foot Ulcer; Gout; Humans; Immunohistochemistry; India; Male; Pain Measurement; Risk Assessment; Severity of Illness Index; Treatment Outcome; Uric Acid; Wound Healing

Topics: Aged; Allopurinol; Combined Modality Therapy; Cryotherapy; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Image-Guided Biopsy; Iontophoresis; Knee Joint; Magnetic Resonance Imaging; Male; Physical Therapy Modalities; Tendons

Nowadays, there is increased interest in the connection of gout and asymptomatic hyperuricemia with comorbid conditions such as diabetes mellitus, cardiovascular diseases, hypertension, chronic kidney disease and other. Studies conducted over the past few decades suggest that not only gout, but also asymptomatic hyperuricemia can significantly worsen the prognosis in patients with cardiovascular diseases, as the deposition of urate crystals can be both an immediate cause and a factor in the progression of renal failure. In that way, the timely appointment of urate - lowering therapy and achieving the target serum uric acid level can not only affect joint damage, but also can significantly slow the progression of life - threatening comorbid conditions.. В настоящее время возрос интерес к связи подагры и асимптоматической гиперурикемии с коморбидными заболеваниями и состояниями, такими как сахарный диабет типа 2, артериальная гипертензия и другие сердечно - сосудистые патологии, хроническая болезнь почек и т.д. Проведенные за последние несколько десятилетий исследования свидетельствуют о том, что не только подагра, но и бессимптомное повышение сывороточного уровня мочевой кислоты может значительно ухудшать прогноз у пациентов с сердечно - сосудистыми заболеваниями, также отложение кристаллов моноурата натрия может быть как непосредственной причиной, так и фактором прогрессирования почечной недостаточности. Таким образом, своевременное назначение уратснижающей терапии и достижение целевого уровня мочевой кислоты способно не только повлиять на поражение суставов, но и может существенно замедлить прогрессирование жизнеугрожающих коморбидных состояний.

Topics: Allopurinol; Comorbidity; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Prevalence; Uric Acid

To assess whether gout is associated with a higher or lower risk of a new diagnosis of giant cell arteritis (GCA) in older adults, adjusting for known risk factors of GCA.. We used the 5% Medicare claims to conduct a multivariable Cox regression analyses to assess the association of gout with incident GCA in adults 65 years or older adjusting for age, gender, race (known risk factors for GCA) and Charlson-Romano comorbidity score, the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.. There were 3004 incident cases (new diagnosis) of GCA with crude incidence rates of GCA of 28.0/100,000 person-years in patients without gout and 63.8/100,000 person-years in patients with gout. Multivariable-adjusted analyses showed that preexisting gout was associated with a higher risk of incident/new GCA diagnosis with a hazard ratio of 2.05 (95% CI: 1.76, 2.40), confirmed in sensitivity analyses that substituted continuous Charlson-Romano comorbidity score with categorized score or individual comorbidities (plus hypertension, hyperlipidemia, and coronary artery disease). Older age, female gender, white race and higher comorbidity index, were also associated with a higher hazard of GCA. Subgroup analyses did not show any significant variation of the association of preexisting gout with incident GCA by age, race or sex.. Gout was associated with more than 2-fold higher risk of incident GCA in older adults, independent of known risk factors of GCA. Future studies should explore the underlying mechanisms for this association.

Topics: Age Distribution; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Female; Geriatric Assessment; Giant Cell Arteritis; Gout; Humans; Incidence; Insurance Claim Review; Male; Medicare; Multivariate Analysis; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Sex Distribution; United States

Lesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.. Safety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).. In the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.. At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Humans; Kidney Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Thioglycolates; Treatment Outcome; Triazoles; Uric Acid; Xanthine Oxidase; Young Adult

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Rheumatology; United States Food and Drug Administration

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Rheumatology; United States Food and Drug Administration

Topics: Allopurinol; Febuxostat; Gout; Humans; Rheumatology; United States; United States Food and Drug Administration

Topics: Allopurinol; Drug Prescriptions; Gout; Gout Suppressants; Humans; Renal Insufficiency, Chronic

The management of gout in chronic kidney disease and end-stage renal disease is challenging and remains controversial. There are limited data on the use of urate-lowering therapy in people receiving dialysis.. To estimate the point prevalence of gout, gout treatment and achievement of target serum urate (SU) among adults treated with long-term dialysis.. Three secular cohorts of adults receiving dialysis for at least 90 days on 1 February 2017, 1 January 2016 and 1 January 2015 were identified. Medical records were reviewed for SU concentrations. Results were compared between haemodialysis (HD) and peritoneal dialysis (PD), and participants prescribed and not prescribed urate-lowering therapy. The percentage reduction in SU 24- and 48-h post-HD was estimated based on data from a previous study. SU concentrations were then used to estimate the percentage time the SU was <0.36 mmol/L using linear interpolation.. Of 216 dialysis patients, 61 (point prevalence 28.2%, 95% confidence interval 22.35-34.8%) had a diagnosis of gout. The mean (SD) age among those with gout was 61 years (14.4), 46 (75.4%) were men and 18 (31.1%) identified as Māori or Pacific Island. Forty-two (68.9%) were prescribed allopurinol (mean (SD) dose 116.0 ± 66.9 mg/day). 46% had a predialysis SU ≤0.36 mmol/L on less than 25% of occasions and 23% were below target on 76-100% of occasions. SU was below target 41% of time, with no statistically significant difference in those on HD or PD (P = 0.39), and those prescribed or not prescribed allopurinol (P = 0.55).. Gout is experienced by approximately one in four adults treated with dialysis and two-thirds are prescribed allopurinol. A minority have SU at a target sufficient to prevent gout despite allopurinol and HD. A treat to target SU should be considered in those with SU above target.

Topics: Aged; Allopurinol; Cohort Studies; Cross-Sectional Studies; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome; Uric Acid

Febuxostat has superior renal safety to allopurinol, but data on its hepatic safety are limited. Thus we compared the hepatotoxicity of febuxostat and allopurinol, and the clinical factors associated with hepatotoxicity, in patients with gout and fatty liver disease (FLD).. We included gout patients treated with allopurinol or febuxostat who were diagnosed with fatty liver based on ultrasonography or computed tomography. Hepatotoxicity was defined as follows: (1) elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) at least 3× the upper limit of normal, when the baseline AST/ALT was normal; or (2) doubling of the baseline AST/ALT, when the baseline AST/ALT was elevated. The factors associated with hepatotoxicity were evaluated by Cox regression analysis.. Of 134 patients identified with gout and FLD, 32 (23.9%) received febuxostat and 102 (76.1%) received allopurinol. There were no significant differences in age, body mass index, comorbidity, or disease severity between the groups; however, the incidence of hepatotoxicity was significantly lower in the febuxostat group (3/32, 9.4%) than in the allopurinol group (36/102, 35.3%, p = 0.005). Diabetes (HR 3.549, 95% CI 1.374-9.165, p = 0.009) and colchicine use (HR 11.518, 95% CI 5.515-24.054, p < 0.001) were associated with a higher risk of hepatotoxicity, whereas febuxostat use was associated with a lower risk of hepatotoxicity (HR 0.282, 95% CI 0.086-0.926, p = 0.037).. In the 32 patients studied, febuxostat was well tolerated in patients with gout and FLD. However, the presence of diabetes and colchicine use may increase the risk of hepatotoxicity.

Topics: Adult; Allopurinol; Analysis of Variance; Cohort Studies; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatty Liver; Febuxostat; Female; Gout; Gout Suppressants; Humans; Liver; Liver Function Tests; Male; Middle Aged; Multivariate Analysis; Prognosis; Retrospective Studies; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler

In the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial conducted by White et al. (March 29 issue from NEJM), all-cause mortality and cardiovascular mortality are found to be higher among patients randomly assigned to febuxostat compared to allopurinol, but significant flaws are a clear lack of treat to target strategy with more powered treatment in the febuxostat arm, dysbalance with cardiovascular risk factors selectively in again the febuxostat arm, and discontinuation of the trial regimen in over 50% of patients with discontinuation of follow-up in about 45%. With these flaws, conclusions such as febuxostat-associated higher mortality are potentially if not probably incorrect, and thus febuxostat to be used not as first-line therapy may well be an invalid consequence? The paper here describes potential lessons to be taken.

Topics: Allopurinol; Cardiovascular Diseases; Cause of Death; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors

Medication non-adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout; however, non-adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008-2010, an adherence-enhancing program was implemented at the rheumatology division of a public tertiary hospital. The cost-effectiveness of this program has not been fully evaluated. With healthcare resources being finite, the value of investing in adherence-enhancing interventions should be ascertained. This study aims to evaluate the cost-effectiveness of this adherence-enhancing program to inform optimal resource allocation toward better gout management.. Adopting a real-world data approach, we utilized patient clinical and financial records generated in their course of routine care. Intervention and control groups were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and effect data were followed through 1-2 years. A decision tree was developed in TreeAge using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty.. At an assumed willingness-to-pay threshold of $50 000 USD ($70 000 SGD) per quality-adjusted life year (QALY), the intervention had an 85% probability of being cost-effective compared to routine care. The incremental cost-effectiveness ratio was $12 866 USD per QALY for the base case and ranged from $4 139 to $21 593 USD per QALY in sensitivity analyses.. The intervention is cost-effective in the short-term, although its long-term cost-effectiveness remains to be evaluated.

Topics: Adult; Aged; Allopurinol; Cost of Illness; Cost-Benefit Analysis; Decision Trees; Drug Costs; Female; Gout; Gout Suppressants; Health Care Costs; Health Knowledge, Attitudes, Practice; Humans; Male; Medication Adherence; Middle Aged; Models, Economic; Patient Education as Topic; Program Evaluation; Quality-Adjusted Life Years; Retrospective Studies; Singapore; Time Factors; Treatment Outcome

Gout is independently associated with increased risk of type 2 diabetes mellitus (T2DM). Urate-lowering therapy (ULT) might be beneficial in lowering the risks of T2DM. Therefore, we conducted a nested case-control study to evaluate the associations between ULT and T2DM.. This study retrieved the data of 29,765 gout patients from the period of 1998-2010 by using data from Taiwan's National Health Insurance Research Database. Controls (n = 59,530) were matched at a 1:2 ratio by age, sex, and region. Multivariate Cox proportional hazards regression were performed to examine the dose-dependent relationship between ULT and T2DM.. The adjusted Hazard ratio (HR) for the association of T2DM with allopurinol or benzbromarone exposure was 1.17 (95% confidence interval (CI) 1.07-1.28) and1.09 (95% CI 1.03-1.15), respectively. The HR for the cumulative allopurinol dose was 0.87 (95% CI 0.71-1.07) for patients with dose ≤1.3 mg/day and was 1.31 (95% CI 1.13-1.52) for those with a dose >15.2 mg/day. Similarly, the HR for the cumulative benzbromarone dose was 0.85(95% CI 0.75-0.96) for patients with a dose ≤1.3 mg/day and 1.42 (95% CI 1.30-1.55) for patients with a dose>9.4 mg/day, respectively. Moreover, the average exposure dose of >100 mg/day for allopurinol and >100 mg/day for benzbromarone was associated with a 1.28-fold (95% CI 1.11-1.48) and 1.47-fold (95% CI 1.23-1.76) T2DM risk respectively. The HR for patients in aged >50 years group with cumulative dose ≤1.3 mg/day of allopurinol or benzbromarone had lower risk of T2DM (HR = 0.74, 95% CI 0.58-0.94 for allopurinol; HR = 0.79, 95% CI 0.69-0.90 for benzbromarone).. Gout patients with prolonged ULT and a high dose of ULT were associated with a significant increase in T2DM risk. Although gout patients with age greater than 50 years and a lower dose of ULT may be beneficial in lowering T2DM risk, further clinical studies need to be confirmed these associations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Case-Control Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prevalence; Proportional Hazards Models; Taiwan; Treatment Outcome; Uric Acid; Young Adult

To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate-lowering therapy (ULT) among gout patients, using 2007-2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]).. Using data from 5,467 participants in the NHANES 2015-2016, we estimated the most recent prevalence rates of gout and hyperuricemia. When the NHANES was conducted, all participants were asked about their history of gout (as diagnosed by a health professional) and medication use. Hyperuricemia was defined as having a serum urate level of >7.0 mg/dl in men and >5.7 mg/dl in women. We examined decadal trends in these estimates using data from the NHANES 2007-2016 and investigated ULT usage trends using the NHANES 2007-14 (the most recent data available to date).. In 2015-2016, the prevalence of gout was 3.9% among adults in the US (9.2 million people), with 5.2% [5.9 million] in men and 2.7% [3.3 million] in women. Mean serum urate levels were 6.0 mg/dl in men and 4.8 mg/dl in women, and hyperuricemia prevalence rates were 20.2% and 20.0%, respectively. The prevalence rates of gout and hyperuricemia remained stable between 2007 and 2016 (P for trend > 0.05). The prevalence of ULT use among patients with gout was 33% in 2007-2014 and remained stable over time (P for trend > 0.05).. In this nationally representative survey sample of adults in the US, the prevalence rates of gout and hyperuricemia remained substantial, albeit unchanged, between 2007 and 2016. Despite these rates, only one-third of gout patients were receiving ULT.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Nutrition Surveys; Prevalence; Probenecid; United States; Uric Acid; Uricosuric Agents; Young Adult

Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Rheumatology; Risk Factors; United States Food and Drug Administration

Allopurinol carries a well-known risk of cutaneous adverse reactions (CARs). Although febuxostat, a xanthine-oxidase inhibitor with different chemical structure, has been considered an alternative to allopurinol, post-marketing case reports of life-threatening febuxostat-related CARs have been reported. We aimed to compare the risk of CARs between allopurinol and febuxostat in real-world settings and to assess the impact of the market entry of febuxostat on allopurinol use and associated CARs.. A nationwide study was conducted using Taiwan's National Health Insurance Research Database. In the new-user cohort study, patients who received their first prescriptions of allopurinol or febuxostat were included, and Poisson regression was used to estimate the incidence rate ratios (IRRs) of CARs. In the interrupted time series analysis, time series data on new users and incidence rate of CARs were divided into three periods based on the reimbursement scheme of febuxostat in Taiwan, and segmented regression models were used to estimate changes in both the level and trend in each period.. We identified 526 cases of CARs with 487 among new users of allopurinol and 39 among new users of febuxostat (incidence rate: 15.37 vs 3.48 per 1000 person-years). Allopurinol was associated with higher risk of CARs (adjusted IRR 5.55, 95% CI [3.97-7.76]), mild CARs (1.86, [1.24-2.81]), severe CARs (16.75, [8.87-31.62]) and fatal CARs (16.18, [5.05-51.83]) than febuxostat. The overall incidence rates of xanthine-oxidase inhibitor-related CARs decreased from 15.28 to 14.28 per 1000 person-years after the initial reimbursement of febuxostat and further decreased to 9.46 after the reimbursement coverage of febuxostat expanded; however, the changes were not statistically significant.. Febuxostat can be considered an alternative for patients carrying risk factors for allopurinol-related CARs. However, since there were fatal cases of febuxostat-related CARs, the closely monitoring of symptoms of CARs during the initiation of febuxostat is still warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Child; Child, Preschool; Cohort Studies; Drug Eruptions; Febuxostat; Female; Gout; Gout Suppressants; Humans; Infant; Infant, Newborn; Interrupted Time Series Analysis; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Young Adult

Allopurinol reduces oxidative stress and may thus have an anti-inflammatory effect. Previous studies suggest that allopurinol use might decrease the risk of prostate cancer (PCa) among gout patients. We studied the association between allopurinol use and PCa incidence.. The cohort consists of 76,874 men without prevalent PCa, originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). The follow-up started at entry to the trial. We excluded men using allopurinol in the year before entry (wash-out). PCa cases detected during 1996-2015 were identified from the Finnish Cancer Registry. Information on tumor Gleason score and TNM stage were obtained from medical files. Information on PSA level was obtained from screening samples for men in the FinRSPC screening arm and from laboratory databases for men in the control arm. Information on BMI was based on a questionnaire sent to men in the FinRSPC screening arm in 2004-2008. Drug purchase information were obtained from the national prescription database. We used Cox regression (adjusted for age, FinRSPC trial arm, PCa family history and use of other medication) to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of PCa risk by allopurinol use. We analyzed medication as a time-dependent variable to minimize immortal time bias.. There were 9062 new PCa diagnoses in the cohort. Follow-up time did not differ by allopurinol use (median 17 yr; IQR 11-19 vs median 17 yr; IQR 12.33-19). The risk of PCa did not differ by allopurinol use (multivariable adjusted HR 1.03; 95% CI 0.92-1.16). Allopurinol use did not associate with the risk of high-grade or metastatic cancer. Cumulative duration or average yearly dose of allopurinol use showed no association with PCa risk. No delayed risk associations were observed in the lag-time analyses.. We observed no difference in the PCa risk by allopurinol use.

Topics: Aged; Allopurinol; Databases, Factual; Drug Prescriptions; Finland; Follow-Up Studies; Gout; Gout Suppressants; Humans; Incidence; Male; Mass Screening; Middle Aged; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; Time Factors

Topics: Allopurinol; Gout; Humans; Oxypurinol

Topics: Aged; Allopurinol; Cardiovascular Diseases; Cohort Studies; Febuxostat; Gout; Gout Suppressants; Humans; Patients; Population; Risk Factors

Topics: Allopurinol; Biopsy; Brain; Drug Hypersensitivity Syndrome; Gout; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Skin; Young Adult

Topics: Aged; Allopurinol; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Uric Acid; Xanthine Oxidase

ABCG2 is a high-capacity urate transporter that plays a crucial role in renal urate overload and extra-renal urate underexcretion. Previous studies have suggested an association between hyperuricemia and gout susceptibility relative to dysfunctional ABCG2 variants, with rs2231142 (Q141K) being the most common. In this study, we analyzed the ABCG2 gene in a hyperuricemia and gout cohort focusing on patients with pediatric-onset, i.e., before 18 years of age.. The cohort was recruited from the Czech Republic (n = 234) and consisted of 58 primary hyperuricemia and 176 gout patients, with a focus on pediatric-onset patients (n = 31, 17 hyperuricemia/14 gouts); 115 normouricemic controls were used for comparison. We amplified, sequenced, and analyzed 15 ABCG2 exons. The chi-square goodness-of-fit test was used to compare minor allele frequencies (MAF), and the log-rank test was used to compare empirical distribution functions.. In the pediatric-onset cohort, two common (p.V12M, p.Q141K) and three very rare (p.K360del, p.T421A, p.T434M) allelic ABCG2 variants were detected. The MAF of p.Q141K was 38.7% compared to adult-onset MAF 21.2% (OR = 2.4, P = 0.005), to the normouricemic controls cohort MAF 8.5% (OR = 6.8, P <  0.0001), and to the European population MAF 9.4% (OR = 5.7, P <  0.0001). The MAF was greatly elevated not only among pediatric-onset gout patients (42.9%) but also among patients with hyperuricemia (35.3%). Most (74%) of the pediatric-onset patients had affected family members (61% were first-degree relatives).. Our results show that genetic factors affecting ABCG2 function should be routinely considered in a hyperuricemia/gout diagnosis, especially in pediatric-onset patients. Genotyping of ABCG2 is essential for risk estimation of gout/hyperuricemia in patients with very early-onset and/or a family history.

Topics: Adolescent; Adult; Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Child; Child, Preschool; Cohort Studies; Czech Republic; Febuxostat; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Polymorphism, Single Nucleotide; Young Adult

Gout is associated with a higher risk of atrial fibrillation (AF). Comparative effectiveness of allopurinol or febuxostat for reducing the AF risk is unknown, which was our study's main objective.. We used the 5% Medicare Beneficiary cohort (≥65 years) from 2006 to 2012 to identify people with a new filled prescription for allopurinol or febuxostat, with a baseline period of 365 days without respective medication and without AF. We used 5:1 propensity-matched Cox regression analyses to assess whether allopurinol use differed from febuxostat use regarding the hazard ratio (HR) of incident AF. We found 25 732 eligible episodes in 23 135 beneficiaries. Of these, 2311 incident allopurinol or febuxostat use episodes (9%) ended in incident AF with crude incidence rates of 8.0 and 10.5 per 100 person-years, respectively. In propensity-matched analyses, compared with allopurinol, febuxostat was associated with higher HR of AF, 1.25 [95% confidence interval (CI) 1.05-1.48]. Compared with allopurinol <200 mg/day, febuxostat 80 mg/day was associated with significantly higher HR of AF, 1.62 (95% CI 1.16-2.27), but not febuxostat 40 mg/day or higher allopurinol doses. Compared with 1-180 days of allopurinol use, febuxostat use for 1-180 days was associated with significantly higher HR of AF, 1.36 (95% CI 1.10-1.67), but longer durations were not.. Febuxostat was associated with a higher risk of AF compared with allopurinol in older adults. Increased AF risk was noted with febuxostat 80 mg/day dose and was most evident in the first 6 months of use. These findings need replication.

Topics: Aged; Allopurinol; Atrial Fibrillation; Cohort Studies; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Medicare; United States

To update the evidence about the role of elevated levels of uric acid as a risk factor for cardiovascular disease. The review includes the most recent epidemiological evidence as well as the possible mechanisms supporting the interaction between uric acid and cardiovascular, metabolic and renal disease.. The confirmed role of uric acid as involved in the onset and progression of cardiovascular and metabolic diseases. In particular, the review will focus on the possible mechanism of action of uric acid and the level of involvement of xanthine-oxidase as a mechanism responsible for both hyperuricaemia and oxidative stress. The review also briefly summarizes the most recent findings of the studies carried out with xanthine-oxidase inhibitors in patients at risk of cardiovascular disease by focusing on the possible benefits.. Elevated levels of serum uric acid have been demonstrated to be closely related to the development of cardiovascular, metabolic and renal disease. The mechanism responsible for such interaction directly or indirectly involves xanthine-oxidase activation and the inflammatory system leading to structural and functional abnormalities. Preliminary results from different trials have demonstrated the favourable effects of urate-lowering treatment in the prevention of cardiovascular disease beyond the treatment of gout.

Topics: Cardiovascular Diseases; Gout; Humans; Hyperuricemia; Risk Factors; Uric Acid; Xanthine Oxidase

To assess if gout is associated with a higher risk of incident chronic pain. This study used the 2006-2012 Medicare claims data. We used multivariable-adjusted Cox regression analyses to examine the association of pre-existing diagnosis of gout with incident (new) diagnosis of chronic pain, adjusting for demographics, medical comorbidity, and use of common medications for cardiovascular disease and gout. Sensitivity analyses substituted Charlson-Romano score with a categorical variable or each Charlson-Romano comorbidity. There were 1,321,521 eligible people, of whom 424,518 developed incident chronic pain. Crude incidence rates of chronic pain were as follows: gout, 158.1 per 1000 person-years and no gout, 64.5 per 1000 person-years. In multivariable-adjusted Cox regression analyses, gout was associated with higher hazard ratio of chronic pain, 2.02 (95% CI, 1.98, 2.05), confirmed in sensitivity analyses 1.96 (95% CI, 1.93, 1.99) (model 2) and 1.77 (95% CI, 1.74, 1.80) (model 3). No meaningful differences were found by gender and race in subgroup analyses; slightly lower hazard of chronic pain with gout was seen in oldest people. Use of allopurinol or febuxostat was associated with lower risk of chronic pain, 0.79 (95% CI, 0.77, 0.82; model 1) and 0.72 (95% CI, 0.56, 0.92; model 1). Gout was associated with a doubling of the risk of chronic pain and gout treatments with reduction in the risk. Efforts must be made to optimize gout control, so that chronic pain can be avoided as a long-term sequalae of gout and when present, treated early and appropriately. Key points • Gout was associated with twofold higher risk of incident (or new) diagnosis of chronic pain. • Gout treatments were associated with a lower chronic pain risk. • Increased risk of chronic pain with gout was similar across age, race, and sex. • Studies should examine if optimal gout control with treat-to-target approach can reduce the risk of chronic pain in people with gout.

Topics: Aged; Aged, 80 and over; Allopurinol; Chronic Pain; Comorbidity; Febuxostat; Female; Gout; Humans; Incidence; Male; Medicare; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Risk Factors; United States

Topics: Allopurinol; Drug Prescriptions; Gout; Gout Suppressants; Humans; Renal Insufficiency, Chronic

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality-adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues. Compounds with reduced clearance or increased potency were more forgiving to missed doses, however, even following relatively large changes in these properties the predicted maximum reimbursement prices represented an increase of only 19% above febuxostat 80 mg. Linked pharmacometric and pharmacoeconomic modeling methods have the potential to inform early drug development by providing an indication of pricing options that may permit reimbursement.

Topics: Allopurinol; Computer Simulation; Cost-Benefit Analysis; Costs and Cost Analysis; Drug Monitoring; Economics, Pharmaceutical; Febuxostat; Gout; Gout Suppressants; Humans; Insurance, Health, Reimbursement; Medication Adherence; Quality-Adjusted Life Years; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Rheumatology; United States Food and Drug Administration; Xanthine Oxidase

To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat.. Using 2002-2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths.. We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person-years for the primary outcome was 1.89 for allopurinol and 1.84 for febuxostat initiators. The corresponding hazard ratio comparing allopurinol vs febuxostat initiators was 1.09 (95% CI: 0.90, 1.32). No significant difference was found for the secondary outcomes, including all-cause mortality (hazard ratio 0.96; 95% CI: 0.79, 1.16). Subgroup analyses limited to those at high CV risk and to equipotent-dose initiators (i.e. allopurinol ⩾300 mg/day vs febuxostat ⩾40 mg/day) showed similar results.. Overall, this large Korean population-based study suggests no difference in the risk of non-fatal CV events and all-cause mortality between allopurinol and febuxostat initiators. These findings are consistent with the recent US Medicare population study, although the current study population consisted of younger Asians.

Topics: Aged; Allopurinol; Cardiovascular Diseases; Cohort Studies; Febuxostat; Female; Gout; Gout Suppressants; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Proportional Hazards Models; Republic of Korea; Stroke

Topics: Allopurinol; Cohort Studies; Diabetes Mellitus; Gout; Humans; Retrospective Studies

Gout patients with chronic kidney disease (CKD) accumulate the active allopurinol metabolite oxypurinol, suggesting that allopurinol may promote greater serum urate (sU) lowering in CKD patients.. We identified all patientswith gout diagnoses on either 100 mg or 300 mg of allopurinol daily, with available pre- and on-treatment sU levels, in our system in a 1-year period. Mean sU decrement by dosing per CKD groups was determined by CKD stage.. Of 1,288 subjects with gout, 180 met entry criteria, with 83 subjects receiving 100 mg and 97 receiving 300 mg allopurinol. Subjects with CKD stage 1 experienced less sU lowering with 100 mg than 300 mg of allopurinol. Subjects with stage 4 and 5 CKD had equivalent sU decreases across the 100 mg and 300 mg allopurinol groups. However, the 100 mg group started at a higher pre-treatment sU and ended at a higher final sU than the 300 mg group.. The strategy of titrating allopurinol to sU in patients with kidney impairment may result in greater sU lowering at lower doses than in patients without CKD but may also pose a treatment challenge from a possible drug ceiling effect.

Topics: Allopurinol; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gout; Gout Suppressants; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; New York; Outcome and Process Assessment, Health Care; Patient Acuity; Renal Elimination; Renal Insufficiency, Chronic; Retrospective Studies; Uric Acid; Veterans Health Services

There is a paucity of community-based data regarding the prevalence and impact of gout flares as these may often be self-managed. The aim of this study was to determine the prevalence of self-reported gout and gout flares, the use of urate-lowering therapy (ULT), and the association of gout flares with health-related quality of life (HRQoL) in a large community sample. Covariate associations with flare frequency and allopurinol use were also examined.. The South Australian Health Omnibus Survey is an annual, face-to-face population-based survey. Data collected in the 2017 survey included self-reported medically diagnosed gout, allopurinol use (first-line ULT in Australia), and gout attacks (flares) in the last 12 months, in addition to sociodemographic variables and health-related quality of life (HRQoL, SF-12). Data were weighted to the Australian Bureau of Statistics 2016 census data to reflect the South Australian population. Participants 25 years and over (n = 2778) were included in the analysis.. The prevalence of gout was 6.5% (95%CI 5.5, 7.5). Amongst participants with gout, 37.1% (95%CI 29.6, 45.3) reported currently using allopurinol, while 23.2% (95%CI 16.9, 21.0) reported prior use (38% discontinuation rate). Frequent flares (≥ 2 in the last year) were reported by 25% of participants with gout and were more likely with younger age, higher body mass index, and current allopurinol use (p < 0.05). The frequency of gout flares was associated with a lower physical HRQoL (p = 0.012). Current allopurinol use was reported by 51% of participants with frequent gout flares.. Flares were frequently reported by people with gout in the community. Gout flares were associated with reduced physical HRQoL. Almost one half of people with frequent gout flares were not receiving allopurinol, and current allopurinol use was associated with frequent gout flares, suggesting undertreated disease and suboptimal use of ULT. Determining covariate associations with flares and ineffective allopurinol use may identify means of improving treatment and reducing flares.

Topics: Adult; Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prevalence; Quality of Life; Surveys and Questionnaires

Alpinia oxyphylla is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis.. We investigated the anti-hyperuricemic effects of Alpinia oxyphylla seed extract (AE), and the underlying mechanisms of action through in vitro and in vivo studies.. We evaluated levels of uric acid in the serum and urine, the expression of renal urate transport proteins, and levels of inflammatory cytokines in potassium oxonate (PO)-induced hyperuricemic rats. Xanthine oxidase activity was analyzed in vitro, while cellular uric acid uptake was assessed in oocytes expressing the human urate transporter 1 (hURAT1). Moreover, the main components of AE were analyzed using UPLC.. In PO-induced hyperuricemic rats, 200 and 400 mg/kg of AE significantly decreased levels of uric acid in serum, while 400 mg/kg of AE increased uric acid levels in urine. AE did not inhibit xanthine oxidase in vitro; however, 1, 10, and 100 μg/ml of AE significantly decreased uric acid uptake into oocytes expressing hURAT1. Furthermore, 400 mg/kg of AE increased levels of organic anion transporter (OAT) 1 protein, while 200 and 400 mg/kg of AE decreased the protein content of urate transporter, URAT1 and inflammatory cytokines in the kidneys. Nootkatone was identified as one the main chemical components in AE from UPLC analysis.. These findings suggest that AE exerts anti-hyperuricemic and uricosuric effects, which are related to the promotion of uric acid excretion via enhanced secretion and inhibition of uric acid reabsorption in the kidneys. Thus, AE may be a potential treatment for hyperuricemia and gout.

Topics: Alpinia; Animals; China; Gout; Humans; Hyperuricemia; Kidney; Male; Organic Anion Transport Protein 1; Organic Anion Transporters; Oxonic Acid; Plant Extracts; Rats; Republic of Korea; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Cohort Studies; Febuxostat; Gout; Gout Suppressants; Humans

To determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use.. We conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined.. A total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner.. The use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes.

Topics: Aged; Allopurinol; Cardiovascular Diseases; Databases, Factual; Febuxostat; Female; Gout; Gout Suppressants; Hospitalization; Humans; Male; Retrospective Studies; Risk Factors; Taiwan

The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship.. To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout.. Population-based nested case-control study.. We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract.. The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract.. In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Case-Control Studies; Cataract; Colchicine; Databases, Factual; Female; Gout; Gout Suppressants; Humans; Logistic Models; Male; Middle Aged; National Health Programs; Risk Factors; Taiwan; Young Adult

To investigate the effects on hypercholesterolemia and hypertriglyceridemia in gouty patients receiving uric acid-lowering therapy (UALT).. A retrospective study was performed from January 2015 to December 2017 in gouty patients receiving UALT. A total of 124 gouty patients with hypercholesterolemia or hypertriglyceridemia who were administered UALT were monitored. Of the 124 patients with gout, 52 were treated with febuxostat, 29 were treated with allopurinol, and 43 were treated with benzbromarone. Cholesterol and triglyceride levels were recorded and analyzed following treatment for 8-10 weeks.. We compared the efficacy of febuxostat, allopurinol, and benzbromarone. All therapies mildly influenced serum cholesterol and triglyceride levels. Febuxostat significantly decreased cholesterol and triglyceride levels in patients who did not receive lipid-lowering therapy. Allopurinol and benzbromarone modestly decreased triglyceride levels, but cholesterol levels were unaffected.. Uric acid-lowering therapy benefits hyperlipidemia in gouty patients. Febuxostat effectively improved serum cholesterol and triglyceride levels compared to allopurinol and benzbromarone in patients with gout.

Topics: Adult; Allopurinol; Benzbromarone; Biomarkers; Cholesterol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Middle Aged; Retrospective Studies; Time Factors; Treatment Outcome; Triglycerides; Uric Acid; Uricosuric Agents

To evaluate the clinical features and risk factors for gout flare during postsurgical period in patients who were previously diagnosed with gout.. Seventy patients who had histories of gout and had been consulted in the rheumatologic clinic before surgery under general anesthesia were included. Clinical characteristics of patients who developed a postsurgical gout flare were compared with those of patients who did not develop gout flare.. Among 70 patients, 31 (44.3%) developed gout flare during the postsurgical period. Mean intervals from surgery to gout flare was 3.7 days. Flares tended to involve monoarticular joints (61.3%) and affect lower extremity joints (83.9%). Knee joints (26%) and foot joints except the first metatarsophalangeal (MTP) joint (26%) were more frequently involved than the first MTP joint (13%). Presurgical uric acid level ≥ 9 mg/dL (OR 3.77, 95% CI 1.28-11.10, p = 0.016) and amount of uric acid changes between before and after surgery (OR 1.62, 95% CI 1.21-2.18, p = 0.001) were risk factors for postsurgical gout flare. Taking allopurinol reduced the risk of postsurgical gout flare (OR 0.15, 95% CI 0.05-0.45, p = 0.001). Operation time, amount of blood loss during surgery, and surgery site were not significantly associated with postsurgical gout flare.. Adequate uric acid control before surgery could prevent the postsurgical gout flare.

Topics: Allopurinol; Blood Loss, Surgical; Female; Foot Joints; Gout; Gout Suppressants; Humans; Knee Joint; Male; Middle Aged; Operative Time; Postoperative Complications; Postoperative Period; Risk Factors; Symptom Flare Up; Uric Acid

One common ATP-binding cassette subfamily G member 2 (ABCG2) gene variant, which is encoded by the single nucleotide polymorphism (SNP) rs2231142, was identified to take an essential part in gouty arthritis. However, the relationship between rs2231142, gout comorbidities and therapeutic effect of allopurinol in Chinese Han male population is still unclear. Wherefore, this study explored into the association between ABCG2 SNP rs2231142 affecting common comorbidities and the therapeutic effect of allopurinol in Chinese Han male gout patients.. ABCG2 rs2231142 may predict the risk of kidney comorbidities for Chinese Han male gout patients, but not allopurinol response.

Topics: Adult; Aged; Alleles; Allopurinol; Asian People; ATP Binding Cassette Transporter, Subfamily G, Member 2; China; Comorbidity; Genetic Predisposition to Disease; Genotype; Gout; Humans; Male; Middle Aged; Neoplasm Proteins; Polymorphism, Single Nucleotide

Topics: Allopurinol; Febuxostat; Gout; Humans; Rheumatology; United States; United States Food and Drug Administration; Xanthine Oxidase

Topics: Allopurinol; Febuxostat; Gout; Humans; Rheumatology; United States; United States Food and Drug Administration

Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6-methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti-hyperuricemic and anti-acute gouty arthritis activities through regulating XOD, NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of anti-gout drugs targeting both innate immune sensors and XOD.

Topics: Amines; Animals; Benzoin; Benzoxazoles; Cell Line; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gout; Gout Suppressants; HEK293 Cells; Humans; Immunity, Innate; Liver; Male; Mice; Mice, Inbred Strains; Molecular Structure; Oximes; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Uric Acid; Xanthine Oxidase

Gout is a disorder that triggers a severe inflammatory reaction which generates episodes of intense pain and discomfort to the patient. Arctium minus (Hill) Bernh. (Asteraceae) is known as "burdock" and displays anti-inflammatory, antinociceptive, against rheumatic pain and radical-scavenging activities. Species of the genus Arctium have been used in assistant therapy of gout and other inflammatory processes. We investigated the antinociceptive and anti-edematogenic effects of the crude extract of A. minus seeds in an acute gout attack model induced by intra-articular injection of monosodium urate (MSU) crystals in adult male Swiss mice (25-30 g). The crude extract of A. minus (100 mg/kg, p.o.) reduced the mechanical allodynia induced by the injection of MSU (1.25 mg/site, i.a.) from 4 until 8 h after its administration. A. minus seeds crude extract prevented mechanical allodynia at doses of 30 and 100 mg/kg, but not 10 mg/kg. Allopurinol (10 µg/mL) and A. minus crude extract (10-300 µg/mL) inhibited the xanthine oxidase activity in vitro. The A. minus seeds crude extract did not cause adverse effects since did not change the toxicological parameters evaluated. A. minus crude extract can be used as an assistant therapy of gout pain, supporting its traditional use, without causing adverse effects.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arctium; Disease Models, Animal; Edema; Gout; Hyperalgesia; Inflammation; Male; Mice; Plant Extracts; Xanthine Oxidase

Topics: Allopurinol; Benzbromarone; Databases, Factual; Febuxostat; Gout; Gout Suppressants; Humans; Republic of Korea; Uric Acid

Dual-urate-lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosuric agents can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono- and dual-ULTs.. The impact of poor medication adherence was studied using two-compartment pharmacokinetic (PK) models based on published evidence, and a semi-mechanistic four-compartment pharmacodynamic (PD) model. The PKPD model was used to simulate mono and dual-ULT in gout patients with either under-excretion (lowered clearance) or overproduction of uric acid, with suboptimal adherence modelled as either a single drug holiday of increasing duration or doses taken at random.. Simulation results showed a surge in urinary uric acid occurring when dosing is restarted following missed doses. For under-excreters taking a 20-day drug holiday, the addition of 200 mg (or 400 mg) lesinurad to 80 mg febuxostat increased the percentage of patients experiencing hyperuricosuria from 0% to 1.4% (or 3.1%). In overproducers, restarting ULTs following drug holidays of more than 5 days leads to over 60% of patients experiencing hyperuricosuria.. Suboptimal medication adherence may compromise the safety and efficacy of mono- and dual-ULTs, especially in patients with gout resulting from an overproduction of uric acid. Clinicians and pharmacists should consider counselling patients with respect to the risks associated with partial adherence, and offer interventions to improve adherence or tailor treatments, where appropriate.

Topics: Computer Simulation; Drug Therapy, Combination; Febuxostat; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Models, Biological; Risk Assessment; Thioglycolates; Treatment Outcome; Triazoles; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Double-Blind Method; Gout; Humans; Standard of Care; Thioglycolates; Triazoles

Topics: Allopurinol; Double-Blind Method; Gout; Humans; Standard of Care; Thioglycolates; Triazoles

Metabolic syndrome and obesity are linked with hyperuricemia, and it has also been proposed that oxidative stress associated with hyperuricemia may promote benign prostatic hyperplasia (BPH). However, it is currently unknown whether use of antihyperuricemic medication is associated with risk of developing BPH. We studied the association between BPH and use of antihyperuricemic allopurinol in a Finnish population-based cohort.. The study cohort consisted of 74,754 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Information on gout and BPH medication usage (5α-reductase inhibitors, 5ARIs) during 1996-2014 was obtained from the National medication reimbursement database. Information on BPH diagnoses from in- and outpatient hospital visits and BPH-related surgery was obtained from the National Health Care Registry. Men with a record of BPH at baseline was excluded. We used Cox regression to analyze risk of starting BPH medication, having a recorded diagnosis or undergoing BPH surgery by allopurinol use with adjustment for age and simultaneous use of statins, antidiabetic or antihypertensive drugs and aspirin or other NSAIDs. Medication use was analyzed as a time-dependent variable to minimize immortal time bias.. Men using allopurinol had a decreased risk for all three BPH endpoints: BPH medication (HR 0.81; 95% CI 0.75-0.88), BPH diagnosis (HR 0.78; 95% CI 0.71-0.86) and BPH-related surgery (HR 0.67; 95% CI 0.58-0.76) after multivariable adjustment. The risk association did not change by cumulative use. The risk decrease disappeared after 1-2 years lag time. Only BMI modified the risk association; the risk decrease was observed only among men with BMI above the median (27.3 kg/m. We found that allopurinol use is associated with lowered risk of BPH medication, diagnosis and surgery. A possible explanation could be antioxidative effects of urate-lowering allopurinol.

Topics: Aged; Allopurinol; Cohort Studies; Finland; Free Radical Scavengers; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prostatic Hyperplasia; Risk Assessment; Risk Factors

Topics: Allopurinol; Drug Combinations; Drug Interactions; Gout; Gout Suppressants; Humans; Hyperuricemia; Organic Anion Transporters; Organic Cation Transport Proteins; Thioglycolates; Triazoles; Xanthine Oxidase

Topics: Aged; Allopurinol; Cardiovascular Diseases; Gout; Humans; Probenecid; Risk Factors

Patients with gout are at an increased risk of cardiovascular (CV) disease including myocardial infarction (MI), stroke, and heart failure (HF).. The authors conducted a cohort study to examine comparative CV safety of the 2 gout treatments-probenecid and allopurinol-in patients with gout.. Among gout patients ≥65 years of age and enrolled in Medicare (2008 to 2013), those who initiated probenecid or allopurinol were identified. The primary outcome was a composite CV endpoint of hospitalization for MI or stroke. MI, stroke, coronary revascularization, HF, and mortality were assessed separately as secondary outcomes. The authors estimated the incidence rate and hazard ratio of the primary and secondary outcomes in the 1:3 propensity score-matched cohort of probenecid and allopurinol initiators.. A total of 9,722 probenecid initiators propensity score-matched to 29,166 allopurinol initiators with mean age of 76 ± 7 years, and 54% males were included. The incidence rate of the primary composite endpoint of MI or stroke per 100 person-years was 2.36 in probenecid and 2.83 in allopurinol initiators with a hazard ratio of 0.80 (95% confidence interval: 0.69 to 0.93). In the secondary analyses, probenecid was associated with a decreased risk of MI, stroke, HF exacerbation, and mortality versus allopurinol. These results were consistent in the subgroup analyses of patients without baseline CV disease or those without baseline chronic kidney disease.. In this large cohort of 38,888 elderly gout patients, treatment with probenecid appears to be associated with a modestly decreased risk of CV events including MI, stroke, and HF exacerbation compared with allopurinol.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Cohort Studies; Female; Gout; Gout Suppressants; Humans; Male; Medicare; Probenecid; Risk Factors; United States; Uricosuric Agents

Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause-specific mortality in patients with gout.. In this 10-year observational, active-comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause-specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non-escalators) over a 2-year period.. Among the 6,428 dose escalators and 6,428 matched non-escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person-years). Dose escalators experienced an increase in all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01-1.17), with the effect sizes being similar for incidence of cardiovascular-related deaths (HR 1.08, 95% CI 0.97-1.21) and cancer-related deaths (HR 1.06, 95% CI 0.88-1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular-related mortality (HR 0.93, 95% CI 0.76-1.14).. This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active-comparator design. Dose escalation was associated with a small (<10%) increase in all-cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real-life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.

Topics: Aged; Allopurinol; Cause of Death; Dose-Response Relationship, Drug; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Regression Analysis; Treatment Outcome; United States; Veterans

There are no qualitative studies of sleep in gout; the aim of this study was to examine the impact of gout on sleep.. Nine nominal groups were conducted, oversampling for African-Americans and women with gout. Patients discussed and rank-ordered their concerns.. Nine nominal groups with 46 gout patients were conducted with mean age, 61 years (s.d. 10.6) and gout duration, 14.9 years (s.d. 12); 63% were men, 46% African-American, 52% married, 46% retired and 63% were allopurinol users. The most frequently cited highly ranked concerns could be divided into three categories. The first category, character of sleep interruption, included the concerns: severe and complete sleep interruption by gout flare pain (nine groups); and inability to get rapid eye movement sleep (one group). The second category, causes of sleep interruption, included: inability to get into a comfortable position during sleep (six groups); anxiety and depression associated with severe gout pain (seven groups); sleep interruption by moderate chronic joint pain (three groups); frequent trips to the bathroom interfering with sleep (two groups); gout medication side effects (four groups); frequent trips to the emergency room (one group); joint swelling with physical/functional deficit interfering with sleep (two groups); and flare pain interfering with sleep apnoea management (two groups). The final category, consequences of sleep interruption, included: effect on daily functioning (two groups); worsens other health conditions, which then affect sleep (four groups); and cumulative effect on sleep (one group).. Gout has significant impact on sleep quantity, quality and architecture. Sleep disruption due to gout has several pathways and significant consequences.

Topics: Aged; Allopurinol; Anxiety; Depression; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Sleep; Sleep Wake Disorders

Topics: Allopurinol; Chronic Disease; Diet; Drug Combinations; Febuxostat; Gout; Gout Suppressants; Healthy Lifestyle; Humans; Patient Education as Topic; Practice Guidelines as Topic; Purines; Thioglycolates; Triazoles; Uric Acid

OMERACT proposed a set of mandatory and discretionary domains to evaluate the effect of treatment in patients with gout. To determine the percentage of improvement and the effect size 6 and 12 months after starting a proper treatment in patients with gout from our cohort (GRESGO) based on the OMERACT proposal for chronic gout. GRESGO is a cohort of consecutive, new patients with gout attending either of two dedicated clinics. This report includes 141 patients evaluated at baseline and 6 months plus 101 of them completing a 12-month follow-up in 2012. Clinical data including the OMERACT domains for chronic gout were collected at baseline and every 6 months. Treatment was prescribed by their attending physician with the purpose of getting < 6 mg/dL of seric uric acid (sUA). Most patients were males (96%) with inappropriate treatment (95%); 66% had tophi, 30% metabolic syndrome, and 32% low renal function. Mean dose of allopurinol at baseline and throughout the study went from 344 ± 168 mg/day to 453 ± 198 at 12 months. Most OMERACT domains and renal function improved significantly; 73% improved > 20% from 6 to 12 months. Greater improvement was observed in the domains: flares, index tophus size, pain, general health assessment, and HAQ score, all of them associated to lower sUA values. Chronic gout patients improve significantly in most OMERACT domains when conventional and regular treatment is indicated. sUA < 6 mg/dL is associated with greater improvement.

Topics: Adult; Allopurinol; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Kidney; Male; Mexico; Middle Aged; Time Factors; Treatment Outcome; Uric Acid

Until very recently the only therapeutic alternative for the management of patients affected by gout/hyperuricemia that did not respond to a first-line treatment based on allopurinol alone or who cannot tolerate allopurinol was febuxostat, a xanthine oxidase non-purine-selective inhibitor. Lately, however, a new therapeutic alternative has become available for the management of this pathology: lesinurad, a urate transporter inhibitor.. To objective of this study was to evaluate the cost effectiveness of lesinurad/allopurinol in comparison with febuxostat as a second-line therapeutic strategy for the management of patients affected by gout and hyperuricemia that did not respond to a first-line therapy based on allopurinol alone.. A Markov model was built based on the natural history of the pathology; patients entered the model according to their level of serum uric acid concentration and flowed across it according to their response to the therapy. The analysis was carried out considering the perspective of the Italian National Health Service on a lifetime horizon and 6-month cycles. Costs and quality-adjusted life-years (QALYs) were discounted at a 3.5% yearly rate. The results of the model were expressed in terms of incremental cost-effectiveness ratio (ICER). Both a one-way and a multi-way Monte-Carlo analysis were carried out in order to check the robustness of the results achieved.. The ICER derived from the comparison was equal to €77.53/QALY on the lifetime horizon, as there was a higher level of costs associated with the combination as compared with febuxostat (€10,658.27 vs. €10,645.87, for a differential of €12.40) and a higher level of QALYs achieved (7.77 vs. 7.61, for a differential of 0.16).. The lesinurad/allopurinol combination is recommended for the treatment of patients affected by gout/hyperuricemia in the Italian Health System as it appears to be cost effective and thus sustainable for the Italian healthcare sector.

Topics: Allopurinol; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Italy; Male; Markov Chains; Middle Aged; Models, Economic; Monte Carlo Method; Quality-Adjusted Life Years; Thioglycolates; Triazoles

Hyperuricemia and gout have become increasingly prevalent in China. Allopurinol is an effective urate-lowering therapy, but it has severe side effects. HLA-B*5801 is highly associated with the allopurinol-induced toxic epidermal necrolysis and Stevens-Johnson syndrome.. In this retrospective report, we had genotyped HLA-B*5801 in 253 cases of hyperuricemia and gout patients in a Han population in Shenzhen and analyzed the clinical management of medications.. We found 30 carriers of the HLA-B*5801 allele in 253 cases of hyperuricemia or gout patients in the population (11.9%). Allopurinol was prescribed in both HLA-B*5801-positive and HLA-B*5801-negative groups. The evaluation of four models with or without genetic screening and management of allopurinol or febuxostat indicated that the HLA-B*5801 screening had significant cost benefit for clinical management.. For appropriate management and cost-effectiveness, the HLA-B*5801 allele should be screened in all patients with hyperuricemia and gout in the Chinese population.

Topics: Adult; Allopurinol; China; Cost-Benefit Analysis; Febuxostat; Female; Gene Frequency; Genetic Testing; Gout; Gout Suppressants; HLA-B Antigens; Humans; Hyperuricemia; Male; Middle Aged; Precision Medicine; Retrospective Studies; Treatment Outcome

Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Both anti-hyperuricemia and anti-inflammation could be gout therapeutic strategies, whereas ideal drugs for gout treatment are deficient.. 4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol (CBED) was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic and anti-inflammatory activities, which was expected to be a dual inhibitor of xanthine oxidase (XOD) and NOD-like receptor protein 3 (NLRP3). This study aimed to investigate effects of CBED on XOD and NLRP3 in vitro, as well as the possible mechanisms by which CBED improved gout in vivo.. After molecular docking detection, inhibitory effects of CBED on XOD and NLRP3 were evaluated in vitro. Subsequently, hyperuricemia and acute gouty arthritis animal models were established by potassium oxonate or MSU, respectively. After CBED treatment, serum uric acid levels, synovial interleukin (IL)-1β concentrations, hepatic XOD activities, as well as synovial morphological changes were examined. More importantly, synovial expressions of NLRP3 inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 in rats were analyzed by immunofluorescence and western blot.. In vitro, CBED obviously inhibited XOD activity with an IC. CBED might serve as a dual XOD and NLRP3 inhibitor for treatment of gout.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzene Derivatives; Enzyme Inhibitors; Gout; Humans; Hyperuricemia; Inflammasomes; Liver; Male; Mice; Mice, Inbred NOD; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Uric Acid; Xanthine Oxidase

A 26-year-old man with history of extensive tophaceous gout presented to the referring facility with decreased bilateral lower extremity sensation and motor function that began acutely 1 week prior to admission and had progressed to urinary incontinence. The patient was admitted to the intensive care unit due to concern for sepsis secondary to epidural abscess. The patient was started on empiric vancomycin and cefepime. Neurosurgery did not recommend acute neurosurgical intervention given the lack of a compressive lesion. Aspiration of the paraspinal collection by interventional radiology subsequently showed crystals consistent with tophaceous gout. Given the high initial suspicion for gout and results of the paraspinal aspiration, the patient was started on prolonged steroid taper as well as allopurinol and colchicine. The patient eventually had partial neurological recovery with discharge to an inpatient rehabilitation facility for further physical therapy rehabilitation.

Topics: Adult; Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Male; Physical Therapy Modalities; Radiology, Interventional; Spinal Diseases; Steroids; Treatment Outcome

Overexpression and crystallization of uric acid have been recognized as the course of hyperuricemia and gout, which is produced via xanthine oxidase (XOD)-catalyzed oxidation of xanthine. Therefore, the medicinal therapy of hyperuricemia and gout is majorly based on the inhibition of the XOD enzymatic pathway. The spectroscopic nature of xanthine and uric acid, namely both absorption (near the ultraviolet region) and emission (non-fluorescent) characteristics, hinders optical assay development for XOD analysis. Therefore, the state-of-the-art analysis of XOD and the screening of XOD inhibitors are majorly based on chromatography. Here, we found the near ultraviolet absorption of uric acid overlapped well with the absorption of a large bandgap semiconductor quantum dots, ZnS. On the other hand, the intrinsic weak fluorescence of ZnS QDs can be substantially improved via transition metal ion doping. Therefore, herein, we developed an inner filter effect-based assay for XOD analysis and inhibitor screening with Mn-doped ZnS QDs. The phosphorescence of Mn-doped ZnS QDs could be quenched by uric acid generated from xanthine catabolism by XOD, leading to the phosphorescence turn-off detection of XOD with a limit of detection (3σ) of 0.02 U L-1. Furthermore, the existence of XOD inhibitors could inhibit the XOD enzymatic reaction, resulting in weakened phosphorescence quenching. Therefore, the proposed assay could also be explored for the facile screening analysis of XOD inhibitors, which is important for the potential medicinal therapy of hyperuricemia and gout.

Topics: Allopurinol; Biosensing Techniques; Gout; Humans; Hyperuricemia; Luminescent Measurements; Manganese; Quantum Dots; Sulfides; Xanthine Oxidase; Zinc Compounds

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Uric Acid

Urate-lowering therapy (ULT) is a recommended life-long treatment for gout patients. However, despite these recommendations, recurrent gout attacks are commonly observed in clinical practice. The purpose of this study was to assess the levels of compliance and persistence to ULT in The Netherlands, in order to reflect on the current gout care delivered by health professionals. Anonymous prescription records were obtained from IQVIA's Dutch retrospective longitudinal prescription database, containing ULT dispensing data for allopurinol, febuxostat, and benzbromarone from November 2013 to July 2017. Compliance to ULT was determined by calculating the proportion of days covered (PDC) over 12 months. Persistence over 12 months was evaluated by determining the time to discontinuation, without surpassing a refill gap of > 30 days. Association of PDC and persistence with age, gender, and first prescriber were examined using beta regression- and cox-regression models, respectively. There were 45,654 patients who met the inclusion criteria. Overall, 51.7% of the patients had a ULT coverage of ≥ 80% of the days in 1 year (PDC ≥ 0.80), and 42.7% of the patients were still persistent after 1 year. Men, older patients, and patients whose first prescriber was a rheumatologist were more persistent and had a higher PDC. Our results show that medication adherence to ULT after 1 year is suboptimal, considering that current guidelines recommend ULT as a life-long treatment. Future studies addressing the reasons for treatment cessation and improving treatment adherence seem warranted.

Topics: Adult; Aged; Allopurinol; Benzbromarone; Febuxostat; Female; General Practitioners; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Medication Adherence; Middle Aged; Netherlands; Retrospective Studies; Rheumatologists; Uricosuric Agents; Young Adult

Topics: Allopurinol; Cohort Studies; Gout; Humans

Topics: Allopurinol; Cohort Studies; Gout; Humans

Topics: Allopurinol; Budgets; Gout; Gout Suppressants; Humans; Markov Chains; Models, Econometric; Thioglycolates; Triazoles; United States

Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases. Here, two methods, pharmacophore based on ligand and pharmacophore based on receptor-ligand, were constructed by Discovery Studio. Then GOLD was used to refine the potential compounds with higher fitness scores. Finally, molecular docking and dynamics simulations were employed to analyze the interactions between compounds and protein. The best hypothesis was set as a 3D query to screen database, returning 785 and 297 compounds respectively. A merged set of the above 1082 molecules was subjected to molecular docking, which returned 144 hits with high-fitness scores. These molecules were clustered in four main kinds depending on different backbones. What is more, molecular docking showed that the representative compounds established key interactions with the amino acid residues in the protein, and the RMSD and RMSF of molecular dynamics results showed that these compounds can stabilize the protein. The information represented in the study confirmed previous reports. And it may assist to discover and design new backbones as potential XO inhibitors based on natural products.

Topics: Biological Products; Enzyme Inhibitors; Gout; Humans; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; Uric Acid; Xanthine Oxidase

Recently, the US Food and Drug Administration (FDA) issued a public safety alert, responding to the results of the now-published Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities (CARES) trial. The CARES trial showed no significant difference between allopurinol and febuxostat in the primary composite end point of cardiovascular (CV) events in subjects with gout and established CV comorbidities at baseline. However, there was a significantly increased risk of CV and all-cause mortality with febuxostat. Urate-lowering therapy (ULT) is central to the long-term management of gout, and xanthine oxidoreductase inhibitor (XOI) therapy is the consensus first-line approach. Allopurinol is generally the first XOI used, but febuxostat is an effective XOI option, and is commonly used when allopurinol is not tolerated. These data are further relevant since CV comorbidities are common in gout. Here, we examine why the CARES trial was done, and discuss other, ongoing comparative studies of febuxostat and allopurinol whose results are awaited. We assess the strengths and limitations of the CARES trial, and appraise the robustness and biologic plausibility of the results. The CARES trial does not prove that febuxostat raises CV mortality risk, but suggests greater risk with febuxostat than allopurinol. The CARES trial results do not support first-line use of febuxostat ULT, and raise questions about febuxostat placement at various pharmacologic ULT decision tree branches. Alternatives to febuxostat that are frequently effective include allopurinol dose escalation and uricosuric therapy alone or combined with allopurinol. The FDA safety alert highlights the need for shared ULT medical decision-making with gout patients, including discussion of the CV safety of febuxostat.

Topics: Allopurinol; Cardiovascular Diseases; Comorbidity; Enzyme Inhibitors; Europe; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Japan; Mortality; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration; Xanthine Oxidase

Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients. In recent years, several renal tubular urate transporter single nucleotide polymorphisms (SNPs), including those of the GLUT9, ABCG2 and URAT1 genes, have been described that influence the renal handling of uric acid and modulate serum urate levels. In the present study, we analyzed whether GLUT9, ABCG2 and URAT1 gene SNPs are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency.. Three SNPs, URAT1 rs11231825, GLUT9 rs16890979 and ABCG2 rs2231142, previously associated in our population with hyperuricemia and gout, were analyzed in 27 patients with HPRT deficiency treated with allopurinol for at least 5 years.. Patients with HPRT deficiency having allele A of rs16890979 in the GLUT9 gene present with a lower serum urate concentration at diagnosis, before allopurinol treatment is instituted, and need lower allopurinol doses to maintain serum urate levels between 268 and 446 μmol/L (4.5 and 7.5 mg/dL). No relationship between rs2231142 in the ABCG2 gene or rs11231825 in the URAT1 gene and serum urate levels or allopurinol response was found in our patients with HPRT deficiency.. GLUT9 SNPs influence the renal handling of uric acid and modulate serum urate levels and the response to treatment in patients with uric acid overproduction due to HPRT deficiency.

Topics: Adolescent; Adult; Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Biomarkers; Child; Child, Preschool; Genetic Predisposition to Disease; Glucose Transport Proteins, Facilitative; Gout; Gout Suppressants; Humans; Hyperuricemia; Lesch-Nyhan Syndrome; Middle Aged; Neoplasm Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Phenotype; Polymorphism, Single Nucleotide; Renal Elimination; Treatment Outcome; Uric Acid; Young Adult

When urate lowering therapy is indicated in patients with gout, medication adherence is essential. This study assesses non-persistence and non-adherence in patients with newly diagnosed gout, and identifies factors associated with poor medication adherence.. A retrospective data analysis was performed within the UK Clinical Practice Research Datalink (1987-2014) among incident gout patients, aged ⩾40 years and starting allopurinol (n = 48 280). The proportion of patients non-persistent (a first medication gap of ⩾90 days) after 1 and 5 years, and median time until a first 90-day gap was estimated using Kaplan-Meier statistics in those starting allopurinol and restarting after a first interruption. Non-adherence (proportion of days covered <80%) over the full observation period was calculated. Multivariable Cox- or logistic regressions assessed factors associated with non-persistence or non-adherence, respectively.. Non-persistence increased from 38.5% (95% CI: 38.1, 38.9) to 56.9% (95% CI: 56.4, 57.4) after 1 and 5 years of initiation. Median time until a first 90-day gap was 1029 days (95% CI: 988, 1078) and 61% were non-adherent. After a first gap, 43.3% (95% CI: 42.7, 43.9) restarted therapy within 1 year, yet only 52.3% (95% CI: 51.4, 53.1) persisted for 1 year. Being female and a current smoker increased the risk for non-persistence and non-adherence, while older age, overweight, receiving anti-hypertensive medication or colchicine and suffering from dementia, diabetes or dyslipidaemia decreased the risk.. Medication adherence among gout patients starting allopurinol is poor, particularly among females and younger patients and patients with fewer comorbidities. Medication adherence remains low in those reinitiating after a first gap.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Biomarkers; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Retrospective Studies; Treatment Outcome; Uric Acid

Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout.. Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score-matched cohorts of febuxostat and allopurinol initiators.. We included 24 936 febuxostat initiators propensity score-matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94-1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91-0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95% CI, 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups.. Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for >3 years versus allopurinol for >3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.

Topics: Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Cause of Death; Databases, Factual; Febuxostat; Female; Gout; Hospitalization; Humans; Hyperuricemia; Male; Medicare; Protective Factors; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States

The goal of our study was to investigate the incidence of Stevens-Johnson syndrome (SJS), the frequency of SJS diagnosis, and the association between SJS and prior use of allopurinol, carbamazepine or phenytoin. This case-control study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Controls visited the emergency department of the same hospital for trauma or fractures (excluding burns) and used allopurinol, carbamazepine or phenytoin during the past 3 months. We determined whether patients were prescribed a combination of drugs in addition to allopurinol, carbamazepine or phenytoin within the last 3 months. We identified 1 853 985 controls and 7327 SJS-diagnosed patients using the Taiwan NHIRD records for 2000-2008. Higher use of allopurinol (49.8%), carbamazepine (39.1%) or phenytoin (21.3%) was observed among patients (n = 3131) than among controls (n = 2858). The overall SJS incidence rate was 3.6/1 000 000. Drug combinations were uncommon (<10%) in patients or controls taking allopurinol. However, combination drug use exceeded 10% in patients taking carbamazepine or phenytoin. Logistic regression analysis of recent combination drug use revealed that phenobarbital, valproate, non-steroidal anti-inflammatory drugs (NSAIDs) including piroxicam and tenoxicam, and antibiotics including amoxicillin and cephalexin were strongly associated with SJS. Patients with gout or epilepsy taking allopurinol, carbamazepine or phenytoin should be evaluated carefully by physicians. Concurrent use of piroxicam, tenoxicam, phenobarbital, valproate, amoxicillin or cephalexin, in addition to carbamazepine or phenytoin, may increase the incidence of SJS.

Topics: Adult; Aged; Allopurinol; Anticonvulsants; Carbamazepine; Case-Control Studies; Drug Combinations; Epilepsy; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Phenytoin; Stevens-Johnson Syndrome; Taiwan

Gout has an increasing global prevalence. Underutilization of urate-lowering therapy (ULT) is thought to be common, via both suboptimal dosing and poor medication adherence. The aims of this study were to determine the prevalence of self-reported gout and the key predictors of ULT use in those with gout in a representative population survey in South Australia.. Data were obtained from the Spring 2015 South Australian Health Omnibus Survey, a multilevel, systematic, survey in a representative population sample involving face-to-face interviews (n = 3005). This study analyzed responses from respondents aged ≥ 25 years (n = 2531) about self-reported gout, ULT use, sociodemographic factors, lifestyle factors, and comorbidities, using survey weighting. Univariate and subsequent adjusted logistic regression analyses on self-reported gout were performed. ULT use was divided into three categories (never use, prior use, and current use) and these data were analyzed using a multinomial logistic regression model.. Self-reported gout prevalence was 6.8% (95% CI 5.8, 7.9). The mean age of respondents with gout was 64 years (standard deviation 16) and 82% were male. As expected, older age, male gender, lower socioeconomic status (SES), and higher body mass index (BMI) were associated with gout, as were high alcohol consumption, current smoking, other forms of arthritis, and hypertension or hypercholesterolemia medication, after adjustment for sociodemographic variables. Two thirds of respondents with gout reported ULT use (36% current; 29% previous) with only 55% continuing treatment. Predictors of ULT use included male gender, low SES, and concomitant cholesterol-lowering therapy. Respondents with gout with a higher BMI were more likely to remain on ULT.. Despite gout being a common, potentially disabling joint disease, only 55% of respondents with gout in this study adhered to ULT. Identification of key predictors of ULT use will provide guidance on prescribing strategy in clinical practice and on the quality of gout care in the community.

Topics: Adult; Aged; Allopurinol; Australia; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Prevalence; Surveys and Questionnaires

To assess the goals of gout treatment from a patient perspective, a convenience sample of consecutive patients with doctor-diagnosed gout seen at a community-based outpatient clinic were invited. Sex-stratified nominal groups were conducted until saturation was achieved. Responses were collected verbatim, discussed, and rank-ordered by each participant. Thirty-six patients with doctor-diagnosed gout participated in 12 nominal groups: 6 male only, 5 female only, and 1 group with both. Mean age was 61.9 years (SD, 12.3); mean gout duration was 13.3 years (SD, 12.5); 53% were men, 64% African-American, 42% retired, 47% currently married, 87% were using either allopurinol and/or febuxostat, and 40% had had no gout flares in the last 6 months. The top 5 treatment goals accounted for 91% of all votes and included the following: (1) prevent and better manage flare-ups and improve function (25%), (2) eliminate flare-ups/disease remission (30%), (3) diet and activity modification/lifestyle change (13%), (4) patient education and public awareness (12%), and (5) medication management and minimization of side effects (11%). When examining the top-rated concern for each nominal group, the first two goals were nominated by four groups each, diet/activity modification and medication management by 1 group each, and patient education by 3 groups. There were no differences evident by sex in top-ranked treatment goal. People with gout identified and rank-ordered treatment goals relevant to them. Providers of gout care need to be cognizant of these goals. Disease management concordant with these treatment goals might lead to a more satisfied, informed patient.

Topics: Allopurinol; Febuxostat; Female; Goals; Gout; Gout Suppressants; Humans; Life Style; Male; Middle Aged; Patient Education as Topic; Symptom Flare Up

Hyperurecemia is usually associated with gout and various metabolic arthritis disorders. Limited medications are available to manage such conditions. This study aimed to isolate the triterpenes constituent of the plant and to assess xanthine oxidase (XO) inhibitory and antihyperuricemic activities of Tribulus arabicus ethanolic extract, its fractions and the isolated compound using in vitro and in vivo approaches.. The ethanolic extract, fractions; n-hexane, chloroform and n-butanol and the isolated compound (ursolic acid) were evaluated in vitro for their XO inhibitory activity. Those that demonstrated significant activity were further evaluated for their antihyperuricemic activity on potassium oxonate-induced hyperuricemia in mice.. The ethanolic extract was found to be safe up to 5000 mg/kg. The extract and its n-hexane fraction exhibited significant inhibitory activity on XO, whilst only a modest reduction in the enzymatic activity was noticed with n-butanol and chloroform fractions. Furthermore, administration of the ethanolic extract at low and high doses significantly reduced serum urate levels in mice by 31.1 and 64.6% respectively. The isolated active constituent, ursolic acid, showed potent XO inhibition activity (Half maximal inhibitory concentration, IC50 = 10.3 μg/mL), and significantly reduced uric acid level in vivo by 79.9%. Virtually, the binding mode of ursolic acid with XO was determined using molecular docking simulations.. The activity of the ethanolic extract of T. arabicus and its n-hexane fraction can be attributed to the isolated compound, ursolic acid. Ursolic acid has good hypouricemic activity and therefore has high potential to be used for the treatment of gout and hyperuricemia-related diseases.

Topics: Animals; Anti-Infective Agents; Disease Models, Animal; Gout; Humans; Hyperuricemia; Mice; Molecular Docking Simulation; Plant Extracts; Tribulus; Triterpenes; Ursolic Acid; Xanthine Oxidase

Topics: Allopurinol; Biopsy; Diagnosis, Differential; Endoscopy, Digestive System; Gout; Gout Suppressants; Humans; Incidental Findings; Laryngeal Diseases; Laryngoscopy; Male; Middle Aged; Smokers

Topics: Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Gout; Humans; Neoplasm Proteins; Organic Anion Transporters; Oxypurinol; Xanthine Dehydrogenase

Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines.. To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher.. A time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis.. Allopurinol initiation at a dose of 300 mg or more per day.. Development of chronic kidney disease stage 3 or higher.. Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09).. In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Renal Insufficiency, Chronic; Young Adult

Topics: Allopurinol; Drug Evaluation; Gout; Humans; Medical Errors; Renal Insufficiency, Chronic

Topics: Aged; Allopurinol; Cardiovascular Diseases; Febuxostat; Gout; Gout Suppressants; Humans; Risk Factors; Xanthine Oxidase

Gout is a chronic disease associated with deposition of monosodium urate crystals and accompanied by diabetes, hypertension, and dyslipidemia. Hypertriglyceridemia is common among patients with gout, and fenofibrate is usually used to reduce triglyceride levels. The aim of this study is to determine the effect of uric acid reduction by fenofibrate in patients with gout administered uric acid lowering agents (viz., the xanthine oxidase inhibitors allopurinol and febuxostat). Data from 863 patients with gout were collected from electronic medical records comprising information on underlying diseases, laboratory findings, and drug histories. Among all the patients, 70 (8.11%) took fenofibrate with allopurinol or febuxostat. Male and young patients took fenofibrate more frequently, and hypertension was less frequent in patients administered xanthine oxidase inhibitors and fenofibrate than in those administered only xanthine oxidase inhibitors. After the treatment, serum uric acid levels more significantly decreased (-1.81 ± 2.41 vs. -2.40 ± 2.28 mg/dL, p = 0.043) in patients with fenofibrate cotreatment, than in those administered allopurinol or febuxostat alone. The effect of uric acid reduction was larger (b = -1.098, p < 0.001) in patients taking glucocorticoids than in those administered other treatments. There was no difference in the levels of creatinine, blood urea nitrogen, and aminotransferases between patients treated with and without fenofibrate. Fenofibrate additionally reduced uric acid levels without showing any change in the results of renal or liver function tests, suggesting that the addition of fenofibrate is a reasonable option for treating gout in patients having high triglyceride levels.

Topics: Adult; Aged; Drug Interactions; Enzyme Inhibitors; Female; Fenofibrate; Gout; Humans; Kidney; Liver; Male; Middle Aged; Uric Acid; Xanthine Oxidase

Conflicting data in the literature raise the question whether gout, independent of its treatment, increases the risk of dementia in the elderly. Our objective was to assess whether gout in older adults is associated with the risk of incident dementia.. We used the 5% Medicare claims data for this observational cohort study. We used multivariable-adjusted Cox proportional hazard models to assess the association of gout with a new diagnosis of dementia (incident dementia), adjusting for potential confounders/covariates including demographics (age, race, sex), comorbidities (Charlson-Romano comorbidity index), and medications commonly used for cardiac diseases (statins, beta-blockers, diuretics, and angiotensin converting enzyme (ACE)-inhibitors) and gout (allopurinol and febuxostat).. In our cohort of 1.71 million Medicare beneficiaries, 111,656 had incident dementia. The crude incidence rates of dementia in people without and with gout were 10.9 and 17.9 per 1000 person-years, respectively. In multivariable-adjusted analyses, gout was independently associated with a significantly higher hazard ratio of incident dementia, with a HR of 1.15 (95% CI, 1.12, 1.18); sensitivity analyses confirmed the main findings. Compared to age 65 to < 75 years, age 75 to < 85 and ≥ 85 years were associated with 3.5 and 7.8-fold higher hazards of dementia; hazards were also higher for females, black race or people with higher medical comorbidity.. Gout was independently associated with a 15% higher risk of incident dementia in the elderly. Future studies need to understand the pathogenic pathways involved in this increased risk.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Comorbidity; Dementia; Female; Gout; Humans; Male; Medicare; Proportional Hazards Models; Retrospective Studies; Risk Factors; United States

Gout is the most common inflammatory arthritis in the Dutch general practice population and is often managed with long-term uric acid lowering treatment. The clinical relevance of this treatment in preventing gout attacks is unclear.. What is the frequency of self-reported gout attacks and what is the effect of allopurinol use in patients diagnosed with gout in general practice?. Adult patients with a diagnostic consultation code for gout in the year 2013, 2014 or 2015 will be invited to participate in this prospective observational cohort study. Patients with a limited life expectancy will be excluded. Baseline measurements will include blood pressure, body mass index and a blood sample (estimated glomerular filtration rate, serum uric acid, cholesterol (low-density lipoprotein (LDL) and high-density lipoprotein), glucose (fasting)). At the 2-year follow-up, patients will receive questionnaires every 3 months. The questionnaires at baseline, 12 months and 24 months assess the frequency of gout attacks, the presence of tophi, comorbidity, medication use, quality of life, diet and lifestyle. The questionnaires in between only assess the frequency of gout attacks and medication use for gout. Descriptive statistics will be used to calculate the mean frequency of self-reported gout attacks during the 2-year follow-up. The propensity score for each patient being offered allopurinol is estimated and used to match patients with and without allopurinol treatment. We will compare the frequency of gout attacks in these groups using multilevel Poisson regression analyses. With this type of analysis, we can calculate the corrected estimated effect of allopurinol on gout attack frequency.. The research protocol was approved by the Medical Ethical Committee of the Erasmus Medical Centre in Rotterdam. The knowledge generated by this study will be transferred to the Dutch College of General Practitioners, conferences and to (inter)national peer-reviewed journals.. NTR6329; Pre-results.

Topics: Adult; Allopurinol; Diet; Female; General Practice; Gout; Gout Suppressants; Humans; Life Style; Male; Middle Aged; Netherlands; Patient Reported Outcome Measures; Prospective Studies; Quality of Life; Regression Analysis

Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses.. To estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY).. Treatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model.. The base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence.. The estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

Topics: Allopurinol; Cohort Studies; Cost-Benefit Analysis; Drug Therapy, Combination; Economics, Pharmaceutical; Febuxostat; Gout; Gout Suppressants; Health Care Costs; Humans; Medication Adherence; Models, Biological; Models, Economic; Quality of Life; Quality-Adjusted Life Years; Thioglycolates; Treatment Outcome; Triazoles; United Kingdom; Uric Acid

We used the 5% random Medicare claims from Americans 65 years or older from 2006-2012 to examine the association of gout with the risk of developing incident (new) depression using multivariable-adjusted Cox proportional hazards model, adjusting for demographics (age, race, sex), common cardiovascular medications, allopurinol, and febuxostat and medical comorbidity. Of the 1.69 million people, 142,596 developed depression. In multivariable-adjusted analyses, gout was independently associated with 42% higher hazard of depression in older adults, confirmed in sensitivity analyses. This finding suggests the gout patients should be screened for depression and may trigger research to assess the role of inflammation and oxidative stress pathways in older people with depression.

Topics: Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Comorbidity; Depressive Disorder; Febuxostat; Female; Follow-Up Studies; Gout; Humans; Incidence; Male; Mass Screening; Medicare; Proportional Hazards Models; Retrospective Studies; Risk; United States

Topics: Adult; Allopurinol; Clinical Trials as Topic; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Oxypurinol; Uric Acid

With the aim of finding a better xanthine oxidase inhibitor with potential anti-gout properties, the studies on the fruit of Stauntonia brachyanthera were carried out, which led to the isolation of 12 glycosides, including 4 new nor-oleanane triterpenoids. Their structures were determined by comprehensive spectroscopic (NMR and HR MS) analysis. Two compounds (4 and 11) exhibited significant inhibitory activities on xanthine oxidase with IC

Topics: Dose-Response Relationship, Drug; Enzyme Inhibitors; Fruit; Glycosides; Gout; Humans; Magnoliopsida; Molecular Structure; Structure-Activity Relationship; Xanthine Oxidase

There are no published human studies investigating whether the use of allopurinol, the most commonly used medication for the treatment of hyperuricemia in gout, the most common type of inflammatory arthritis in adults, has any beneficial effects on ventricular electrophysiology. The objective of our study was to assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA).. We used the 5% random sample of Medicare beneficiaries from 2006-2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, sex), comorbidity, cardiac medications, and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI).. Of the 28,755 episodes of new allopurinol use, 2538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, 75% had gout as the underlying diagnosis, and the mean Charlson-Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1-180 days, 151; 181 days to 2 years, 105; and > 2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76-0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1-180 days, 0.96 (95% CI, 0.85-1.08); 181 days to 2 years, 0.76 (95% CI, 0.68-0.85); and > 2 years, 0.72 (95% CI, 0.60-0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates.. Allopurinol use and use duration of more than 6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Arrhythmias, Cardiac; Comorbidity; Female; Gout; Humans; Incidence; Male; Medicare; Middle Aged; Risk Factors; Time Factors; United States

Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA).. A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLA-B*58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening. A 1-year time frame and third-party payer perspective were modeled for both the entire cohort (base-case) and for the subgroup of patients with chronic kidney disease (CKD).. The incremental cost-effectiveness ratio of genetic screening prior to ULA therapy was estimated as New Taiwan (NT) $234,610 (US$7508) per QALY gained in the base-case cohort. For patients with CKD, it was estimated as NT$230,925 (US$7390) per QALY. The study results were sensitive to the probability of benzbromarone/febuxostat-related hypersensitivity, and a negative predicted value of genotyping.. HLA-B*58:01 screening gave good value for money in preventing allopurinol-induced SCAR in patients indicated for ULA therapy. In addition to the costs of genotyping, it is important to monitor ULA safety closely in adopting HLA-B*58:01 screening in practice.

Topics: Allopurinol; Cost-Benefit Analysis; Genetic Testing; Genotype; Gout; Gout Suppressants; HLA-B Antigens; Humans; Pharmacogenetics

Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients.. We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders.. A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019).. Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Gout; Gout Suppressants; Humans; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms; Risk Factors

In 2006, recommendations about the management of gout were issued by the European League Against Rheumatism (EULAR). The objective of this work was to compare these recommendations to practice patterns of physicians working in private practices in France.. In a prospective multicenter nationwide study conducted in France, a random sample of primary-care physicians (PCPs) and private-practice rheumatologists (PPRs) was taken in 2009. Each physician included 2 consecutive patients with gout. Each patient was evaluated twice at an interval of 3-6months. Information on EULAR 2006 management modalities were collected in a standardized manner.. Of 1003 patients, 771 were evaluated twice. Allopurinol was prescribed to 75.1% of patients in all and was initiated at the first study visit in 44 patients, among whom 19 (43.2%) 19 patients received the recommended starting dosage of 100mg/day. Colchicine therapy to prevent flares was prescribed to 74.3% of patients. Of the 522 patients on allopurinol therapy at the first visit, only 34.5% had serum uric acid levels≤360μmoL/L (mean dosage, 173 mg/day). Excessive dietary intake by patients who were overweight or obese was recorded in 31.5% of patients seen by PCPs and in 19.7% of those seen by OBRs. This finding prompted the delivery of nutritional advice to 45.8% of patients. Discontinuation of excessive alcohol intake was recommended to only 10% of patients. Diuretic therapy discontinuation was feasible in 175 patients but was recommended in only 7 patients.. Differences between practice patterns and 2006 EULAR recommendations were identified. Simplifying the recommendations and teaching them during medical training and continued medical education may deserve consideration.

Topics: Allopurinol; Ambulatory Care; Colchicine; Female; France; Gout; Gout Suppressants; Health Behavior; History, 21st Century; Humans; Male; Patient Education as Topic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Primary Health Care; Professional Practice; Prospective Studies; Rheumatology; Risk Factors; Risk Reduction Behavior; Uric Acid

Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal deposition, are common in patients with chronic kidney disease (CKD). Although the presence of CKD poses additional challenges in gout management, effective urate lowering is possible for most patients with CKD. Initial doses of urate-lowering therapy are lower than in the non-CKD population, whereas incremental dose escalation is guided by regular monitoring of serum urate levels to reach the target level of <6mg/dL (or <5mg/dL for patients with tophi). Management of gout flares with presently available agents can be more challenging due to potential nephrotoxicity and/or contraindications in the setting of other common comorbid conditions. At present, asymptomatic hyperuricemia is not an indication for urate-lowering therapy, though emerging data may support a potential renoprotective effect.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Diet Therapy; Disease Management; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Symptom Flare Up; Treatment Outcome; Uric Acid

Febuxostat has currently played pivotal role in the treatment of hyperuricemia, but there is little comprehensive information for the determinants of individual difference in efficacy of febuxostat. Therefore, the present study, a retrospective investigation, was carried out to analyze the effects of patient characteristics on the efficacy of febuxostat. A total of 225 patients who were continuously prescribed the same dose of febuxostat for 8-12 weeks from the initial therapy were enrolled in the present study. The data, including patient information and laboratory data, were collected from electronic medical records. Serum urate lowering effects of febuxostat were evaluated by calculating the change in serum urate level at baseline and at 8-12 weeks after starting febuxostat. The multiple regression analysis showed the change in serum urate level was significantly lower in male patients and in those with a lower baseline serum urate level, higher previous dose of allopurinol, lower dose of febuxostat and lower body surface area-unadjusted estimated glomerular filtration rate. Concomitantly administered drugs did not show a significantly influence on the efficacy of febuxostat. In conclusion, it should be noted that the serum urate lowering efficacy of febuxostat may decrease in patients with a higher previous dose of allopurinol, renal impairment or male patients. The basic findings of the present study are believed to contribute to the proper use of febuxostat.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Febuxostat; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Uric Acid

Topics: Allopurinol; Genetic Testing; Gout; Gout Suppressants; Humans; Uric Acid

To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly.. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models.. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings.. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol.

Topics: Administrative Claims, Healthcare; Aged; Aged, 80 and over; Allopurinol; Comparative Effectiveness Research; Febuxostat; Female; Gout; Gout Suppressants; Humans; Incidence; Kidney Diseases; Male; Medicare; Propensity Score; Proportional Hazards Models; Retrospective Studies; United States

The aim of this study was to quantify the value of conducting additional research and reducing uncertainty regarding the cost effectiveness of allopurinol and febuxostat for the management of gout.. We used a previously developed Markov model that evaluated the cost effectiveness of nine urate-lowering strategies: no treatment, allopurinol-only fixed dose (300 mg), allopurinol-only dose escalation (up to 800 mg), febuxostat-only fixed dose (80 mg), febuxostat-only dose escalation (up to 120 mg), allopurinol-febuxostat sequential therapy fixed dose, allopurinol-febuxostat sequential therapy dose escalation, febuxostat-allopurinol sequential therapy fixed dose, and febuxostat-allopurinol sequential therapy dose escalation. Each strategy was evaluated over the lifetime of a hypothetical gout patient. We calculated population expected value of perfect information (EVPI). We used a linear regression meta-modeling approach to calculate population expected value of partial perfect information (EVPPI), and a Gaussian approximation to calculate the population expected value of sample information for parameters (EVSI) and the expected net benefit of sampling (ENBS) for four potential study designs: (1) an allopurinol efficacy trial; (2) a febuxostat efficacy trial; (3) a prospective observational study evaluating health utilities; and (4) a comprehensive study evaluating the efficacy of allopurinol and febuxostat and health utilities. A 5-year decision time horizon was used in the base-case analysis.. EVPI varied by a decision maker's willingness-to-pay (WTP) per quality-adjusted life-year (QALY) and was $US900 million for WTP of $US60,000 per QALY. Population EVPPI was highest across all WTP values for study design #4. For study design #4 and a WTP of $US60,000 per QALY, the optimal sample size was 735 patients per study arm.. Future studies are needed to evaluate the effectiveness of allopurinol and febuxostat dose escalation.

Topics: Allopurinol; Cost-Benefit Analysis; Drug Administration Schedule; Febuxostat; Gout; Humans; Markov Chains; Models, Economic; Research Design

Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes.. The aim of this study was to examine associations of patient and provider factors with optimal gout management.. Linking longitudinal health and pharmacy dispensing records to questionnaire data, we assessed patient and provider factors among 612 patients with gout receiving allopurinol during a recent 1-year period. Associations of patient (medication adherence and patient activation) and provider factors (dose escalation, low-dose initiation, and anti-inflammatory prophylaxis) with serum urate (SU) goal achievement of less than 6.0 mg/dL were examined using multivariable logistic regression. Medication adherence was assessed as a mediator of these factors with goal achievement.. A majority of patients (63%) were adherent, whereas a minority received dose escalation (31%). Medication adherence was associated with initiation of daily allopurinol doses of 100 mg/d or less (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.20-2.76). In adjusted models, adherence (OR, 2.35; 95% CI, 1.50-3.68) and dose escalation (OR, 2.48; 95% CI, 2.48-4.25) were strongly associated with SU goal attainment. Low starting allopurinol dose was positively associated with SU goal attainment (OR, 1.11; 95% CI, 1.02-1.20) indirectly through early adherence, but also had a negative direct association with SU goal attainment (OR, 0.21; 95% CI, 0.12-0.37).. Medication adherence and low starting dose combined with dose escalation represent promising targets for future gout quality improvement efforts. Low starting dose is associated with better SU goal attainment through increased medication adherence, but may be beneficial only in settings where appropriate dose escalation is implemented.

Topics: Aged; Allopurinol; Clinical Pharmacy Information Systems; Disease Management; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gout; Gout Suppressants; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Patient Outcome Assessment; Surveys and Questionnaires; United States; Uric Acid

Topics: Aged, 80 and over; Allopurinol; Colchicine; Enzymes, Immobilized; Gout; Gout Suppressants; Humans; Male; Patient Selection; Polyethylene Glycols; Treatment Outcome; Urate Oxidase

Uric acid (UA) is an end product of purine metabolism by the enzyme xanthine oxidase (XOD). Hyperuricemia is characterized by the accumulation of serum UA and is an important risk factor for gout and many chronic disorders. XOD inhibitors or uricase (catalyzes UA to the more soluble end product) can prevent these chronic diseases. However, currently available hypouricemic agents induce severe side effects. Therefore, we developed new microbial fermented extracts (MFEs) with substantial XOD inhibition activity from Lactobacillus (MFE-21) and Acetobacter (MFE-25), and MFE-120 with high uricase activity from Aspergillus. The urate-lowering effects and safety of these MFEs were evaluated. Our results showed that MFE-25 exerts superior urate-lowering effects in the therapeutic model. In the preventive model, both MFE-120 and MFE-25 significantly reduced UA. The results of the safety study showed that no organ toxicity and no treatment-related adverse effects were observed in mice treated with high doses of MFEs. Taken together, the results showed the effectiveness of MFEs in reducing hyperuricemia without systemic toxicity in mice at high doses, suggesting that they are safe for use in the treatment and prevention of hyperuricemia.

Topics: Animals; Fermentation; Gout; Gout Suppressants; Hyperuricemia; Mice; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Biomarkers; Drug Combinations; Gout; Gout Suppressants; Humans; Hyperuricemia; Thioglycolates; Treatment Outcome; Uric Acid; Uricosuric Agents

Despite guidance on appropriate initiation, urate-lowering therapy is prescribed for only a minority of patients with gout. Electronic health records for 8,142 patients with gout were used to investigate the effect of age, sex, comorbidities, number of consultations, and meeting internationally agreed eligibility criteria on time to allopurinol initiation. Time to first prescription was modeled using multilevel Cox proportional hazards regression. Allopurinol initiation was positively associated with meeting eligibility criteria at diagnosis of gout, but negatively associated with becoming eligible after diagnosis. Managing gout as a chronic disease, with regular reviews to discuss allopurinol treatment, may reduce barriers to treatment.

Topics: Aged; Allopurinol; Comorbidity; Electronic Health Records; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Primary Health Care; Proportional Hazards Models; Time-to-Treatment; United Kingdom

Many patients fail to achieve the recommended serum urate (SU) target (<6 mgdl

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; ATP Binding Cassette Transporter, Subfamily G, Member 2; Biomarkers; Female; Gene Frequency; Genotype; Gout; Gout Suppressants; Humans; Logistic Models; Male; Middle Aged; Neoplasm Proteins; Odds Ratio; Oxypurinol; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Treatment Outcome; Uric Acid; Young Adult

To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use.. We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson-Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes.. Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1-199 mg/day, allopurinol dose of 200-299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and ≥300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5-1 year, 1.00 (0.88, 1.15); >1-2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol ≥300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively.. Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined.

Topics: Acute Kidney Injury; Administrative Claims, Healthcare; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Incidence; Kidney Failure, Chronic; Male; Medicare; Protective Factors; Retrospective Studies; Time Factors; United States

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Kidney; Uric Acid

Topics: Aged; Allopurinol; Chronic Disease; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Male

Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that are linked to infection status, controlling for length of follow-up.. A retrospective, case-control study (N = 2212) using de-identified patient health claims information from a commercially insured, U.S. dataset representing 15 million patients annually (from January 1, 2007 to December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test, and multivariate logistic regression were used.. Male gender (OR = 1.42, p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38, p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = 0.002) and colchicine (p = 0.006); no significant difference was found for the use of specific disease-modifying anti-rheumatic drugs and TNF-α inhibitors.. High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken.

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Shoulder; Case-Control Studies; Comorbidity; Diabetes Mellitus; Female; Glucocorticoids; Gout; Gout Suppressants; HIV Infections; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Logistic Models; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Neoplasms; Obesity; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prednisone; Prosthesis-Related Infections; Retrospective Studies; Risk Factors; Sex Factors; Shoulder Joint; Surgical Wound Infection

It remains unclear why the dose of xanthine oxidase inhibitors (XOI) allopurinol or febuxostat varies among patients though they reach similar serum uric acid (SUA) goal. We pursued genomic sequencing of XOI metabolism and clearance genes to identify single-nucleotide polymorphisms (SNPs) relate to differences in XOI dose. Subjects with a diagnosis of Gout based on the 1977 American College of Rheumatology Classification Criteria for the disorder, who were on stable doses of a XOI, and who were at their goal SUA level, were enrolled. The primary outcome was relationship between SNPs in any of these genes to XOI dose. The secondary outcome was relationship between SNPs and change in pre- and post-treatment SUA. We enrolled 100 subjects. The average patient age was 68.6 ± 10.6 years old. Over 80% were men and 77% were Caucasian. One SNP was associated with a higher XOI dose: rs75995567 (p = 0.031). Two SNPs were associated with 300 mg daily of allopurinol: rs11678615 (p = 0.022) and rs3731722 on Aldehyde Oxidase (AO) (His1297Arg) (p = 0.001). Two SNPs were associated with a lower dose of allopurinol: rs1884725 (p = 0.033) and rs34650714 (p = 0.006). For the secondary outcome, rs13415401 was the only SNP related to a smaller mean SUA change. Ten SNPs were identified with a larger change in SUA. Though multiple SNPs were identified in the primary and secondary outcomes of this study, rs3731722 is known to alter catalytic function for some aldehyde oxidase substrates.

Topics: Acute Disease; Aged; Allopurinol; Cohort Studies; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Kidney; Uric Acid

With the prevalence of and hospitalizations for gout increasing, optimizing care for patients with gout is imperative. The 2012 American College of Rheumatology gout guidelines emphasize that timely monitoring is key to achieving serum urate (SUA) goals. Few studies have examined this metric following the 2012 update, and to our knowledge, none have examined a veteran population.. To evaluate adherence to urate-lowering therapy (ULT) monitoring guidelines in a veteran population.. This is a single-center, multisite, retrospective chart review of US veterans receiving ULT for gout within the VA (Veterans Affairs) Tennessee Valley Healthcare System from January 1, 2013, to June 30, 2015. The primary end point was percentage of patients with a SUA within 6 months of initial xanthine oxidase inhibitor prescription. Secondary end points included percentage of patients with SUA <6 mg/dL and percentage of patients with uptitration following SUA above goal.. A total of 601 patients met inclusion criteria for the study; after application of exclusion criteria, 505 were analyzed. Of these, 295 patients (58%) did not have a SUA drawn within 6 months, and 162 patients (32%) reached the end of the study period without SUA measured. Of 226 patients with SUA above goal on initial check, 64 (28%) had timely dose adjustment, whereas 143 patients (63%) had no adjustment. A total of 161 patients (32%) had a SUA at goal within the study period.. Rates of ULT monitoring at a major VA medical center were suboptimal, and improved adherence to guideline recommendations is needed.

Topics: Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Drug Monitoring; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Retrospective Studies; Rheumatology; Tennessee; Uric Acid; Veterans; Xanthine Oxidase

Gout is associated with cardiovascular diseases, and systemic inflammation has a role in this. CXCL8 (interleukin-8) levels were increased in synovial fluid of gout patients, and in serum in gout patients irrespective of their disease activity. We hypothesized that the well-known cardiovascular protective effects of allopurinol could be related to effects of this drug on CXCL8 levels.. Patients with a crystal proven gout diagnosis, who newly started allopurinol treatment, were included in this prospective cohort study. After evaluation at baseline for cardiovascular diseases, tophi, uric acid, CRP and CXCL8 serum levels, patients were followed for changes in uric acid and CXCL8 levels. A subgroup analysis was performed in 10 patients with the longest follow-up period and at least 4 assessments of serum uric acid and CXCL8.. Sixty patients were included, and patients known with cardiovascular diseases at baseline had significantly higher CXCL8 and uric acid levels (P<0.01). In the whole group, median CXCL8 levels had not decreased after a median (IQR) follow-up of 27 (12-44) weeks (P=0.66). In the subgroup analysis in 9 out of 10 patients, CXCL8 levels showed a slight decrease, sometimes after an initial increase after a median (IQR) follow-up of 51 (45-60) weeks.. This pilot study indicates that higher CXCL8 levels were associated cardiovascular diseases in gout patients. Short-term use of allopurinol does not decrease CXCL8 levels in gout patients, but longer use possibly does. Further studies are warranted to establish the potential mechanisms of treatment and effects on CXCL8 levels.

Topics: Adult; Allopurinol; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Female; Gout; Gout Suppressants; Humans; Incidence; Interleukin-8; Male; Middle Aged; Pilot Projects; Prognosis; Prospective Studies; Reference Values; Risk Assessment; Statistics, Nonparametric; Treatment Outcome

Positive HLA-B*5801 carriers are at greater risk of experiencing rare but severe allopurinol hypersensitivity syndrome (AHS) [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)]; however, HLA-B*5801 prevalence and AHS risk vary by race/ethnicity. We evaluated the cost-effectiveness of HLA-B*5801 testing according to race/ethnicity in the United States.. We determined the cost-effectiveness of universal testing for HLA-B*5801 compared to no testing prior to the initiation of allopurinol per US major race/ethnicity groups. Using US-specific data, SJS/TEN risks and HLA-B*5801 prevalences were modeled per race/ethnicity (i.e., 1/3846 and 0.7% among Caucasians and Hispanics, 1/735 and 3.8% among African Americans, and 1/336 and 7.4% among Asians, respectively). Those who tested positive for HLA-B*5801 received febuxostat. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime.. Compared to no testing, universal testing for HLA-B*5801 costs more and was more effective for all races/ethnicities. The ICERs varied substantially across racial/ethnic groups, following their HLA-B*5801 prevalences. HLA-B*5801 testing was cost-effective for African Americans (ICER $83,450) and Asians (ICER $64,190), but not for Caucasians or Hispanics (ICER $183,720), using accepted US willingness-to-pay threshold ($109,000/QALY). Results were robust in sensitivity analyses, except that reducing the risk of SJS/TEN by a half made testing not cost-effective for all races/ethnicities.. Testing for HLA-B*5801 prior to allopurinol initiation is cost-effective for Asians and African Americans, but not for Caucasians or Hispanics in the United States. Reducing AHS risk by other predictive measures could make HLA-B*5801 testing not cost-effective even among Asians and Blacks.

Topics: Allopurinol; Asian; Black or African American; Cost-Benefit Analysis; Female; Genetic Markers; Genetic Testing; Gout; Gout Suppressants; HLA-B51 Antigen; Humans; Male; Risk Factors; Sensitivity and Specificity; Stevens-Johnson Syndrome; United States; Uric Acid

To evaluate and compare the safety and efficacy of three urate lowering agents: febuxostat, allopurinol, and benzbromarone, when used to treat Chinese gout patients.. A total of 120 patients treated in our department from November 2011 to December 2014 were randomly selected and divided into four groups: febuxostat (40 mg per day), febuxostat (80 mg per day), allopurinol (100 mg, 3 × per day) or benzbromarone (50 mg per day), (n = 30 patients/group). The serum uric acid (UA) concentrations of the patients in each group were recorded and compared from week 2 through week 24 after the treatments, and all adverse events were evaluated to determine the safety of the various treatment regimens.. Treatment with febuxostat (40 mg) significantly reduced serum UA levels to those achieved with allopurinol or benzbromarone treatment. The treatment with febuxostat (80 mg) produced the best therapeutic effect and achieved the targeted UA level as early as week 2. However, the total number of patients experiencing adverse events was significantly higher in the febuxostat 80-mg group. The incidences of abnormal liver function, hyperlipidemia, and gout flare were higher in both febuxostat treatment groups. The allopurinol group had a higher incidence of hypersensitivity, and the benzbromarone group had a higher incidence of renal dysfunction.. Chinese patients treated with the 40-mg dose of febuxostat experienced a treatment effect and total rate of adverse events similar to those produced by allopurinol or benzbromarone. To achieve a better therapeutic effect, the dose of febuxostat can be elevated to 80 mg per day; however, patients receiving the higher dose must be closely monitored for signs of liver dysfunction. Febuxostat is an alternative treatment for Chinese gout patients who are at a much higher risk for severe cutaneous adverse reactions as well as for patients with a history of kidney stones.
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Topics: Adult; Allopurinol; Asian People; Benzbromarone; Biomarkers; China; Drug Dosage Calculations; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome; Uric Acid

Topics: Allopurinol; Double-Blind Method; Gout; Humans; Thioglycolates; Triazoles

Topics: Allopurinol; Double-Blind Method; Gout; Humans; Reward; Thioglycolates; Triazoles

Topics: Allopurinol; Double-Blind Method; Gout; Humans; Standard of Care; Thioglycolates; Triazoles

Gout is increasingly recognized as the most common form of inflammatory arthritis worldwide; however, no Canadian data on the disease burden of gout are available. We estimated the prevalence, incidence, prescription patterns, and comorbidity burden of gout in an entire Canadian province [British Columbia (BC)] over the last decade.. We utilized PopulationData BC, a province-wide database, to estimate temporal trends in the prevalence and incidence of gout from 2000 to 2012, as well as according to age category. Annual estimates were age-sex-standardized using 2012 as the reference. We also examined annual trends in prescription patterns of common gout medications and assessed the comorbidity burden among gout patients in 2012.. The 2012 prevalence of gout was 3.8% among the overall population, and the incidence rate was 2.9 per 1000 person-years. Both gout prevalence and incidence increased substantially over the study period. This burden additionally increased according to age category, affecting over 8% of those ages 60-69 years in 2012. Approximately 22% of gout patients received a prescription for urate-lowering therapy (ULT), which remained stable over the study period, while colchicine and oral glucocorticoid use both increased modestly. By 2012, 72%, 52%, and 18% of prevalent gout patients had been diagnosed with hypertension, hyperlipidemia, and diabetes, respectively.. The burden of gout in BC, Canada, is substantial, and both the prevalence and incidence have increased over the past decade, while prescription of ULT remains low. These data support the need to improve gout prevention and care.

Topics: Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; British Columbia; Colchicine; Comorbidity; Diabetes Mellitus; Febuxostat; Female; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Middle Aged; Population Growth; Prevalence; Probenecid; Sulfinpyrazone; Uricosuric Agents

Gout is a painful disorder which does not have an efficient delivery system for its treatment.. Development and in vitro, in vivo evaluation of allopurinol-loaded nonionic surfactant-based niosomes was envisaged.. Niosomes were prepared with Span 20 and Tween 20 (1:1 molar ratio) using ether injection method. The formulations were screened for entrapment efficiency, particle size analysis, zeta potential, release kinetics, in vivo activity, and stability studies.. Stable, spherical vesicles of average particle size 304 nm with zeta-potential and entrapment efficiency of 22.2 mV and 79.44 ± 0.02%, respectively, were produced. In vitro release study revealed 82.16 ± 0.04% release of allopurinol within 24 h. The niosomal formulation was further evaluated for its antigout potential in monosodium urate (MSU) crystal induced gout animal model. The formulation demonstrated significant uric acid level reduction and enhanced antigout activity when compared with the pure allopurinol.. The better antigout activity displayed by niosomal formulation could be attributed to sustained release of drug, higher drug solubility within biological fluids, better membrane interaction, smaller size, and presence of cholesterol and surfactant.. This study reveals that niosomes can be an efficient delivery system for the treatment of gout.

Topics: Administration, Oral; Allopurinol; Animals; Disease Models, Animal; Drug Delivery Systems; Gout; Hexoses; Liposomes; Particle Size; Polysorbates; Rabbits; Surface Properties; Uric Acid

Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites.. Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities.. Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice.. HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts.. The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

Topics: Animals; Anti-Inflammatory Agents; Asteraceae; Brazil; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Disease Models, Animal; Edema; Ethanol; Furans; Gout; Gout Suppressants; Hyperuricemia; Indomethacin; Inflammation; Male; Medicine, Traditional; Mice; Plant Components, Aerial; Plant Extracts; Seasons; Sesterterpenes; Xanthine Oxidase

To assess the proportion of patients with gout who achieve target serum urate levels, the drug regime required and the reasons for failing to do so.. We reviewed the files of all patients with gout who presented to a gout-oriented rheumatology practice between January 2010 and September 2014.. Two hundred and thirty patients agreed to commence urate lowering therapy (ULT); 73% achieved their urate target, including 74% with non-tophaceous gout (target ≤ 0.36 mmol/L) and 71% with tophi (target ≤ 0.30 mmol/L). Of the 62 who failed to reach target, in 61 it was due to non-adherence and in one due to inefficacy.. Adherence remains the major challenge to successful long-term gout management.

Topics: Aged; Allopurinol; Biomarkers; Drug Substitution; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Medical Audit; Medication Adherence; Practice Guidelines as Topic; Probenecid; Retrospective Studies; Rheumatology; Time Factors; Treatment Outcome; Uric Acid

Few studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes.. We used the 2007-2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders.. There were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association.. Current allopurinol use protected against the occurrence of acute cardiovascular events in patients with gout and diabetes. The underlying mechanisms for this potential cardio-protective effect of allopurinol need further exploration.

Topics: Acute Disease; Aftercare; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Diabetes Mellitus; Female; Free Radical Scavengers; Gout; Humans; Male; Middle Aged; Morbidity; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Survival Rate; United States

With the aim of finding more potential anti-gout compounds from natural resources, a phytochemical study on the leaves of Stauntonia brachyanthera was carried out, which led to the isolation of 11 nor-oleanane triterpenoids, including 4 new ones. Their structures were determined by the comprehensive 1D, 2D NMR, HRMS, and HPLC analysis after acid hydrolysis. Brachyantheraoside B4 (3) and 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl-30-norolean-12,20(29)-dien-28-oic acid (8) exhibited significant inhibitory activities on xanthine oxidase with IC50 values of 0.20 and 18.5μM, respectively. Brachyantheraoside C2 (2) also showed moderate effects on XO. A primary structure-activity relationship was also summarized, which revealed the anti-gout abilities of three nor-oleanane triterpenoids and their potential possibilities as the candidate compounds for the treatment of gout. The discovery of nor-oleanane triterpenoids also widens people's idea for the study of anti-gout agents and promotes the comprehensive development of S. brachyanthera.

Topics: Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Gout; Humans; Magnoliopsida; Molecular Structure; Oleanolic Acid; Plant Leaves; Structure-Activity Relationship

Xanthine oxidase (XO) is an important target for the treatment of hyperuricemia and gout. Based on the two known non-purine xanthine oxidase inhibitors, febuxostat and topiroxostat, 14 oxadiazole derivatives have been designed and synthesized. These compounds have been evaluated against XO and five of them exhibited significant inhibitory activities at the concentrations below 10 μmol·L(-1).

Topics: Drug Design; Enzyme Inhibitors; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Oxadiazoles; Xanthine Oxidase

The purpose of this study is to investigate the effect of urate-lowering therapies (ULTs) on renal uric acid excretion in gout patients. This prospective observational study involved 106 primary gout patients and 51 healthy controls. Gout patients received ULT with either xanthine oxidase inhibitors or the uricosuric agent benzbromarone. Parameters such as 24-h urinary uric acid, creatinine clearance, uric acid clearance, glomerular filtration load of uric acid, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to urinary creatinine ratio were used to evaluate the pre- and post-treatment renal capacity for uric acid clearance in gout patients and were compared with the values in the healthy controls. Compared to healthy controls, gout patients had higher glomerular filtration load of uric acid and lower uric acid clearance, creatinine clearance, and fractional uric acid excretion. After ULT, both the xanthine oxidase inhibitor group and benzbromarone group patients showed reduction in glomerular filtration load of uric acid. Creatinine clearance was significantly improved in the xanthine oxidase inhibitor group. Excretion function was remarkably enhanced in patients who reached the treatment target (serum uric acid <6 mg/dl). Changes in glomerular uric acid filtration load were significantly correlated with changes in serum urate levels. Gout patients have impaired renal uric acid excretion. ULTs reduce renal urate load and enhance the renal capacity of uric acid clearance. Xanthine oxidase inhibitors showed superiority over benzbromarone in improving renal function.

Topics: Adult; Antihypertensive Agents; Benzbromarone; Case-Control Studies; Creatinine; Glomerular Filtration Rate; Gout; Humans; Hypertension; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Uric Acid; Uricosuric Agents; Xanthine Oxidase

To identify adherence and persistence levels with urate-lowering therapies using the national administrative pharmacy claim database. This was a retrospective, pharmacy claims-based analysis of dispensed anti-gout medications on the Irish national HSE-PCRS scheme database between January 2008 and December 2012. Adherence is defined by the medication possession ratio (MPR), and patients were considered to be adherent if the MPR ≥80 % (good adherers) in any given time period. Persistence was defined as continued use of therapy with no periods exceeding a refill gap of >63 days (9 weeks). Logistic regression analysis was used to predict odd ratios (OR) and 95 % confidence interval (CI) for persistence and adherence in relation to age, gender and level of comorbidity. There was a 53 % increase in the number of patients prescribed anti-gout medications between 2008 and 2012 with an increase of 27 % in the associated ingredient cost of these medications. Allopurinol accounted for 87 % of the prescribing and febuxostat accounted for a further 9 %. In patients who started on 100 mg allopurinol, only 14.6 % were titrated to the 300 mg dose. For all those initiating urate-lowering therapies, 45.8 % of patients were persistent with treatment at 6 months decreasing to 22.6 % at 12 months. In multivariate analysis, females had poorer adherence (OR = 0.83 (0.77-0.90)), and increasing age was associated with increased adherence (OR = 4.19 (2.53-6.15)) Increasing comorbidity score was associated with increased adherence and persistence at 6 months (OR = 0.68 (0.59-0.79)). Adherence with anti-gout medications in this study cohort was relatively low. Sustained treatment for gouty arthritis is essential in the prevention of serious adverse outcomes.Significance and Innovations-Poor adherence to medications prescribed to patients for the management of chronic diseases such as gout is an ongoing problem which urgently needs to be addressed.-Some of the reasons identified for poor adherence to anti-gout medications include the risk of flare of acute gout with the initiation of urate-lowering therapy (ULT), poor response to ULT and persistence of attacks of acute gout, suboptimal dosing of allopurinol therapy and intolerance of allopurinol.-The results of this study identified adherence and persistence rates of approximately 50 % at 6 months which is in line if not lower than many of the other published studies to date which have measured adherence and persistence using pharmac

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Databases, Factual; Febuxostat; Female; Gout; Gout Suppressants; Humans; Ireland; Male; Medication Adherence; Middle Aged; Retrospective Studies; Sex Factors; Uric Acid; Young Adult

Our aim is to investigate the risk association between allopurinol use and cancer incidence among gout patients using clinical evidence. Newly diagnosed male patients with gout, 20 years or older, were included after excluding those who had a diagnosis of type 2 diabetes, and were followed up for 12 years in a retrospective cohort study of one million outpatients of a national database. The gout patients were matched to male controls by age and first diagnosis date of gout disease. We then estimated the risk associations between incident cancers and duration of allopurinol use by Cox hazard regression, age-adjusted standardized incidence ratio, and incidence per 1000 person-years. A total of 24 050 gout patients and 76 129 controls were included. The incidence of all-cause cancers for gout patients and controls was 8.26 cases and 7.49 cases/1000 person-years, respectively; it was markedly increased in gout patients who used allopurinol for over 90 days. The hazard ratio of all-cause cancers was 1.21 (95% confidence interval=1.03-1.42, P=0.019) after adjustment for age and 2.26 for bladder cancer (95% confidence interval=1.32-3.87, P=0.003) on comparing those who used allopurinol for over 90 days with nonusers. Meanwhile, other cancers did not show the same significant result. We concluded that those who used allopurinol for a long duration had a higher occurrence of both bladder cancer and all-cause cancers in clinical evidence.

Topics: Adult; Allopurinol; Case-Control Studies; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Longitudinal Studies; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Taiwan; Urinary Bladder Neoplasms

Hyperuricemia/gout and atrial fibrillation (AF) are two pathological conditions that are highly prevalent in type 2 diabetes and share multiple cardiovascular risk factors. However, the relationship between elevated levels of serum uric acid and risk of AF in type 2 diabetes is currently poorly known.. We studied a hospital-based sample of 842 (male/female = 463/379) patients with type 2 diabetes discharged from our Division of Endocrinology during 2007-2011. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists.. Overall, 243 (28.9 %) patients had hyperuricemia and 91 (10.8 %) patients had persistent or permanent AF. Compared with those with normal serum uric acid levels, patients with hyperuricemia had a remarkably greater prevalence of AF (20.6 vs. 7.1 %; p < 0.001). Hyperuricemia was significantly associated with an increased risk of prevalent AF (odds ratio 3.41, 95 % CI 2.19-5.32; p < 0.001). Adjustments for age, sex, smoking, hemoglobin A1c, hypertension status, chronic kidney disease, chronic obstructive pulmonary disease and previous histories of hyperthyroidism, ischemic heart disease and valvular heart diseases did not weaken this association (adjusted-odds ratio 6.27, 95 % CI 1.82-21.5; p < 0.01).. These results indicate that hyperuricemia is associated with an increased prevalence of AF in hospitalized patients with type 2 diabetes, independently of multiple risk factors and potential confounders.

Topics: Aged; Aged, 80 and over; Allopurinol; Atrial Fibrillation; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Electronic Health Records; Female; Gout; Gout Suppressants; Hospitalization; Hospitals, University; Humans; Hyperuricemia; Italy; Male; Middle Aged; Prevalence; Retrospective Studies; Risk; Uric Acid

The objective of the study is to examine the impact of gout and its treatments on health-related quality of life (HRQOL) using focus group interviews. From the baseline phase of a cohort study of HRQOL in gout, 17 participants (15 males, mean age 71 years) with varying attack frequency and treatment with and without allopurinol participated in one of four focus group interviews. All interviews were audio-recorded and transcribed verbatim. Data was analysed thematically. Physical and psychosocial HRQOL in gout was affected by characteristics of acute gout (particularly the unpredictable nature of attacks, location of joint involved in an attack, pain and modifications in lifestyle), lack of understanding of gout by others (association with unhealthy lifestyle, symptoms ridiculed as non-severe and non-serious) as well as participants (not considered a disease) and the lack of information provided by physicians (about causes and pharmacological as well as non-pharmacological treatments of gout). Participants emphasised the impact of acute attacks of gout and prioritised dietary modifications and treatment of acute attacks over long-term urate-lowering therapy. Characteristics of acute gout, lack of understanding and information about gout and its treatments perpetuate poor HRQOL. HRQOL (maintenance of usual diet and reduced frequency of attacks) was associated with urate-lowering treatment. Better patient, public and practitioner education about gout being a chronic condition associated with co-morbidities and poor HRQOL may improve understanding and long-term treatment of gout.

Topics: Aged; Aged, 80 and over; Allopurinol; Attitude to Health; Female; Focus Groups; Gout; Humans; Life Style; Male; Middle Aged; Qualitative Research; Quality of Life; Social Stigma

The primary aim of this research was to predict the allopurinol maintenance doses required to achieve the target plasma urate of ≤0.36 mmol l(-1) .. A population analysis was conducted in nonmem using oxypurinol and urate plasma concentrations from 133 gout patients. Maintenance dose predictions to achieve the recommended plasma urate target were generated.. The urate response was best described by a direct effects model. Renal function, diuretic use and body size were found to be significant covariates. Dose requirements increased approximately 2-fold over a 3-fold range of total body weight and were 1.25-2 fold higher in those taking diuretics. Renal function had only a modest impact on dose requirements.. Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use. A revised guide to the likely allopurinol doses to achieve the target plasma urate concentration is proposed.

Topics: Allopurinol; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Models, Biological; Oxypurinol; Predictive Value of Tests; Uric Acid

To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout.. A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided.. Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures.. Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.

Topics: Adult; Aged; Allopurinol; Cost-Benefit Analysis; Disease Management; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; United States; Uric Acid

To explore the understanding of gout and its management by patients and general practitioners (GP), and to identify barriers to optimal gout care.. Semistructured interviews were conducted with 15 GP and 22 patients in Sydney, Australia. Discussions were focused on medication adherence, experiences with gout, and education and perceptions around interventions for gout. Interviews were audio recorded, transcribed verbatim, and analyzed for themes using an analytical framework.. Adherence to urate-lowering medications was identified as problematic by GP, but less so by patients with gout. However, patients had little appreciation of the risk of acute attacks related to variable adherence. Patients felt stigmatized that their gout diagnosis was predominantly related to perceptions that alcohol and dietary excess were causal. Patients felt they did not have enough education about gout and how to manage it. A manifestation of this was that uric acid concentrations were infrequently measured. GP were concerned that they did not know enough about managing gout and most were not familiar with current guidelines for management. For example and importantly, the strategies for reducing the risk of acute attacks when commencing urate-lowering therapy (ULT) were not well appreciated by GP or patients.. Patients and GP wished to know more about gout and its management. Greater success in establishing and maintaining ULT will require further and better education to substantially benefit patients. Also, given the prevalence, and personal and societal significance of gout, innovative approaches to transforming the management of this eminently treatable disease are needed.

Topics: Allopurinol; Attitude to Health; Australia; Disease Management; Disease Progression; Female; General Practitioners; Gout; Humans; Interviews as Topic; Male; Medication Adherence; Patient Education as Topic; Patient Outcome Assessment; Patient Participation; Risk Assessment; Severity of Illness Index

To investigate the cutaneous tolerance of febuxostat in gouty patients with skin intolerance to allopurinol.. We identified all gouty patients who had sequentially received allopurinol and febuxostat in the rheumatology departments of 4 university hospitals in France and collected data from hospital files using a predefined protocol. Patients who had not visited the prescribing physician during at least 2 months after febuxostat prescription were excluded. The odds ratio (OR) for skin reaction to febuxostat in patients with a cutaneous reaction to allopurinol versus no reaction was calculated. For estimating the 95% confidence interval (95% CI), we used the usual Wald method and a bootstrap method.. In total, 113 gouty patients had sequentially received allopurinol and febuxostat; 12 did not visit the prescribing physician after febuxostat prescription and were excluded. Among 101 patients (86 males, mean age 61±13.9 years), 2/22 (9.1%) with a history of cutaneous reactions to allopurinol showed skin reactions to febuxostat. Two of 79 patients (2.5%) without a skin reaction to allopurinol showed skin intolerance to febuxostat. The ORs were not statistically significant with the usual Wald method (3.85 [95% CI 0.51-29.04]) or bootstrap method (3.86 [95% CI 0.80-18.74]).. The risk of skin reaction with febuxostat seems moderately increased in patients with a history of cutaneous adverse events with allopurinol. This moderate increase does not support the cross-reactivity of the two drugs.

Topics: Aged; Allopurinol; Drug Eruptions; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies

Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known.. To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol.. We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts.. No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28). No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day).. We were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Case-Control Studies; Denmark; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Odds Ratio; Reproducibility of Results; Risk Factors; Treatment Outcome; Uric Acid

Leaves infusion of Pimenta pseudocaryophyllus (Gomes) Landrum is used in Brazilian folk medicine to treat the predisposition to arthritical and gouty affections of the joints, fever and other diseases. A refreshing drink prepared with the specie is also used due to its diuretic, sedative and aphrodisiac actions.. The study was undertaken to investigate the mechanisms of anti-hyperuricemic effect and anti-inflammatory activity of P. pseudocaryophyllus extracts.. Anti-hyperuricemic effect was investigated using xanthine oxidase assay and uricosuric studies with rats in which hyperuricemia was induced by potassium oxonate and uric acid. Anti-inflammatory activity was investigated on MSU crystal-induced paw edema model. Ethyl acetate extracts of the leaves (EAL) and branches (EAB), ethanolic extracts of leaves (EEL) and branches (EEB) and aqueous extracts of leaves (AL) and branches (AB) were evaluated.. The extracts of P. pseudocaryophyllus evaluated showed expressive results regarding the inhibition of xanthine oxidase enzyme in vitro and they were also able to reduce serum uric acid levels in hyperuricemic rats. The investigation of the mechanism of action, it was found that EAL, EAB, EEB, AB (125 and 250 mg/kg) and AL (250 mg/kg) promoted an increase on the urinary excretion of uric acid and EEL, EEB, AB (125 and 250 mg/kg) and EAB (250 mg/kg) were capable to inhibit liver xanthine oxidase. Treatments with EEL (125 and 250 mg/kg) and EEB (250 mg/kg) were able to reduce edema at 48 th h. EAL and EAB (125 and 250 mg/kg) showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema model at all evaluated times.. The specie P. pseudocaryophyllus showed remarkable anti-hyperuricemic effects through uricosuric effects and inhibition of xanthine oxidase and therefore can be considered as a promise in the treatment of diseases related to hyperuricemia. Moreover, ethyl acetate extracts had significant anti-inflammatory activity.

Topics: Animals; Anti-Inflammatory Agents; Gout; Gout Suppressants; Hyperuricemia; Male; Mice; Phytotherapy; Pimenta; Plant Extracts; Plant Leaves; Rats, Wistar; Uric Acid; Xanthine Oxidase

Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout. Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80 mg and 120 mg sequentially, used as first line and second line therapy, was compared with allopurinol 300 mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6 mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied.. National Health System. Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300 mg ranging from €5268-€9737. Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000€/QALY).

Topics: Allopurinol; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Markov Chains; Models, Econometric; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Renal Insufficiency; Spain

The purpose of this study is to describe a novel technique using amniotic membrane suture-fixated onto custom-designed symblepharon rings in a patient with acute toxic epidermal necrolysis (TEN).. A 61-year-old man developed bilateral symblephara and severe ocular surface inflammation from Stevens-Johnson syndrome/TEN secondary to allopurinol. Eight days after admission, he was treated with placement of custom-designed symblepharon rings, designed by one of the authors (A.A.), covered with amniotic membrane. This method was used to allow for efficient placement of the membrane and to minimize operative time and perioperative risks due to his worsening systemic condition.. On postoperative day 49, his visual acuity was 20/20 in the right eye and 20/25 in the left eye. Both eyes were quiet with only small symblephara noted temporally.. The use of amniotic membrane suture-fixated to custom-designed symblepharon rings provides sufficient coverage of the ocular surface, leading to excellent visual and clinical outcomes by reducing inflammation and protecting the ocular surface from the cicatrizing sequelae associated with ocular-involving TEN. This novel technique is less invasive, more time efficient, and likely safe for even the most critically ill patients with significant risk for mortality, thus allowing any treating ophthalmologist to comfortably perform this important sight-saving procedure.

Topics: Acute Disease; Allopurinol; Amnion; Conjunctival Diseases; Eyelid Diseases; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prostheses and Implants; Prosthesis Implantation; Stevens-Johnson Syndrome; Suture Techniques; Visual Acuity; Wound Healing

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthrocentesis; Chondrocalcinosis; Colchicine; Diet Therapy; Gout; Gout Suppressants; Humans; Injections, Intra-Articular; Microscopy, Polarization; Radiography; Synovial Fluid

Topics: Allopurinol; Clinical Trials as Topic; Febuxostat; Gout; Humans; Hyperuricemia; Uric Acid

Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies.. To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD.. A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings.. Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients.. Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur.. No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

Topics: Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Cost-Benefit Analysis; Febuxostat; Female; Gout; Gout Suppressants; Health Care Costs; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; Uric Acid

Many quantitative studies globally have identified suboptimal management of gout.. To explore management of gout from the perspective of general practitioners (GPs), while identifying the barriers and possible strategies for improvement.. This descriptive qualitative study used semistructured interviews with 14 purposely selected GPs from four separate general practices in Townsville. The questions focused on management strategies, practicalities in managing gout, barriers and possible strategies to improve management.. Indomethacin was commonly reported to be used in acute gout with progression to allopurinol after the acute stage had subsided. There were differences with the initial allopurinol dose and follow-up periods. GPs reported lack of patient adherence to allopurinol and lifestyle modifications, mainly due to lack of education. Most suggested the need for allied health input and improved patient education.. Tailor-made plan in terms of education and lifestyle advice could help adherence to gout management.

Topics: Adult; Aftercare; Aged; Allopurinol; Colchicine; Diet Therapy; Disease Management; Female; General Practitioners; Gout; Gout Suppressants; Humans; Indomethacin; Male; Medication Adherence; Middle Aged; Patient Comfort; Patient Education as Topic; Practice Patterns, Physicians'; Qualitative Research; Referral and Consultation; Weight Reduction Programs; Young Adult

To determine the prevalence of anxiety and depression in gout, examine associations between gout characteristics and these comorbidities and determine the role of allopurinol in any such relationships.. As part of a prospective cohort study, a baseline questionnaire was sent to 1805 participants with gout aged≥18 years from UK primary care. Participants had a gout diagnosis or prescriptions for allopurinol or colchicine in their medical records 2 years prior to baseline. Prevalence of anxiety was defined using the Generalised Anxiety Disorder questionnaire and depression using the Patient Health Questionnaire. Logistic regression was used to examine any association between gout characteristics (12-month attack frequency, oligo/polyarticular gout and gout duration) and the presence of anxiety or depression. Crude and adjusted associations were reported as odds ratios (OR) and 95% confidence intervals (CI). Adjusted gout characteristics were stratified by allopurinol use.. One thousand one hundred and eighty-four participants responded to baseline (65.6%). Prevalence of anxiety and depression were 10.0% and 12.6% respectively. There was no association between gout characteristics and anxiety. However, there was an association between attack frequency and depression amongst those gout patients using allopurinol (2.87 [1.2 to 6.6]) and also between oligo/polyarticular gout and depression (2.01 [1.2 to 3.3]), irrespective of allopurinol use (2.09 [1.1 to 4.0]) or not (2.64 [1.0 to 6.8]).. Patients experiencing frequent gout attacks or attacks in multiple joints are likely to experience depressive symptoms, even when using allopurinol. Depression may influence medication adherence and participation in routine reviews, hence impacting adversely on gout management outcomes.

Topics: Aged; Allopurinol; Anxiety; Comorbidity; Depression; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prevalence; Primary Health Care; Prospective Studies; Surveys and Questionnaires; United Kingdom

Uric acid deposition in the pancreas is very rare and neither an endoscopic ultrasound (EUS) nor a contrast-enhanced CT image of this condition has ever been published. We describe a case of asymptomatic pancreatic gout that was detected incidentally on CT. Imaging features mimicked pancreatic neoplasm, warranting further evaluation with EUS-guided fine-needle aspiration. Samples revealed debris encrusted with monosodium urate crystals. Follow-up CT showed complete resolution with urate-lowering therapy. We aim to augment current knowledge on the imaging of pancreatic gout and discuss its management.

Topics: Aged; Allopurinol; Diagnosis, Differential; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Gout; Humans; Incidental Findings; Male; Multimodal Imaging; Pancreatic Diseases; Tomography, X-Ray Computed; Treatment Outcome

Topics: Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Insufficiency, Chronic; Thiazoles; Uric Acid; Xanthine Oxidase

Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout.

Topics: Cholecalciferol; Dietary Supplements; Gout; Health Promotion; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Docking Simulation; Molecular Dynamics Simulation; Nutrition Policy; Protein Conformation; Riboflavin; Xanthine Oxidase

Although international guidelines encourage urate lowering therapy (ULT) for people who have more than two attacks of gout, only 30 % of patients are prescribed it and only 40 % of those adhere to the treatment. The aim was to explore reasons for this through an exploration of patient experience and understanding of ULT treatment for gout.. A qualitative study was conducted throughout the United Kingdom. Narrative and semi-structured video-recorded interviews and thematic analysis were used.. Participants talked about their views and experiences of treatment, and the factors that affected their use of ULT. The analysis revealed five main themes: 1) knowledge and understanding of gout and its treatment; 2) resistance to taking medication; 3) uncertainty about when to start ULT; 4) experiences of using ULT; and 5) desire for information and monitoring.. Patients' understanding and experiences of gout and ULT are complex and it is important for clinicians to be aware of these when working with patients. It is also important for clinicians to know that patients' perceptions and behaviour are not fixed, but can change over time, with changes to their condition, with dialogue and increased understanding. Patients want this interaction with their clinicians, through "a joint effort over a period of time".

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cooperative Behavior; Female; Gout; Gout Suppressants; Health Knowledge, Attitudes, Practice; Humans; Long-Term Care; Male; Medication Adherence; Middle Aged; Motivation; Physician-Patient Relations; Practice Guidelines as Topic; Qualitative Research; Rheumatologists; United Kingdom; Uric Acid

Gout is a chronic disease characterized by the deposition of urate crystals in the joints and throughout the body, caused by an excess burden of serum uric acid (sUA). The study estimates pharmacy and medical cost budgetary impacts of wider adoption by US payers of febuxostat, a urate-lowering therapy (ULT) for the treatment of gout.. A US payer-perspective budget impact model followed ULT patients from a 1,000,000-member plan over 3 years. The current market share scenario, febuxostat (6%) and ULT allopurinol (94%), was compared with an 18% febuxostat market share. Data were implemented from randomized controlled trials, census and epidemiologic studies, and real-world database analyses. An innovation was the inclusion of gout-related chronic kidney disease costs. Cost results were estimated as annual and cumulative incremental costs, expressed as total costs, cost per member per month, and cost per treated member per month. Clinical results were also estimated.. Increasing the febuxostat market share resulted in a 6.3% increase in patients achieving the sUA target level of <6.0 mg/dL and a 1.4% reduction in gout flares during the 3-year period. Total cost increased 1.4%, with a 49.9% increase in ULT costs, a 1.4% reduction in flare costs, a 1.2% reduction in chronic kidney disease costs, and a 2.8% reduction in gout care costs. The cumulative incremental costs were $1,307,425 in the first year, $1,939,016 through the second year, and $2,092,744 through the third year. By the third year, savings in medical costs offset most of the increase in treatment costs. Impacts on cumulative cost per member per month and cumulative cost per treated member per month followed the same pattern, with the highest impact in the first year and cumulative impacts declining during the 3-year period. The cumulative cost per member per month impact was estimated as $0.109, $0.081, and $0.058 and the cumulative cost per treated member per month impact was estimated as $12.416, $9.207, and $6.625 in the first year, through the second year, and through the third year, respectively.. Expanding the febuxostat market share would result in improved clinical outcomes, but with an overall increase in costs over 3 years due to higher costs of treatment. By the third year, savings in medical costs, primarily in chronic kidney disease costs, would offset most of the increase in treatment costs. Expanded use of febuxostat in the treatment of all gout patients, independent of renal impairment status, should be considered based on improved clinical outcomes and longer-term medical cost savings associated with these improved outcomes.

Topics: Adult; Aged; Allopurinol; Budgets; Chronic Disease; Febuxostat; Female; Gout; Gout Suppressants; Health Care Costs; Humans; Male; Managed Care Programs; Middle Aged; Pharmaceutical Services; Renal Insufficiency, Chronic; United States; Uric Acid; Young Adult

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Insufficiency, Chronic; Thiazoles; Uric Acid

Topics: Allopurinol; Creatinine; Gout; Gout Suppressants; Humans; Uric Acid

Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid.. To assess the safety and efficacy of benzbromarone in a real-life setting.. All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified. Prescribers were sent a questionnaire for each individual. Information on demographics, efficacy of previous urate-lowering drugs and reasons for discontinuation were collected. Specific information about the dose, effect on serum urate, adverse effects and liver function tests after commencing benzbromarone was recorded.. Completed questionnaires were returned for 123 of 164 (75%) patients. Mean (SD) serum urate prior to benzbromarone was 0.57 (0.12) mmol/L, and estimated glomerular filtration rate was 50.3 (22.8) mL/min/1.73 m(2) . The median dose of benzbromarone was 100 mg/day (25-200 mg/day). Six months after commencing benzbromarone, mean (SD) serum urate was 0.35 (0.12) mmol/L. Benzbromarone-related adverse events included rash (n = 4), diarrhoea (n = 9), nausea (n = 6) and urate stones (n = 3). Liver function test abnormalities were uncommon and tended to be mild. There were 14 patient deaths; none was considered related to benzbromarone. Allopurinol had been prescribed prior to benzbromarone in 117 of 123 patients; median maximum allopurinol dose was 200 mg/day (range 25-600 mg/day), and 19% patients received allopurinol >300 mg/day.. Benzbromarone provides useful urate-lowering efficacy and does not appear unsafe in patients with gout. Urate-lowering therapy prescribing requires further optimisation.

Topics: Aged; Allopurinol; Benzbromarone; Comorbidity; Exanthema; Female; Gout; Gout Suppressants; Humans; Kidney Function Tests; Liver Function Tests; Male; Middle Aged; New Zealand; Retrospective Studies; Uric Acid; Uricosuric Agents

BACKGROUND Gout is characterized by deposition of uric acid crystals (monosodium urate) in tissues and fluids. This can cause acute inflammatory arthritis. The 2015 ACR/EULAR criteria for the diagnosis of gout include dual energy computed tomography (DECT)-demonstrated monosodium urate crystals as a new criterion. DECT is a spectral decomposition that permits recognition of different types of tissues based on their characteristic energy-dependent photon attenuation. A positive scan is defined as the presence of urate at articular or periarticular sites. CASE REPORT We describe a 51-year-old woman known to have anorexia nervosa. During our clinical examination, we detected plenty of tophi on both hands, but no swollen joints. The diagnosis of gout was made by visualizing crystals in a biopsy from a tophus. The first line of treatment was allopurinol, the second line was rasburicase, and the current treatment is febuxostat 80 mg/day, allopurinol 300 mg twice a day, and colchicine 0.5 mg twice a day. The patient has unchanged arthralgia and the size and number of tophi remain the same as before treatment in spite of active treatment for 3 years. Previously the patient had problems with adherence, but now she claims that she follows the proposed treatment. The last plasma urate (P-urate) was 0.57 mmol/L. Following two years of treatment, DECT of hands visualized monosodium urate crystal deposits in the tophi, as seen on the clinical photos, but also crystals in relation to the tendons and soft tissue.  CONCLUSIONS DECT is an imaging modality useful to assess urate crystal deposits at diagnosis of gout and could be considered during treatment evaluation. Lack of adherence to treatment should be considered when P-urate values vary significantly and when DECT scans over years persistently visualize monosodium urate crystals.

Topics: Absorptiometry, Photon; Allopurinol; Anorexia Nervosa; Biomarkers; Biopsy; Colchicine; Drug Therapy, Combination; Febuxostat; Female; Gout; Gout Suppressants; Humans; Middle Aged; Patient Compliance; Predictive Value of Tests; Sensitivity and Specificity; Urate Oxidase; Uric Acid

Gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals, is commonly seen in primary care and specialist clinics. In recent years, there has been a resurgence of interest in gout due to advances in therapies and the understanding of pathophysiology, with new guidelines being published by international bodies. However, there is still a gap between the goals of treatment and actual day-to-day practice. Barriers that result in poorly controlled gout include patient factors such as lack of understanding of the disease, stigma and nonadherence to treatment, as well as physician factors such as knowledge gaps, inadequate use of allopurinol and lack of ownership of the disease. The medical profession needs to do more to bridge the gap through physician and patient education, identification of treatment targets with appropriate use of drugs, and dissemination of guidelines.

Topics: Allopurinol; Arthritis; Comorbidity; Gout; Humans; Hyperuricemia; Inflammation; Medication Adherence; Patient Education as Topic; Primary Health Care; Professional-Patient Relations; Rheumatology; Singapore; Uric Acid

Topics: Allopurinol; Drug Costs; Febuxostat; Fingers; Gout; Gout Suppressants; Health Equity; Humans; Male; Middle Aged; Symptom Flare Up

Patients' perceptions of their illness are dynamic and can directly influence aspects of management. Our aim was to examine the illness perceptions of gout patients in UK primary care and associations with allopurinol use.. A health questionnaire was sent to 1805 people with gout aged ≥18 years identified by a gout diagnosis or prescriptions for allopurinol or colchicine in their primary care medical records in the preceding 2 years. The questionnaire included selected items from the revised illness perception questionnaire (IPQ-R). Associations between illness perceptions and use of allopurinol were calculated using multinomial logistic regression adjusted for age, gender, deprivation status, body mass index, alcohol consumption, comorbidities and gout characteristics.. One thousand one hundred eighty-four participants responded to the baseline questionnaire (65.6 %). Approximately half of responders perceived that they were able to control (51.2 %) or affect their gout through their own actions (44.8 %). Three quarters perceived treatments to be effective (76.4 %) and agreed that gout is a serious condition (76.4 %). Patients who agreed that they could control their gout (Relative Risk Ratio, 95 % confidence interval 1.66 (1.12 to 2.45)) and that treatments were effective (2.24 (1.32 to 3.81)) were more likely to currently be using allopurinol than not using allopurinol. However, this significance was attenuated after adjustment for self-reported gout characteristics (1.39 (0.89 to 2.17) & 1.78 (0.96 to 3.29) respectively).. Patients who perceive that they can control their gout and that treatments are effective are more likely to be using allopurinol, this suggests that better information is needed for the patient from GPs and rheumatologist to reassure and support their use of ULT.

Topics: Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies

Although gout is potentially curable, the management of this disease is often suboptimal. In this study, we investigated the treatment of gout in Turkey and also compared the management approaches to gout in different clinical specialties. Three hundred and nineteen consecutive patients (mean age 58.60 ± 12.8 years; 44 females, 275 males) were included in this multicenter study. A standardized form was generated to collect data about the patient's first admission to health care, the specialty of the doctor first diagnosed the gout, the treatment options for gout including attack management, patient referral, chronic treatment including medical treatment, and life style modifications. Forty patients were referred to another center without any treatment (12.8 %), and referral rate is most common among the primary care physicians (28.8 %). Colchicine was more commonly used for attack prophylaxis than allopurinol. Ninety-two patients had never been treated with allopurinol (28.8 %). Allopurinol prescription was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. Recommendation of diet and life style modifications was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. The rates of life style modification recommendation and long-term allopurinol prescription were 83.7 and 77.6 %, respectively, among the rheumatologists. Both acute and chronic management of gout is suboptimal in Turkey especially among the primary care physicians and orthopedists. Moreover, chronic treatment is even suboptimal among rheumatologists.

Topics: Adult; Aged; Allopurinol; Colchicine; Female; Gout; Gout Suppressants; Humans; Internal Medicine; Life Style; Male; Middle Aged; Orthopedics; Patient Admission; Physical Therapy Specialty; Primary Health Care; Rheumatology; Surveys and Questionnaires; Turkey; Uric Acid

The British Journal of Hospital Medicine is 50 years old. This article takes a look back at articles published during the year of its inception from the British Medical Journal, the Lancet and the Journal of the American Medical Association.

Topics: Abortion, Induced; Acetaminophen; Adrenocortical Adenoma; Allopurinol; Analgesics; Antineoplastic Agents; Attitude of Health Personnel; Attitude to Health; Bird Fancier's Lung; Celiac Disease; Chemical and Drug Induced Liver Injury; Dermatitis Herpetiformis; Drug Discovery; Gout; Gout Suppressants; Graft Rejection; Granulomatous Disease, Chronic; History, 20th Century; Humans; Medicare; Periodicals as Topic; Publishing; United Kingdom; United States

Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further.. To investigate whether XOIs and colchicine are associated with decreased risk of MI.. This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings.. The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)).. Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect.

Topics: Aged; Allopurinol; Case-Control Studies; Colchicine; Female; Gout; Gout Suppressants; Humans; Hypertension; Logistic Models; Male; Middle Aged; Myocardial Infarction; Protective Factors

Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population.. We conducted an incident user cohort study with propensity score matching using a UK general population database. The study population included individuals aged ≥40 years who had a record of hyperuricaemia (serum urate level >357 μmol/L for women and >416 μmol/L for men) between January 2000 and May 2010. To closely account for potential confounders of allopurinol use and risk of death, we constructed propensity score matched cohorts of allopurinol initiators and comparators (non-initiators) within 6-month cohort accrual blocks.. Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92).. In this general population study, allopurinol initiation was associated with a modestly reduced risk of death in patients with hyperuricaemia and patients with gout. The overall benefit of allopurinol on survival may outweigh the impact of rare serious adverse effects.

Topics: Aged; Allopurinol; Cohort Studies; Databases, Factual; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Incidence; Male; Risk Factors; Survival Rate; Treatment Outcome; United Kingdom

We report three Caucasian patients affected by gout and type 2 diabetes, who were treated with the recombinant nonglycosylated human interleukin-1 receptor antagonist anakinra (100 mg/day subcutaneously) after an unsatisfactory or incomplete response to urate-lowering therapy, colchicine, nonsteroidal anti-inflammatory drugs, and prednisone. The remarkable clinical improvement in joint symptoms within 24 h and in glycemic control during a 6-month period gives anakinra a potential therapeutic role in the management of gout and type 2 diabetes. When anakinra was discontinued, a gout attack occurred within 3-25 days in all three patients. The contribution of anakinra in the treatment of such syndromes is encouraging, but requires further studies to establish its long-term efficacy.

Topics: Aged; Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Blood Glucose; Carbamates; Colchicine; Diabetes Mellitus, Type 2; Febuxostat; Glycated Hemoglobin; Gout; Gout Suppressants; Humans; Hyperuricemia; Hypoglycemic Agents; Insulin; Interleukin 1 Receptor Antagonist Protein; Metformin; Middle Aged; Piperidines; Treatment Outcome; Uric Acid

Allopurinol-induced severe cutaneous adverse reactions (SCARs) are relatively rare but cause high rates of morbidity and mortality. Studies have shown that the HLA-B5801 allele and renal impairment are strongly associated with SCARs. Recent American College of Rheumatology guidelines recommend that, prior to treatment with allopurinol, the HLA-B5801 genotype of gout patients at high risk for SCARs, including Korean patients with chronic renal insufficiency, should be determined. However, whether such genotyping is cost-effective is unknown. This study evaluated the cost-effectiveness of HLA-B5801 genotyping for the treatment of gout in patients with chronic renal insufficiency in Korea.. A decision analytical model over a time period of 12 months was employed to compare the cost and outcomes of treatment informed by HLA-B5801 genotyping with that of a conventional treatment strategy using a hypothetical cohort of gout patients with chronic renal insufficiency. Direct medical costs were obtained from real patients with SCARs from 2 tertiary hospitals. Outcomes were measured as a total expected cost and an incremental cost-effectiveness ratio.. In the base model, the total expected cost and probability of continuation of gout treatment without SCARs for the conventional and HLA-B5801 screening strategies were $1,193 and 97.8% and $1,055 and 100%, respectively. The results were robust according to sensitivity analyses.. Our model suggests that gout treatment informed by HLA-B5801 genotyping is less costly and more effective than treatment without genotyping, and HLA-B5801 genotyping could considerably reduce the occurrence of allopurinol-induced SCARs and related deaths.

Topics: Allopurinol; Cost-Benefit Analysis; Decision Trees; Drug Eruptions; Genotype; Genotyping Techniques; Gout; Gout Suppressants; HLA-B Antigens; Humans; Renal Insufficiency, Chronic; Republic of Korea

The objective of this study was to explore the health literacy of patients dealing with gout and to understand perceptions that might account for non-adherence to urate-lowering therapy (ULT). Semi-structured interviews involving patients with gout were conducted. The transcripts of the interviews were scored by two readers and a coding system to categorize the data was developed. Fifteen patients (14 men, mean age 63 years, mean disease duration 11 years) were interviewed; ten patients were recruited from secondary care and five from primary care. Six patients had gout tophi and 12 patients used ULT. Less than half of the patients were sufficiently aware of the pathophysiological processes that cause gout. Twelve patients indicated that treatment of gout only encompasses treatment of the acute attack. Patients were unaware of long-term treatment goals. Six patients admitted medication non-adherence at some point in time. Several reasons for non-adherence, such as healthcare professionals providing conflicting messages about medication, can be considered preventable. Half of the patients expressed that they, especially at the time of diagnosis, wanted to know more about the cause of gout, treatment goals and long-term consequences. In conclusion, the health literacy of patients dealing with gout was low in our study, especially with regard to medication. Yet, patients often recognized these knowledge gaps. Our data suggest that improving knowledge and addressing common misperceptions in training programmes, may ultimately contribute to adherence to ULT and an optimized outcome in patients with gout. This hypothesis needs to be confirmed in future research.

Topics: Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Health Literacy; Humans; Interviews as Topic; Male; Medication Adherence; Middle Aged; Perception; Professional-Patient Relations; Qualitative Research; Uric Acid

To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout.. We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl.. We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation.. Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.

Topics: Aged; Allopurinol; Databases, Factual; Delivery of Health Care, Integrated; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Retrospective Studies; Treatment Outcome; Uric Acid

To quantify the risk of non-fatal acute myocardial infarction (AMI) among users of allopurinol.. We carried out a population-based case-control study over the period 2001-2007 in patients aged 40-90 years. Patients who had prescriptions of allopurinol or an episode of AMI before the start date of follow-up were excluded from the main analysis. Allopurinol initiators were classified as current users if their last prescription ended in the 30-day window before the recorded date of AMI for cases and a random date for controls. The association between use of allopurinol and non-fatal AMI was measured through an OR and adjusted for confounding factors by an unconditional logistic regression.. We identified 3171 cases of non-fatal AMI and 18 525 controls. Cases had a lower prevalence of current use of allopurinol (0.82%) than controls (1.03%), yielding to an OR of 0.52 (95% CI 0.33 to 0.83). The decreased risk was driven by men (OR in men=0.44; 95% CI 0.25 to 0.76; OR in women=0.90; 0.36 to 2.23). No difference by age was observed. The effect was only observed at higher doses (300 mg or greater OR=0.30; 0.13 to 0.72; <300 mg OR=0.67; 0.37 to 1.23) and with prolonged treatments (<31 days, OR=1.12 (0.55 to 2.29); 31-180 days, OR=0.61; 0.29 to 1.29; >180 days OR=0.21; 0.08 to 0.53; p for trend=0.001). Among those with a previous AMI, allopurinol use also showed a significant reduced risk of recurrence (OR=0.16; 0.04 to 0.76).. The present study supports the hypothesis that allopurinol is associated with a reduced risk of non-fatal AMI, which seems to be dose-dependent and duration-dependent.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Female; Free Radical Scavengers; Gout; Humans; Hyperuricemia; Male; Middle Aged; Myocardial Infarction; Risk Factors; Uric Acid

Gout is a chronic inflammatory condition associated with poor urate metabolism. Xanthine oxidase inhibitors such as allopurinol and febuxostat are recommended to reduce uric acid levels and to prevent gout attacks in adult patients. Under budget-driven constraints, health care payers are faced with the broader challenge of assessing the economic value of these agents for formulary placement. However, the economic value of allopurinol versus febuxostat has not be assessed in patients with gout over a 5-year time period in the United States.. To evaluate the cost-effectiveness of allopurinol versus febuxostat in adult patients with gout over a 5-year time period from a U.S. health care payer's perspective.. A Markov model was developed to compare the total direct costs and success of serum uric acid (sUA) level reduction associated with allopurinol and febuxostat. Treatment success was defined as patient achievement of a sUA level less than  6 mg/dL (0.36 mmol/L) at 6 months. Event probabilities were based on published phase III randomized clinical trials and included long-term sequelae from open-label extension studies. A hypothetical cohort of 1,000 adult gout patients with sUA levels of ≥ 8 mg/dL (0.48 mmol/L) who had received either allopurinol 300 mg or febuxostat 80 mg at model entry transitioned among the 4 health states defined by treatment success, treatment failure and switch, treatment dropout, and death. The length of each Markov cycle was 6 months. Costs were gathered from the RED BOOK, Medicare fee schedules, Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, and for a limited number of inputs, expert consultation. Direct costs included treatment drug costs, costs for prophylaxis drugs, diagnostic laboratory tests, and the treatment and management of acute gout flare. Resource utilization was based on clinical evidence and expert consultation. All costs were inflated to 2014 U.S. dollars and were discounted at 3% in the base case. One-way sensitivity analysis and probabilistic sensitivity analyses (PSAs) were performed to assess the robustness of the results.. The total per patient cost incurred over 5 years was $50,295 for febuxostat and $48,413 for allopurinol, with an incremental total cost of $1,882. The expected percentage of treatment success during the 5-year period was 72 for febuxostat and 42 for allopurinol, resulting in an incremental percentage of treatment success of 30. The estimated incremental cost-effectiveness ratio for febuxostat compared with allopurinol was $6,322 per treatment success over a 5-year time period. The one-way sensitivity analysis indicated that the results were sensitive to probability of treatment success for allopurinol, probability of treatment dropouts for both allopurinol and febuxostat, and the probability of failure and switch to allopurinol. PSAs demonstrated that at a willingness-to-pay threshold of $50,000 per treatment success, febuxostat was cost-effective compared with allopurinol.. Febuxostat was found to be a cost-effective option compared with allopurinol based on a U.S. payer perspective.

Topics: Allopurinol; Chronic Disease; Cost-Benefit Analysis; Febuxostat; Gout; Gout Suppressants; Humans; Markov Chains; Thiazoles; Uric Acid

An emphasis on renal function in deciding maintenance doses of allopurinol to prevent allopurinol hypersensitivity has resulted in ineffective prevention of attacks of gout. New therapeutic guidelines for gout have shifted the focus back to titrating maintenance doses to reach a serum uric acid (SUA) concentration target of ≤ 0.36 mmol/L.. To examine trends in the prescribing of allopurinol in a teaching hospital and their concordance with the new guidelines for gout management, and to explore prescribers' approaches and attitudes to the use of allopurinol.. An audit was conducted of all inpatients prescribed allopurinol at a teaching hospital between January 2008 and December 2012. Allopurinol dose, SUA, serum creatinine concentrations and estimated glomerular filtration rates were extracted from the hospital databases. Doctors from medical units who regularly prescribed allopurinol were interviewed.. The allopurinol dose prescribed in gout patients most commonly was a continuation of the pre-admission dosage. Dosage change during admission was rarely observed. Dosages reflected a consideration of renal function. SUA concentrations were measured in only 21% (n = 269) of gout patients. Prescriber interviews (n = 12) reflected adequate knowledge regarding allopurinol use, but most maintained that the primary care setting was more suitable for the management of dose titration in gout.. SUA concentrations were not routinely measured in the majority of admitted gout patients taking allopurinol. Without SUA measurements and allopurinol dose titration, patients with SUA > 0.36 mmol/L are at increased risk for acute attacks of gout in hospital.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Comprehension; Female; Gout; Gout Suppressants; Hospitals, Teaching; Humans; Male; Medical Audit; Middle Aged; Young Adult

Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.. We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.. There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.. Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.

Topics: Adult; Cohort Studies; Female; Gout; Gout Suppressants; Heart Diseases; Humans; Hyperuricemia; Male; Middle Aged; Risk Factors; Xanthine Oxidase

Allopurinol is used as long-term therapy to reduce the occurrence of gout flares. This study estimated the impact of patient adherence to allopurinol on hyperuricaemia (serum uric acid levels, sUA > 6 mg/dl) and the identification of non-adherence predictors.. The Italian Health Search-CSD Longitudinal Patient Database was accessed to identify outpatients aged ≥ 18 years with gout and prescribed with allopurinol during the years 2002-2011. Patients with a proportion of days covered ≥ 80% were considered adherent to allopurinol. Data on sUA levels over the first year of therapy were categorised in three time-windows (30-89; 90-149; 150-365 days). Logistic regressions were used to estimate the association between adherence and hyperuricaemia, as well as non-adherence predictors.. A total of 3727 patients were included. In the interval 0-29 days, the proportion of patients adherent to allopurinol was 45.9%, while up to 89, 149 and 365 days the percentages were 16.7%, 10.0% and 3.2%, respectively. The proportions of hyperuricaemic patients for each time-window were 43.1%, 42.4%, 32.6% and 59.0%, 64.0%, 66.4% among adherent and non-adherent patients, respectively. In the multivariable analysis, adherence was associated with a significant lower risk of hyperuricaemia. The adjusted ORs were 0.49 (95% CI: 0.33-0.73), 0.40 (95% CI: 0.24-0.67) and 0.23 (95% CI: 0.15-0.34) for the first, second and third time-window, respectively. Patients with hypertension (adjusted OR = 0.64, 95% CI: 0.42-0.99) and history of gout flares (adjusted OR = 0.55, 95% CI: 0.32-0.95) were significantly adherent to allopurinol.. Adherence monitoring in patients with gout is pivotal to ensure the effectiveness of therapy. To gain a better patient adherence, the communication between physicians and patients should be improved.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Databases, Factual; Dose-Response Relationship, Drug; Female; Follow-Up Studies; General Practice; Gout; Gout Suppressants; Humans; Incidence; Italy; Male; Middle Aged; Patient Compliance; Retrospective Studies; Time Factors; Uric Acid; Young Adult

To increase the knowledge of epidemiology and treatment of gout in a 'real-life' setting, we conducted a large observational analysis (CACTUS) in two European countries, namely France and Greece.. This was a multicenter, cross-sectional, observational analysis, conducted in France and Greece. The analysis was conducted in a field-practice scenario, with both general practitioners and rheumatologists recruiting patients for inclusion. Treatment methods and drug prescriptions were left to the sole initiative of the participating physicians. A number of epidemiological and clinical characteristics were recorded in a single inclusion visit. Compliance to maintenance treatment was also monitored after the inclusion visit by monthly interview.. In total 3079 patients were included. Hypertension was the most common co-morbidity (68%), followed by hypercholesterolemia (59%) and obesity (48%). Mean serum Uric Acid (sUA) concentration was 8.7 mg/dl. Almost all patients received life-style or dietary recommendations. At inclusion, 81.5% of patients were on a urate-lowering treatment. Most of these patients had been treated with allopurinol; this treat-ment had been interrupted for lack of reduction of sUA levels below 6 mg/dl (47%), lack of symptom relief (34%) or poor compliance (23%). At the inclusion visit, 98% of the patients were prescribed an urate-lowering treatment: 87% received febuxostat and 12% allopurinol alone. Satisfactory or very satisfactory compliance to febuxostat was recorded in 92% of the patients, versus 82% in patients on allopurinol.. CACTUS provides an overview of characteristics of gouty patients and gout management. Education of patients by healthcare providers seem to be a pre-requisite to optimize the management of gout, a condition which remains poorly man-aged.

Topics: Adult; Allopurinol; Cohort Studies; Comorbidity; Cross-Sectional Studies; Europe; Febuxostat; Female; France; Gout; Gout Suppressants; Greece; Humans; Male; Middle Aged; Obesity; Patient Compliance; Thiazoles; Uric Acid

In the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donor's risk of gout as serum uric acid concentration increases in donors after nephrectomy.. Retrospective matched cohort study using large health care databases.. We studied living kidney donors who donated in 1992 to 2010 in Ontario, Canada. Matched nondonors were selected from the healthiest segment of the general population. 1,988 donors and 19,880 matched nondonors were followed up for a median of 8.4 (maximum, 20.8) years.. Living kidney donor nephrectomy.. The primary outcome was time to a diagnosis of gout. The secondary outcome in a subpopulation was receipt of medications typically used to treat gout (allopurinol or colchicine).. We assessed the primary outcome with health care diagnostic codes.. Donors compared with nondonors were more likely to be given a diagnosis of gout (3.4% vs 2.0%; 3.5 vs 2.1 events/1,000 person-years; HR, 1.6; 95% CI, 1.2-2.1; P<0.001). Similarly, donors compared with nondonors were more likely to receive a prescription for allopurinol or colchicine (3.8% vs 1.3%; OR, 3.2; 95% CI, 1.5-6.7; P=0.002). Results were consistent in multiple additional analyses.. The primary outcome was assessed using diagnostic codes in health care databases. Laboratory values for serum uric acid and creatinine in follow-up were not available in our data sources.. The findings suggest that donating a kidney modestly increases an individual's absolute long-term incidence of gout. This unique observation should be corroborated in future studies.

Topics: Adult; Allopurinol; Case-Control Studies; Cohort Studies; Colchicine; Female; Gout; Gout Suppressants; Humans; Kidney Transplantation; Living Donors; Male; Middle Aged; Nephrectomy; Ontario; Retrospective Studies; Risk Factors

Gout is a chronic metabolic disease caused by disturbance of purine metabolism that leads to hyperuricemia. Hyperuricemia prevalence after renal transplant is reported as 19% to 84% in different studies. Tophaceous gout in renal transplant recipients is a consequence of increased hyperuricemia. Although tophus formation in skin and soft tissues is an indicator of chronic gout (also referred to as tophaceous gout), tophi may be the first sign of gout. In this study, we report a case of a 62-year-old male renal transplant recipient who had tophi as the first clinical sign of gout. After confirming gout diagnosis, cyclosporine was changed to sirolimus, and allopurinol was added to therapy to decrease uric acid levels. In conclusion, hyperuricemia is a common complication in renal transplant recipients. Presentation might be atypical, and diagnosis can be challenging.

Topics: Allopurinol; Cyclosporine; Drug Substitution; Gout; Gout Suppressants; Humans; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Risk Factors; Sirolimus; Skin; Treatment Outcome

To assess the comparative effectiveness of febuxostat and allopurinol in reducing serum urate (sUA) levels in a real-world U.S. managed care setting.. This retrospective study utilized 2009 to 2012 medical and pharmacy claims and laboratory data from a large U.S. commercial and Medicare Advantage health plan. Study patients had at least one medical claim with a diagnosis of gout, at least one filled prescription for febuxostat or allopurinol and at least one sUA measurement post-index prescription. Reduction in sUA was examined using propensity score-matched cohorts, matched on patient demographics (gender, age), baseline sUA, comorbidities, geographic region and insurance type.. The study sample included 2,015 patients taking febuxostat and 14,025 taking allopurinol. At baseline, febuxostat users had a higher Quan-Charlson comorbidity score (0.78 vs. 0.53; P <0.001), but similar age and gender distribution. Mean (standard deviation (SD)) sUA level following propensity score matching among treatment-naïve febuxostat vs. allopurinol users (n = 873 each) were: pre-index sUA, 8.86 (SD, 1.79) vs. 8.72 (SD, 1.63; P = 0.20); and post-index sUA, 6.53 (SD, 2.01) vs. 6.71 (SD, 1.70; P = 0.04), respectively. A higher proportion of febuxostat users attained sUA goals of <6.0 mg/dl (56.9% vs. 44.8%; P <0.001) and <5.0 mg/dl (35.5% vs. 19.2%; P <0.001), respectively. Time to achieve sUA goals of <6.0 mg/dl (346 vs. 397 days; P <0.001) and <5.0 mg/dl was shorter in febuxostat vs. allopurinol users (431 vs. 478 days; P <0.001), respectively. Similar observations were made for overall propensity score-matched cohorts that included both treatment-naïve and current users (n = 1,932 each).. Febuxostat was more effective than allopurinol at the currently used doses (40 mg/day for febuxostat in 83% users and 300 mg/day or lower for allopurinol in 97% users) in lowering sUA in gout patients as demonstrated by post-index mean sUA level, the likelihood of and the time to achieving sUA goals.

Topics: Aged; Allopurinol; Cohort Studies; Cost-Benefit Analysis; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Managed Care Programs; Medicare; Reference Values; Retrospective Studies; Severity of Illness Index; Treatment Outcome; United States; Uric Acid

A human leukocyte antigen haplotype comprising six single-nucleotide polymorphisms (SNPs) confers risk for allopurinol hypersensitivity syndrome in Caucasians. The objective of the current study was to test for association of this haplotype with other, less severe adverse effects (AEs) of allopurinol therapy in a large New Zealand gout cohort. A total of 626 Caucasian and 766 Polynesian patients were genotyped for six SNPs (rs2844665, rs9263715, rs3130931, rs3130501, rs3094188, rs9469003) using TaqMan SNP assays. The CACGAC haplotype occurred at a frequency of 0.018 in Caucasians and 0.009 in Polynesians. The CACGAC haplotype occurred at a significantly higher frequency in Caucasian patients who experienced allopurinol-related AEs (13.3 vs. 1.7%, P=8.9e-06, odds ratio=8.9, 95% confidence interval 2.8-27.9), but it was not associated with overall allopurinol toxicity in Polynesians (P>0.05). Our study is the first to demonstrate the potential utility of this six-SNP haplotype as a predictor of milder allopurinol AEs.

Topics: Allopurinol; Genetic Loci; Genetic Predisposition to Disease; Gout; Haplotypes; HLA Antigens; Humans; Polynesia; Risk Factors; White People

Topics: Allopurinol; Arthritis; Cartoons as Topic; Gout; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Inflammation; Uric Acid

Comparative effectiveness research could help inform the choice of agent for urate-lowering therapy, the central component of successful gout management. However, if such studies reflect current clinical practice, are they comparing poor management with inadequate management?

Topics: Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male

To estimate the time course of changes in the clinical manifestations of gout and their risk factors during a long-term follow-up.. A total of 160 male patients with gout were examined and followed up for a mean of 6.9 ± 2.0 years. Their clinical assessment included determination of the type of arthritis over time, the frequency of arthritis attacks during one year prior to the examination, the presence and number of subcutaneous tophi, inflamed joints, comorbid or co-occurring diseases (CD), allopurinol adherence, dietary compliance, frequency of taking non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, and alcohol. The serum levels of uric acid (UA), glucose, total cholesterol, and glomerular filtration rate were estimated.. The number of patients taking allopurinol increased from 19% to 64% (p < 0.0001), its average daily dose was 167.6 ± 94.6 mg. The serum level of UA decreased; 16% of the patients achieved its target level. The number of patients with chronic arthritis was not significantly changed. Their serum level of UA was unchanged; the detection rate of subcutaneous tophi and CD rose. During one year, arthritis attacks were absent in 13% of the patients; 90% of them took allopurinol. In these patients, serum UA levels and body mass index significantly declined and the rate of CD was unchanged. None of 18 patients who had their diet and no allopurinol achieved the target level of UA.. Among the gouty patients, 36% refrain from the use of allopurinol, only 23% out of them require that its dose be adjusted to achieve the target level of UA. Dietary compliance is insufficient to reach the target level of UA. Chronic arthritis is associated with the increased incidence of CD.. Цель исследования. Оценка динамики клинических проявлений подагры и факторов, влияющих на них, при длительном наблюдении. Материалы и методы. Обследовали 160 больных подагрой мужчин, средний период наблюдения за которыми составил 6,9±2 года. Клиническая оценка включала определение в динамике варианта артрита, частоты приступов артрита за предшествующий осмотру год, наличия и количества подкожных тофусов, воспаленных суставов, коморбидных, или сочетанных, заболеваний (СЗ), соблюдение схемы приема аллопуринола, диеты, частоты приема нестероидных противовоспалительных препаратов, диуретиков, алкоголя. Определяли в сыворотке крови уровни мочевой кислоты (МК), глюкозы, общего холестерина, рассчитывали скорость клубочковой фильтрации. Результаты. Число больных, принимавших аллопуринол, увеличилось с 19 до 64% (р<0,0001), средняя суточная доза составила 167,6±94,6 мг. Уровень МК в сыворотке крови снизился, целевой уровень достигнут у 16% больных. Число больных хроническим артритом достоверно не изменилось. Уровень МК в сыворотке крови у них не изменился, увеличилась частота выявления подкожных тофусов, СЗ. Приступы артрита в течение года отсутствовали у 13% больных, 90% из них принимали аллопуринол. У этих больных достоверно снизились уровень МК в сыворотке крови и индекс массы тела, частота СЗ не изменилась. Ни у одного из 18 больных, соблюдавших диету и не принимавших аллопуринол, целевой уровень МК не достигнут. Заключение. Среди больных подагрой 36% воздерживаются от приема аллопуринола, только 23% из них подбирают дозу препарата до достижения целевого уровня МК. Соблюдения диеты недостаточно для достижения целевого уровня МК. Наличие хронического артрита ассоциируется с увеличением частоты развития СЗ.

Topics: Adult; Aged; Allopurinol; Arthritis, Gouty; Follow-Up Studies; Gout; Gout Suppressants; Humans; Middle Aged; Remission Induction; Retrospective Studies; Time Factors; Uric Acid

Topics: Allopurinol; Asymptomatic Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Hypersensitivity Syndrome; Gout; Humans; Hypertension; Hyperuricemia; Renal Insufficiency; Risk Factors

To examine the association between allopurinol use and all-cause mortality for patients with incident gout.. We compared all-cause mortality in incident gout patients who received allopurinol for at least 6 months within the exposure window (1 year or 3 years) with those who did not, using the UK Clinical Practice Research Data-link. Landmark analysis was used to account for immortal time bias and propensity score matching was used to control for potential effects of known confounders.. Of 23 332 incident gout patients identified, the propensity score-matched cohorts contained 1016 patients exposed to allopurinol on the date 1 year from diagnosis (landmark date) and 1016 allopurinol non-users. Over a median follow-up period of 10 years after the landmark date, there were 437 allopurinol users and 443 allopurinol non-users who died during follow-up. Allopurinol users and non-users had similar risk for all-cause mortality (hazard ratio 0.99; 95% CI 0.87, 1.12). In the 3-year landmark analysis, 3519 allopurinol users (1280 died) were compared with 3519 non-users (1265 died). The hazard ratio for all-cause mortality was 1.01 (95% CI 0.92, 1.09).. This propensity score-matched landmark analysis in a population of incident gout patients in the UK primary care setting found a neutral effect on the risk of all-cause mortality. Our study provides reassurance about the prescription of allopurinol for gout patients early in their disease course to prevent untoward consequences of chronic uncontrolled hyperuricaemia. However, whether higher than the commonly used dose of allopurinol could influence mortality remains to be determined.

Topics: Aged; Allopurinol; Databases, Factual; Drug Administration Schedule; Female; Gout; Gout Suppressants; Humans; Incidence; Male; Middle Aged; Propensity Score; United Kingdom

Gout is a common clinical problem encountered by both general and specialist clinicians. The key principles in gout management include establishing a definitive diagnosis, the swift treatment of acute attacks, and using urate-lowering therapies appropriately to prevent further attacks and joint damage. The gold standard diagnostic tool for gout remains the identification by polarised light microscopy of monosodium urate crystals in synovial fluid or in a tophus. Emerging diagnostic imaging techniques and novel therapies show promise in the diagnosis and treatment of gout. In most cases, using existing therapies judiciously remains the key determinant of success in managing gout.

Topics: Allopurinol; Anti-Inflammatory Agents; Diagnostic Imaging; Gout; Humans; Synovial Fluid; Uric Acid

The central strategy for effective gout management is longterm urate-lowering therapy to maintain the serum urate at a level below 0.36 mmol/l. We sought to determine the prevalence of gout and the quality of care in a national Australian general practice population.. Data were from general practice point-of-care electronic records over a 5-year period (n = 1,479,449). Information was collected on patients with gout according to a validated definition. All patients who visited the same general practices over the study period formed the denominator group. We determined the estimated prevalence of gout, the frequency of allopurinol prescription, and serum urate testing, and the percentage of patients achieving a target serum urate level.. The crude prevalence of gout in this general practice population was 1.54% (95% CI 1.52-1.56). Prevalence in men was 2.67% and in women 0.53%. Prevalence increased with age in both men and women (4.90%, 95% CI 4.82-4.99, in men > 65 yrs). Allopurinol was prescribed to 57% of patients with gout during the 5 years of the study. Only 55% of patients with gout had their serum urate tested at any time during the 5-year study period. A target serum urate concentration of < 0.36 mmol/l at any time during the 5-year study period was documented in 22.4% of all people with gout.. Gout is managed poorly in Australian primary care, with low levels of allopurinol prescribing and serum urate testing. Collectively, these factors probably contribute to low achievement of serum urate targets.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Australia; Electronic Health Records; Female; General Practice; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prevalence; Quality of Health Care; Sex Factors; Uric Acid; Young Adult

Topics: Female; Gout; Gout Suppressants; Heart Diseases; Humans; Male; Xanthine Oxidase

Gout is a potentially destructive inflammatory disorder occurring in the setting of hyperuricaemia and urate crystal deposition in tissue. It is often overlooked or treated insufficiently. Early diagnosis is important to prevent joint destruction and to prevent the systemic effects of inflammatory disease. This is a case report of a 48-year-old male with intermittent swellings of both wrists where polarized microscopy was unable to confirm the diagnosis. Dual-energy computed tomography showed urate crystals in both wrists, and urate lowering therapy normalised the plasma urate levels. The patient was without joint swellings or pain.

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Male; Middle Aged; Radiography, Dual-Energy Scanned Projection; Tomography, X-Ray Computed; Uric Acid; Wrist Joint

Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

Topics: Aged; Allopurinol; Biomarkers; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Thyrotropin; Time Factors; Treatment Outcome; Up-Regulation; Uric Acid; Xanthine Dehydrogenase

To evaluate the efficacy and safety of the initiation time of urate-lowering treatments (ULT) in gout patients.. We retrospectively reviewed patients who were diagnosed with gout and were treated with ULT for at least 3 years. They were divided into two groups: group 1: 123 patients initiating ULT during an acute attack of gout; group 2: 457 patients prescribed ULT after an acute attack. Both demographic and clinical characteristics associated with gout were analyzed.. Comparing patients in group 1 versus group 2: the former exhibited a shorter duration of gout (6.3±2.1 vs. 8.9±3.3 years). At the baseline, there was no significant difference in mean serum urate (SU; 7.8±1.4mg/dL vs. 7.9±1.9mg/dL, respectively). SU target levels (<6.0mg/dL) were achieved by 66.7 and 65.6% of the patients, respectively. The duration from initiation of ULT until the SU target was attained was lower in group 1 than in group 2. During the first 12 weeks, patients on ULT in group 1 had higher attack rates than those in group 2. The incidence of chronic kidney disease increased in percentage in group 1 was lower than in group 2.. Our survey revealed that in patients experiencing acute gout, initiation of ULT decreased the time required to reach the target SU and the incidence of CKD, but the attack rate was greater in the first 12 weeks.

Topics: Adult; Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Uric Acid

Using a Danish Register cohort of 86,039 adult new allopurinol users and propensity score matched controls, we found that gout requiring allopurinol prescription was associated with an increased fracture risk.. Gout, an acute inflammatory arthritis, is common and associated with elevated serum urate, obesity and high alcohol consumption. The mainstay of therapy is the urate-lowering agent, allopurinol. Here, we report the relationship between allopurinol prescription and fracture in a large registry population.. We established a Danish Register cohort of 86,039 adult cases (new allopurinol users) and 86,039 age, sex and propensity score matched controls (not exposed to allopurinol or with a gout diagnosis), with no diagnosis of malignancy in the year prior.. We found a modest adjusted effect of allopurinol prescription on major osteoporotic fractures (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.05-1.14, p = 0.04) and on hip fractures (HR 1.07, 95 % CI 1.11-1.14, p < 0.001), robust to adjustment for confounding factors (age, sex, comorbidity, medication use). Associations were stronger in men than women, and among incident allopurinol users whose gout diagnosis had been confirmed by at least one hospital contact. Prespecified subanalyses by filled dose of allopurinol (mg/day in first year of prescription) showed increased hip and major fracture risk in women in the highest allopurinol dose grouping only, while a less strong dose effect was evident for fracture rates in men.. Gouty arthritis requiring allopurinol is associated with an excess risk of major or hip fracture, with an allopurinol dose effect evident in women such that women taking the highest doses of allopurinol--suggestive of more severe disease--were at increased risk relative to women taking lower doses.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Denmark; Female; Gout; Gout Suppressants; Hip Fractures; Humans; Male; Matched-Pair Analysis; Middle Aged; Osteoporotic Fractures; Propensity Score; Proportional Hazards Models; Registries; Risk Factors; Uric Acid

In most cases (98-99 %) primary hyperuricemia is caused by impaired renal excretion of uric acid. Overproduction of uric acid is rare. Secondary hyperuricemia has to be differentiated from primary forms. Clinical manifestations of hyperuricemia are acute inflammatory arthritis, tenosynovitis, bursitis, chronic arthropathy and accumulation of urate crystals in the form of tophaceous deposits. In addition renal complications can occur. Pathophysiology and diagnosis of gout were described. Treatment of gout has two goals: Treatment of the acute gout attack, to terminate pain and disability and treatment of hyperuricemia by lifestyle modification and with urate lowering drugs. A serum uric acid value below 6 mg/dl (360 µmol/L) should be achieved.

Topics: Allopurinol; Arthritis, Gouty; Colchicine; Diagnosis, Differential; Drug Therapy, Combination; Furosemide; Gout; Humans; Hyperuricemia; Life Style; Male; Middle Aged

Allopurinol is an efficacious urate-lowering therapy (ULT), but is associated with rare serious adverse drug reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with higher risk among HLA-B*5801 carriers. We assessed the cost-effectiveness of HLA-B*5801 testing, an enhanced safety program or strategies with both components.. The analysis adopted a health systems perspective and considered Singaporean patients with chronic gout, over a lifetime horizon, using allopurinol or probenecid. The model incorporated SJS/TEN and gout treatment outcomes, allele frequencies, drug prices and other medical costs.. Based on cost-effectiveness threshold of US$50,000 per quality-adjusted life year, HLA-B*5801-guided ULT selection or enhanced safety program was not cost effective. Avoidance of ULTs was the least preferred strategy as uncontrolled gout leads to lower quality-adjusted life years and higher costs.. The analysis underscores the need for biomarkers with higher positive predictive value for SJS/TEN, less expensive genetic tests or safety programs, or more effective gout drugs. .

Topics: Allopurinol; Cost-Benefit Analysis; Genotype; Genotyping Techniques; Gout; Gout Suppressants; HLA-B Antigens; Humans; Patient Safety; Singapore

The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat.. In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers.. The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2) mg/dL versus 0.4 (SD, 1.7) mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher).. In this "real-world" setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol.

Topics: Adult; Aged; Allopurinol; Comparative Effectiveness Research; Drug Monitoring; Drug Substitution; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Arthritis, Gouty; Benzbromarone; Combined Modality Therapy; Febuxostat; Female; Gout; Gout Suppressants; Humans; Middle Aged; Polyethylene Glycols; Urate Oxidase

The prevalence of gout and hyperuricemia are on the rise in the United States corresponding with an increase in risk factors for these conditions, such as obesity, metabolic syndrome, and the use of diuretics. A progressive disorder, untreated gout can be debilitating and result in tophi, chronic arthropathy, and recurrent kidney stones. Although joint aspiration is needed for a definitive diagnosis, the majority of patients are diagnosed presumptively based on medical history and presentation with characteristic signs and symptoms. Patients with gout also often have multiple comorbidities, and there is an increasing body of evidence that shows hyperuricemia is associated with incidence hypertension, diabetes, chronic kidney disease, and heart failure. Clinical strategies for the management of gout and hyperuricemia must include considerations for these and other common cardiometabolic and renal conditions. In addition to acute flare therapy and prophylaxis, the treatment of gout involves lowering serum uric acid (SUA) levels with the urate-lowering therapies (ULTs) allopurinol or febuxostat. Once begun, treatment with ULT is lifelong. However, inadequate dosing and patient nonadherence or intolerance to therapy often lead to treatment failure. Recent guidelines from the American College of Rheumatology stress tailoring therapy and target SUA level (traditionally <6 mg/dL, but lower levels may be needed for certain patients) based on gout severity and the presence of comorbid conditions. Because painful acute gout flares may result in trips to the emergency department and because the majority of gout cases are managed in primary care, it is important for clinicians practicing in these settings to be able to diagnose and treat this condition and communicate with patients to improve their understanding of the disease process and adherence to treatment.

Topics: Allopurinol; Comorbidity; Disease Management; Drug Administration Schedule; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Medication Adherence; Primary Health Care; Risk Factors; Severity of Illness Index; Thiazoles; United States; Uric Acid

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD.

Topics: Aged; Allopurinol; Bone Density; Cohort Studies; Gout; Hip Fractures; Humans; Incidence; Male; Osteoporotic Fractures; United States; Uric Acid

Allopurinol is effective for the control of gout and its long-term complications when taken consistently. There is evidence that adherence to allopurinol therapy varies across population groups. This may exacerbate differences in the burden of gout on population groups and needs to be accurately assessed. The aim of this study was to describe the prevalence of allopurinol use in a region of New Zealand using community pharmacy dispensing data and to examine the levels of suboptimal adherence in various population groups. Data from all community pharmacy dispensing databases in a New Zealand region were collected for a year covering 2005/2006 giving a near complete picture of dispensings to area residents. Prevalence of allopurinol use in the region by age, sex, ethnicity and socioeconomic position was calculated. Adherence was assessed using the medication possession ratio (MPR), with a MPR of 0.80 indicative of suboptimal adherence. Multiple logistic regression was used to explore variations in suboptimal adherence across population groups. A total of 953 people received allopurinol in the study year (prevalence 3%). Prevalence was higher in males (6%) than in females (1%) and Māori (5%) than non-Māori (3%). The overall MPR during the study was 0.88, with 161 (22%) of patients using allopurinol having suboptimal adherence. Non-Māori were 54% less likely to have suboptimal allopurinol adherence compared to Māori (95% CI 0.30-0.72, p = 0.001). These findings are consistent with those from other studies nationally and internationally and point to the important role for health professionals in improving patient adherence to an effective gout treatment.

Topics: Adult; Aged; Allopurinol; Community Pharmacy Services; Cross-Sectional Studies; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; New Zealand; Odds Ratio; Population Groups; Prevalence

The study objective was to determine the feasibility of using a pharmacist-staffed, protocol-based structured approach to improving the management of chronic, recurrent gout.. The study was carried out in the outpatient clinic of a single Kaiser Permanente medical centre. This is a community-based clinic.. We report on 100 consecutive patients between the ages of 21 and 94 (75% men) with chronic or recurrent gout, referred by their primary physicians for the purpose of management of urate-lowering therapy. Patients with stage 5 chronic kidney disease or end-stage kidney disease were excluded.. The programme consisted of a trained clinical pharmacist and a rheumatologist. The pharmacist contacted each patient by phone, provided educational and dietary materials, and used a protocol that employs standard gout medications to achieve and maintain a serum uric acid (sUA) level of 6 mg/dL or less. Incident gout flares or adverse reactions to medications were managed in consultation with the rheumatologist.. The primary outcome measure was the achievement and maintenance of an sUA of 6 or less for a period of at least 3 months.. In 95 evaluable patients enrolled in our pilot programme, an sUA of 6 mg/dL or less was achieved and maintained in 78 patients with 4 still in the programme to date. Five patients declined to participate after referral, and another 13 patients did not complete the programme. (The majority of these were due to non-adherence.). A structured pharmacist-staffed programme can effectively and safely lower and maintain uric acid levels in a high percentage of patients with recurrent gout in a primary care setting. This care model is simple to implement, efficient and warrants further validation in a clinical trial.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Ambulatory Care Facilities; Chronic Disease; Feasibility Studies; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Patient Care Planning; Pharmacy Service, Hospital; Pilot Projects; Treatment Outcome; Uric Acid

Topics: Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Recombinant Fusion Proteins; Urate Oxidase

European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels.. The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients.. Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal.. Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients.

Topics: Aged; Allopurinol; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged

Limited literature exists for qualitative studies of medication adherence in gout, especially in African-Americans. The aim of this study was to examine the facilitators and barriers to adherence to urate-lowering therapy (ULT) in African-Americans with gout.. In this study, nine nominal groups lasting 1 to 1.5 hours each were conducted in African-Americans with gout, six with low ULT and three with high ULT adherence (medication possession ratios of <0.80 or ≥0.80, respectively). Patients presented, discussed, combined and rank ordered their concerns. A qualitative analysis was performed.. This study included 43 patients with mean age 63.9 years (standard deviation, 9.9), 67% men, who participated in nine nominal groups (seven in men, two in women): African-American men (n = 30); African-American women (n = 13). The main facilitators to ULT adherence (three groups) were the recognition of the need to take ULT regularly to prevent gout flares, prevent pain from becoming chronic/severe and to have less dietary restriction; the lack of side effects from ULT; trust in physicians; and avoiding the need to seek emergent/urgent care for flares. Patients achieved high ULT adherence by organizing their pills using the pillbox and the incorporation of ULT intake into their routine to prevent forgetting. The main barriers to optimal ULT adherence were (six groups): doubts about effectiveness of ULT, concerns about cost and side effects, concomitant medications, forgetfulness, refilling the prescriptions on time, pill size and difficulty in swallowing, competing priorities, patient preference for alternative medicines (that is, cherry juice) and frequent travel.. Identification of facilitators and barriers to high ULT adherence in African-Americans with gout in this study lays the foundation for designing interventions to improve ULT adherence in racial minorities.

Topics: Aged; Allopurinol; Black or African American; Evaluation Studies as Topic; Febuxostat; Female; Focus Groups; Gout; Gout Suppressants; Health Knowledge, Attitudes, Practice; Humans; Male; Medication Adherence; Middle Aged; Thiazoles; Uric Acid

Febuxostat is recommended as 1 of 2 first-line urate-lowering therapies (ULT) for treating gout in the 2012 American College of Rheumatology Guidelines. Several efficacy trials have compared febuxostat with allopurinol treatment, but real-world comparative data are limited.. We compared effectiveness of the 2 agents in reaching serum urate (sUA) level goal (< 6 mg/dL) within 6 months (main endpoint), factors impacting the likelihood of reaching goal, and outcomes in allopurinol patients who were switched to febuxostat therapy after failing to reach sUA level goal. Data from the General Electric Electronic Medical Record database on adult patients with newly diagnosed gout, who had started treatment with allopurinol or febuxostat in 2009 or thereafter were analyzed. Descriptive statistics, bivariate analyses, and logistic regressions were used.. Allopurinol (n = 17 199) and febuxostat (n = 1190) patients had a mean ± standard deviation (SD) age of 63.7 (± 13.37) years; most patients were men and white. Average daily medication doses (mg) in the first 6 months were 184.9 ± 96.7 and 48.4 ± 15.8 for allopurinol- and febuxostat-treated patients, respectively; 4.8% of allopurinol-treated patients switched to febuxostat, whereas 25.7% of febuxostat-treated patients switched to allopurinol. Febuxostat patients had lower estimated glomerular filtration rate levels, more diabetes mellitus, or tophi at baseline (P < 0.05) and 29.2% and 42.2% of patients in the allopurinol and febuxostat groups achieved goal sUA levels (P < 0.0001). Febuxostat was significantly more effective in patients reaching sUA goal (adjusted odds ratio, 1.73; 95% CI, 1.48-2.01). Older patients and women had greater likelihood of reaching sUA goal level; however, patients with higher Charlson Comorbidity Index scores, blacks, or those with estimated glomerular filtration rates between 15 to ≤ 60 mL/min had reduced likelihood of attaining goal (P < 0.05). Among allopurinol-treated patients who were switched to febuxostat after failing to reach goal, 244 (48.3%) reached goal on febuxostat (median = 62.5 days), with an average 39% sUA level reduction achieved within 6 months. Patients who did not reach goal had a 14.3% sUA level reduction.. The real-life data support the effectiveness of febuxostat in managing patients with gout.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Biomarkers; Comparative Effectiveness Research; Drug Administration Schedule; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Logistic Models; Male; Middle Aged; Retrospective Studies; Thiazoles; Treatment Outcome; Uric Acid; Young Adult

Topics: Aged; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Guideline Adherence; Hospitalization; Humans; Hyperuricemia; Male; Prevalence; Thiazoles; Xanthine Oxidase

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Colchicine; Enzyme Inhibitors; Gout; Gout Suppressants; Humans; Interleukin-1; Secondary Prevention; Treatment Outcome; Uric Acid; Uricosuric Agents; Xanthine Oxidase

Currently, natural products have been used in treating gouty arthritis and are recognized as xanthine oxidase inhibitors. Current study was designed to evaluate in vitro xanthine oxidase inhibitory potential of Gouticin and its ingredients extracts and in vivo hypouricemic activity of gouticin tablet 500 mg twice daily. Ethanol extracts of Gouticin and its ingredients were evaluated in vitro, at 200, 100, 50, 25 μ g/ml concentrations for xanthine oxidase inhibitory activity. IC(50) values of Gouticin and its ingredients were estimated. Further, in vivo therapeutic effect of Gouticin was investigated in comparison with allopathic medicine (Allopurinol) to treat gout. Total patients were 200 that were divided into test and control group. Herbal coded medicine (Gouticin) was given to test group and allopathic medicine allopurinol was administered to control group. In vitro, Gouticin has the highest percent inhibition at 96% followed by Allopurinol with 93% inhibition. In vivo study, mean serum uric acid level of patients was 4.62 mg/dl and 5.21mg/dl by use of Gouticin and Allopurinol at end of therapy. The study showed that herbal coded formulation gouticin and its ingredients are potential sources of natural xanthine oxidase inhibitors. Gouticin 500 mg twice daily is more effective than the allopurinol 300mg once daily in the management of gout.

Topics: Allopurinol; Female; Gout; Humans; Male; Middle Aged; Phytotherapy; Plant Extracts; Plants, Medicinal; Uric Acid; Xanthine Oxidase

Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.

Topics: Animals; Disease Models, Animal; Euonymus; Formaldehyde; Gardenia; Gout; Hyperuricemia; Nociception; Pain; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Rubia; Taiwan; Toxicity Tests; Uric Acid; Xanthine Oxidase

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

Topics: Adult; Allopurinol; Antimetabolites; Benzbromarone; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hypertension; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Thiazoles; Uric Acid; Uricosuric Agents; Urolithiasis

As a final step of the purine metabolism process, xanthine oxidase catalyzes the oxidation of hypoxanthine and xanthine into uric acid. Our research has demonstrated that Erycibe obtusifolia has xanthine oxidase inhibitory properties. The purpose of this paper is to describe a new strategy based on a combination of multiple mass spectrometric platforms and thin-layer chromatography bioautography for effectively screening the xanthine oxidase inhibitory and antioxidant properties of E. obtusifolia. This strategy was accomplished through the following steps. (i) Separate the extract of E. obtusifolia into fractions by an autopurification system controlled by liquid chromatography with mass spectrometry. (ii) Determine the active fractions of E. obtusifolia by thin-layer chromatography bioautography. (iii) Identify the structure of the main active compounds with the information provided by direct analysis in real time mass spectrometry. (iv) Calculate the IC50 value of each compound against xanthine oxidase using high-performance liquid chromatography. Using the caulis of E. obtusifolia as the experimental material, seven target peaks were screened out as xanthine oxidase inhibitors or antioxidants. Our screening strategy allows for rapid analysis of small molecules with almost no sample preparation and can be completed within a week, making it a useful assay to identify unstable compounds and provide the empirical foundation for E. obtusifolia as a natural remedy for gout and oxidative-stress-related diseases.

Topics: Antioxidants; Automation; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Thin Layer; Drug Design; Enzyme Inhibitors; Gout; Inhibitory Concentration 50; Mass Spectrometry; Oxidative Stress; Plant Extracts; Tropanes; Xanthine Oxidase

Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.. Patients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.. With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08-1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10-1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73-0.95) for cardiovascular events compared with the allopurinol group.. The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Survival Rate

Allopurinol (AP) inhibits the xanthine oxidase, which may indirectly lead to myelotoxicity when used in combination with azathioprine (AZA).. A 79-year-old female developed symptomatic thrombocytopenia after combination therapy with AZA (75 mg/day) and AP (100 mg/day) - after AP had been stopped. Concentrations of the myelotoxic 6-thioguanine-nucleotides metabolite of AZA were increased. Thrombocyte counts normalized within 8 days of discontinuation of AZA.. The effect of a drug interaction in a patient with decreased elimination capacity may take several weeks to become apparent and may in fact do so even after the drug has been stopped. Concurrent AZA and AP therapy demands cautious use.

Topics: Aged; Allopurinol; Azathioprine; Diagnosis, Differential; Female; Gout; Gout Suppressants; Humans; Immunosuppressive Agents; Kidney Transplantation; Severity of Illness Index; Thrombocytopenia

Gout patients receiving a combination of allopurinol and furosemide require higher allopurinol doses to achieve the target serum urate (SU) of <6 mg/dl (Stamp et al., 2012) [1]. Our study aimed to identify the molecular basis for this observation. We used a fluorimetric assay to determine the impact of furosemide and oxypurinol (the active metabolite of allopurinol) on xanthine oxidase (XO) activity. Immunoblot analysis quantified expression of XO and AMP-kinase (AMPK) in drug-treated human liver (HepG2) and primary kidney (HRCE) cells. In silico analysis identified miR-448 as a potential XO-regulator, whose expression level in HepG2 cells was examined by qPCR. Fluorimetric experiments revealed no direct interactions between XO and furosemide, nor did the combination of oxypurinol/furosemide alter the XO inhibition profile of oxypurinol. In HepG2 cells, we found a significant decrease in XO protein expression following oxypurinol treatment, which was abolished after co-incubation with furosemide. Probenecid alone or in combination with furosemide reduced XO protein expression significantly. qPCR analysis of miR-448 in HepG2 cells mirrored the drug-dependent changes in XO protein expression. In addition, oxypurinol and the combination of oxypurinol/furosemide significantly down-regulated AMPK protein expression in HRCE cells. In conclusion, we show for the first time that besides the established effects of allopurinol on the purine synthetic pathway the efficiency of allopurinol treatment of gout patients is based on two further complementary mechanisms, the direct inhibition of XO activity by the allopurinol metabolite oxypurinol and a down-regulation of XO protein expression. The latter is compromised by addition of furosemide and might explain why patients receiving furosemide therapy require higher allopurinol doses. miR-448 was identified as a potential drug-dependent XO regulator. Finally, down-regulation of AMPK protein expression in HRCE cells by administration of oxypurinol/furosemide reveals a possible new mechanism of renal drug-induced hyperuricemia.

Topics: Allopurinol; Cell Line; Drug Interactions; Furosemide; Gout; Humans

Topics: Aged; Allopurinol; Colchicine; Comorbidity; Disease Progression; Gout; Gout Suppressants; Hand Joints; Humans; Male; Osteoarthritis; Rheumatic Nodule

Ramadan fast is a religious custom in Islam. Increased serum uric acid level during this month had been reported in past studies of nongout patients.. The objective of this study was to assess the impact of Ramadan fast on patients with gout.. All Moslem patients with gout from the registry of Nazareth Hospital, who intended to fast during Ramadan, were asked to participate in our study (group 1). Data regarding age, gender, income, education, duration of gout, meds, adherence to low-purine diet, and gouty attacks were documented. Age- and gender matched Moslem patients from the same registry, but who did not intend to fast during Ramadan, were asked to participate as a control group (group 2). Just prior to and at the end of Ramadan, blood for uric acid, creatinine, and urea levels were obtained as well as body mass index, from all the patients. During Ramadan, patients were monitored for gouty arthritis or renal calculi attacks, as well as low-purine diet and medicine adherence.. Twenty-one and 22 patients from groups 1 and 2, respectively, completed the study. Mean serum uric acid, urea, creatinine, and body mass index levels at the end of Ramadan fasts in group 1 patients were 8.11 mg/dL, 26.38 mmol/L, 0.87 mg/dL, and 31.0 kg/m, respectively, as compared with 7.92 mg/dL (P = 0.707), 24.54 mmol/L (P = 0.769), 0.84 mg/dL (P = 0.180), and 30.5 kg/m (P = 0.907) respectively, obtained just prior to the fast. No significant change in any parameter was seen also in group 2 patients. There also was no significant change between the 2 groups in arthritis or renal calculi attacks and also in medication and low-purine diet adherence, during Ramadan.. There was no risk for a significant increase in gouty arthritic/renal calculi attacks or serum uric acid in patients with gout during Ramadan fast.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Body Mass Index; Case-Control Studies; Colchicine; Creatinine; Fasting; Female; Gout; Gout Suppressants; Humans; Islam; Israel; Male; Middle Aged; Patient Compliance; Urea; Uric Acid

To examine whether there was variation in markers for the quality of gout care using national linked data for the entire Aotearoa New Zealand population.. Data drawn for the New Zealand Atlas of Healthcare Variation was used to examine regularity of allopurinol dispensing, laboratory testing for serum urate, and acute hospitalisation for gout. Standardised rates by age, gender, ethnicity and District Health Board (DHB) of domicile were calculated.. For New Zealanders aged 20-79 years with gout, 57% were dispensed allopurinol in 2010/11. Of these, 69% were receiving allopurinol regularly, and only 34% of people dispensed allopurinol had serum urate testing in a 6-month period. The annual hospitalisation rate was 1% of people with gout. Maori and Pacific people with gout were less likely to be on regular allopurinol treatment, despite having more than twice the chance of being hospitalised with acute gout.. We have demonstrated that routinely collected health data can be used to monitor the quality of care for people with gout at a high level. Primary care initiatives that focus on ensuring a continuous supply of urate-lowering therapy to achieve therapeutic serum urate targets are required to improve the impact of gout in Aotearoa New Zealand.

Topics: Adult; Aged; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; New Zealand; Practice Patterns, Physicians'; Quality Indicators, Health Care

Gout is the most common inflammatory arthritis in the United States.. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout.. Markov model.. Published literature and expert opinion.. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment.. Lifetime.. Health care payer.. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate).. Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios.. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year.. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year.. Long-term outcome data for patients with gout, including medication adherence, are limited.. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds.. Agency for Healthcare Research and Quality.

Topics: Allopurinol; Cost Savings; Cost-Benefit Analysis; Drug Therapy, Combination; Febuxostat; Gout; Gout Suppressants; Humans; Markov Chains; Models, Theoretical; Quality-Adjusted Life Years; Thiazoles

Gout is a metabolic disorder associated with hyperuricemia resulting in the deposition of monosodium urate (MSU) crystals in joints and tissues. Lowering serum uric acid (Sur) levels and anti-inflammation are highly essential in treating gout. Chlorogenic acid (CA), as one of the most abundant polyphenols in the Chinese medicines, has been rarely reported to have an anti-gout effect. The model of potassium oxonate (PO)-induced hyperuricemia in mice and MSU crystal-induced inflammation in rats has been established in this study. The potential beneficial effects and mechanisms of CA on hyperuricemia and gouty arthritis were elucidated. The results demonstrated that CA significantly decreased the Sur level by inhibiting the xanthine oxidase (XOD) activity but not increasing the urinary uric acid (Uur) level. In addition, CA also exhibited the effect of suppressing paw swelling. Further investigation indicated that CA improved the symptoms of inflammation induced by MSU crystals by inhibiting the production of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The present study suggests that CA may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.

Topics: Animals; Chlorogenic Acid; Cytokines; Disease Models, Animal; Gout; Gout Suppressants; Hyperuricemia; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Male; Mice, Inbred Strains; Phytotherapy; Tumor Necrosis Factor-alpha; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Diagnosis, Differential; Female; Fingers; Gout; Gout Suppressants; Humans; Middle Aged; Skin Ulcer

We report 2 cases of familial juvenile hyperuricemic nephropathy, a rare autosomal dominant disorder characterized by uromodulin gene mutations leading to hyperuricemia secondary to profound renal uric acid underexcretion, gout, and chronic renal disease. Case 1 involves a 56-year-old woman who underwent a kidney transplant after steady decline in kidney function since the age of 19 years. Her gout had been successfully controlled with varying doses of daily allopurinol. Case 2, the son of case 1, presented with already progressive and debilitating arthritis at the age of 34 years with relatively stable chronic renal failure that was also subsequently managed with daily allopurinol and judicious anti-inflammatory prophylaxis.

Topics: Adult; Allopurinol; Arthritis, Gouty; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Gout; Graft Survival; Humans; Hyperuricemia; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Pedigree; Sampling Studies; Severity of Illness Index; Treatment Outcome

Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards.. While the prevalence of gout was calculated by counting patients with this diagnosis hyperuricemia was inferred in patients taking allopurinol at hospital admission or discharge, on the assumption that this drug was only prescribed owing to the finding of high serum levels of uric acid. A series of clinical and demographic variables were evaluated for their association with gout/hyperuricemia.. Of 1380 patients, 139 (10%) had a diagnosis of gout or were prescribed allopurinol. They had more co-morbidities (7.0 vs 5.6; P<0.0001) and consumed more drugs (6.8 vs 5.0; P<0.0001). The CIRS (co-morbidity index) was worse in these patients (OR 1.28 95% CI 1.15-1.41). Multivariable regression analysis showed that only renal and heart failures were independently associated with gout/allopurinol intake. Moreover, this combined event was associated with an increased risk of adverse events during hospitalization (OR 1.66, 95% CI 1.16-2.36), but not with the risk of re-hospitalization, length of hospital stay or death.. Gout/allopurinol intake has a high prevalence in elderly patients acutely admitted to hospital and are associated with renal and cardiovascular diseases, an increased rate of adverse events and a high degree of drug consumption. In contrast, this finding did not affect the length of hospitalization nor hospital mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Chronic Disease; Comorbidity; Female; Gout; Hospital Mortality; Hospitalization; Humans; Hyperuricemia; Kidney Diseases; Length of Stay; Male; Treatment Outcome; Uric Acid

Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events. To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study. Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P = .005), more hypertension (42% vs 30%, P = .036), less tumor lysis syndrome (P = .030), higher cholesterol (P = .013), and lower aspartate aminotransferase (P = .002) and alanine aminotransferase levels (P = .033) and more commonly used angiotensin receptor blockers (27% vs 15%, P = .007), colchicines (16% vs 5%, P = .010), or statins (19% vs 8%, P = .002) than those who did not. In multiple logistic regression analysis, the use of colchicines (odds ratio, 3.11; 95% confidence interval, 1.28-7.58; P = .012) and statins (2.10; 1.03-4.25; P = .041) was an independent risk factor predicting adverse events in allopurinol users. In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events.

Topics: Adult; Aged; Allopurinol; Colchicine; Drug-Related Side Effects and Adverse Reactions; Female; Gout; Gout Suppressants; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertension; Hyperuricemia; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Young Adult

The aims of this study were to develop a population pharmacokinetic model for allopurinol and oxypurinol and to explore the influence of patient characteristics on allopurinol and oxypurinol pharmacokinetics.. Data from 92 patients with gout and 12 healthy volunteers were available for analysis. A parent-metabolite model with a two-compartment model for allopurinol and a one-compartment model for oxypurinol was fitted to the data using non-linear mixed effects modelling.. Renal function, fat-free mass (FFM) and diuretic use were found to predict differences in the pharmacokinetics of oxypurinol. The population estimates for allopurinol clearance, inter-compartmental clearance, central and peripheral volume were 50, 142 L/h/70 kg FFM, 11.4, 91 L/70 kg FFM, respectively, with a between-subject variability of 33 % (coefficient of variance, CV) for allopurinol clearance. Oxypurinol clearance and volume of distribution were estimated to be 0.78 L/h per 6 L/h creatinine clearance/70 kg FFM and 41 L/70 kg FFM in the final model, with a between-subject variability of 28 and 15 % (CV), respectively.. The pharmacokinetic model provides a means of predicting the allopurinol dose required to achieve target oxypurinol plasma concentrations for patients with different magnitudes of renal function, different body mass and with or without concomitant diuretic use. The model provides a basis for the rational dosing of allopurinol in clinical practice.

Topics: Allopurinol; Body Composition; Cohort Studies; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Humans; Male; Metabolic Clearance Rate; Models, Biological; Oxypurinol; Xanthine Oxidase

Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase-2 enzymes. In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the IGEMDOCK software tool against the xanthine oxidase and cyclooxygenase-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2. Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase-2 as demonstrated by IC(50): 62.7 and 3.29 μg/mL (xanthine oxidase)/70.8 and 16.38 μg/mL (cyclooxygenase-2), respectively. In addition, structure-activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2 were discussed, which is expected for further rational drug design.

Topics: Binding Sites; Biological Assay; Cyclooxygenase 2; Databases, Chemical; Drug Design; Enzyme Inhibitors; Flavonoids; Gout; Humans; Isoflavones; Molecular Docking Simulation; Protein Structure, Tertiary; Software; Structure-Activity Relationship; Xanthine Oxidase

Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout.. The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales.. The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout.. The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.

Topics: Adrenal Cortex Hormones; Advisory Committees; Alcoholic Beverages; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Combined Modality Therapy; Dairy Products; Disease Management; Evidence-Based Medicine; Febuxostat; Female; Fructose; Gout; Humans; Italy; Male; Risk Factors; Smoking; Societies, Medical; Thiazoles; Uric Acid

Acute monoarthritis is a common medical emergency with wide differential diagnosis. Common underlying causes include trauma, septic arthritis, crystal induced arthritis (gout and pseudogout), and reactive arthritis. Of these, septic arthritis is the diagnosis not to miss because of its association with significant morbidity and mortality. Precise diagnosis of the underlying cause of monoarthritis relies on a good history, physical examination findings, and results of focussed investigations. In this article, a practical approach to diagnosis and initial management of patients presenting with acute monoarthritis is described with the aid of a case vignette.

Topics: Acute Disease; Adult; Allopurinol; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Colchicine; Diagnosis, Differential; Diclofenac; Floxacillin; Gout; Gout Suppressants; Hematologic Tests; Humans; Male; Physical Examination; Synovial Fluid

We report for the first time the lack of therapeutic effects after the switch from a brand formulation of allopurinol to a generic one. A 56-year-old man, with a 5 years history of well-treated gout arthropathy with allopurinol (Zyloric(®) 300 mg/die), developed acute gout arthropathy after the switch from the brand formulation of allopurinol to a generic one. Clinical evaluation and laboratory findings confirmed the diagnosis of acute gout arthropathy. Generic formulation of the drug was dismissed and Zyloric(®) was administered with an improvement of both clinical symptoms and laboratory findings. In conclusion, even if generic formulations are considered to have the same effects in comparison to the brand one, more data are necessaries in order to well define their effectiveness and rationale use.

Topics: Allopurinol; Drugs, Generic; Excipients; Gout; Gout Suppressants; Humans; Male; Middle Aged

Topics: Allopurinol; Enzymes, Immobilized; Gout; Gout Suppressants; Humans; Patient Education as Topic; Polyethylene Glycols; Treatment Outcome; Urate Oxidase

Allopurinol is a purine analogue that inhibits xanthine oxidase. It is mainly used for the treatment of hyperuricemia in patients with gout or tumor lysis syndrome. Experience with allopurinol in pregnancy is scarce. In 2011, Kozenko et al. reported on a child with multiple malformations after maternal treatment with allopurinol throughout pregnancy. Possible teratogenicity of allopurinol was proposed due to the similarity of the pattern of malformations in children with mycophenolate embryopathy. A possible common mechanism of both drugs, i.e. disruption of purine synthesis, was discussed. We report on the outcome of 31 prospectively ascertained pregnancies with allopurinol exposure at least during first trimester. Pregnancy outcomes were 2 spontaneous abortions, 2 elective terminations of pregnancy and 27 live born children. The overall rate of major malformations (3.7%) and of spontaneous abortions (cumulative incidence 11%, 95%-CI 3-40) were both within the normal range. However, there was one child with severe malformations including microphthalmia, cleft lip and palate, renal hypoplasia, low-set ears, hearing deficit, bilateral cryptorchidism, and micropenis. The striking similarity of the anomalies in this child and the case described by Kozenko et al. might be considered as a signal for teratogenicity. Thus, we would recommend caution with allopurinol treatment in the first trimester, until further data are available.

Topics: Abortion, Therapeutic; Allopurinol; Female; Gout; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Teratogens; Tumor Lysis Syndrome

This study aims to investigate the disease-related knowledge of gout patients and doctors in south China and to identify the important targets of education for patients and doctors. A cross-section survey of 154 primary gout patients and 185 doctors who may see gout patients was conducted with a modified questionnaire with ten items of gout-related knowledge. The participants were considered to have gout-related knowledge if he or she correctly answered seven or more items. One hundred and forty-nine valid questionnaires from patients, 33 from rheumatology physicians, and 151 from non-rheumatology doctors were collected for statistical analysis. The mean correctly answered items of three groups were 6.6 ± 2.2, 9.6 ± 0.53, and 8.0 ± 1.4, with rate of being considered to have knowledge about gout 51.7, 100, and 90.1 %, respectively (P < 0.05). The correct answer rate for each particular item was over 80 % in the rheumatology physician group. Patients or non-rheumatology doctors knew the optimal serum uric acid (sUA) level (48.3 vs 55.6 %), the need to take lifelong urate-lowering drugs (29.5 vs 43.6 %), that allopurinol is a urate-lowering drug (55.7 vs 76.0 %), and how to prevent attacks induced by urate-lowering therapy (ULT) (60.4 vs 74.0 %). Logistic regression showed that higher education predicted which patients had gout-related knowledge. Both the gout patients and non-rheumatology doctors in south China had poor knowledge on ULT. Since many gout patients do not see rheumatologists, our data suggest that further education should focus on patients and non-rheumatologists and emphasize the use of urate-lowering drugs, treatment duration, the target sUA level, and prophylaxis against acute attacks.

Topics: Adult; Aged; Allopurinol; Arthritis, Gouty; China; Cross-Sectional Studies; Female; Gout; Gout Suppressants; Health Knowledge, Attitudes, Practice; Humans; Hyperuricemia; Male; Middle Aged; Physicians; Rheumatology; Surveys and Questionnaires

Gout is a common form of inflammatory arthritis with an increasing prevalence in developed countries. It is well known that many patients with gout have significant comorbidities and high health care utilization. We aimed to describe the clinical characteristics and health care utilization patterns in patients with gout who were newly prescribed allopurinol, febuxostat, or colchicine.. We used US insurance claims data (2009-2011) to conduct a population-based cohort study.. There were 25,051 allopurinol, 4,288 febuxostat, and 6,238 colchicine initiators. The mean age was 53 years and 83-87% were men. More than one-half of the patients had hypertension and hyperlipidemia, 20% had diabetes mellitus, and 10% had cardiovascular disease. The mean uric acid level was similar across the groups at baseline, ranging from 8.1-8.5 mg/dl. Compared with allopurinol or colchicine initiators, febuxostat initiators had more comorbidities and greater health care utilization, including outpatient, inpatient, or emergency room visits, both at baseline and during followup. Use of gout-related drugs such as opioids, steroids, and nonsteroidal antiinflammatory drugs was most common in febuxostat initiators and least common in colchicine initiators. The median daily doses at both the start and end of treatment were 300 mg for allopurinol, 40 mg for febuxostat, and 1.2 mg for colchicine. The doses of allopurinol and febuxostat were rarely increased during followup.. Patients who started allopurinol, febuxostat, or colchicine for gout generally had hyperuricemia and multiple comorbidities. Febuxostat initiators had more comorbidities and greater use of health care resources and gout-related drugs than the other groups. Overall, the doses of allopurinol or febuxostat remained unchanged over time.

Topics: Allopurinol; Ambulatory Care; Colchicine; Comorbidity; Febuxostat; Female; Gout; Gout Suppressants; Hospitalization; Humans; Male; Middle Aged; Office Visits; Thiazoles

Topics: Allopurinol; Benzbromarone; Colchicine; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Male; Middle Aged; Urate Oxidase

Topics: Allopurinol; Gout; Gout Suppressants; Humans; Practice Guidelines as Topic; Surveys and Questionnaires

A taste disturbance and anorexia accompanied his other symptoms. How would you proceed?

Topics: Aged, 80 and over; Allopurinol; Dehydration; Diarrhea; Drug Eruptions; Exanthema; Gout; Hawaii; Humans; Male; Oxypurinol; Risk Factors

Oxypurinol, the active metabolite of allopurinol, is the major determinant of the hypouricemic effect of allopurinol. Monitoring oxypurinol concentrations is undertaken to determine adherence to therapy, to investigate reasons for continuing attacks of acute gout and/or insufficiently low plasma urate concentrations despite allopurinol treatment, and to assess the risk of allopurinol hypersensitivity, an adverse effect that has been putatively associated with elevated plasma oxypurinol concentrations.. An audit of request forms requesting plasma oxypurinol concentration measurements received by the pathology service (SydPath) at St Vincent's Hospital, Darlinghurst, Sydney was undertaken for the 7-year period January 2005-December 2011. Patient demographics, biochemical data, including plasma creatinine and uric acid concentrations, comorbidities, and concomitant medications were recorded.. There were 412 requests for determination of an oxypurinol concentration. On 48% of occasions, the time of allopurinol dosing was recorded, while just 79 (19%) blood samples were collected 6-9 hours postdosing, the time window used to establish the therapeutic range for oxypurinol. For these optimally interpretable concentrations, 32 (8%) were within the putative therapeutic range (5-15 mg/L), while 5 (1%) were below and 41 (10%) above this range. The daily dose of allopurinol was documented on only one-third of the request forms. Individually, plasma urate and creatinine concentrations were requested concomitantly with plasma oxypurinol concentrations in 66% and 58% of the cases, respectively; while plasma oxypurinol, urate, and creatinine concentrations were requested concomitantly in 49% of the cases.. Requesting clinicians and blood specimen collectors often fail to provide relevant information (dose, times of last dose, and blood sample collection) to allow the most useful interpretation of oxypurinol concentrations. Concomitant plasma urate and creatinine concentrations should be requested to allow more complete interpretation of the data.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Child; Child, Preschool; Creatinine; Drug Monitoring; Female; Gout; Gout Suppressants; Humans; Infant; Male; Medication Adherence; Middle Aged; Oxypurinol; Time Factors; Uric Acid; Young Adult

Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout.. Seventy-three patients with tophaceous gout on stable therapy attended study visits at baseline and twelve months. All patients had a comprehensive clinical assessment including serum urate testing and DECT scanning of both feet. Two readers analysed the DECT scans for the total urate volume in both feet. Analysis included inter-reader intraclass correlation coefficients (ICCs) and limits of agreement, and calculation of the smallest detectable change.. Mean (standard deviation) serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate-lowering therapy was prescribed in 70 (96%) patients. The median (interquartile range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm(3), and change in DECT urate volume was -0.01 (-0.40, 0.28) cm(3). Inter-reader ICCs were 1.00 for baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard deviation) for baseline volumes was -0.18 (0.63) cm(3) and for change was -0.10 (0.93) cm(3). The smallest detectable change was 0.91 cm3. There were 47 (64%) patients with baseline DECT urate volumes <0.91 cm(3). Higher serum urate concentrations were observed in patients with increased DECT urate volumes above the smallest detectable change (P = 0.006). However, a relationship between changes in DECT urate volumes and serum urate concentrations was not observed in the entire group.. In patients with tophaceous gout on stable conventional urate-lowering therapy the measurement error for DECT urate volume assessment is substantially greater than the median baseline DECT volume. Analysis of patients commencing or intensifying urate-lowering therapy should clarify the optimal use of DECT as a potential outcome measure in studies of chronic gout.

Topics: Aged; Allopurinol; Female; Foot; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prospective Studies; Reproducibility of Results; Tomography, X-Ray Computed; Uric Acid

A 30-year-old man was referred for investigation and management of hyperuricaemia. History included recurrent nephrolithiasis and chronic gout with poor response to medical management. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme activity was investigated and found to be deficient confirming the diagnosis of Lesch-Nyhan disease. Hyperuricaemia was treated with allopurinol. To prevent nephrolithiasis, the patient was instructed to avoid dehydration and aim for a minimum urine output of 2 L/day. Urinary alkalinisation with potassium citrate was started. The patient was referred for genetic counselling. This case discusses the genetics, pathophysiology, clinical manifestations, diagnosis and management of HGPRT deficiency.

Topics: Adult; Allopurinol; Diuretics; Genetic Counseling; Gout; Gout Suppressants; Humans; Hyperuricemia; Hypoxanthine Phosphoribosyltransferase; Lesch-Nyhan Syndrome; Male; Nephrolithiasis; Potassium Citrate; Uric Acid

Rare but potentially life-threatening cutaneous adverse reactions have been associated with allopurinol, but population-based data on the incidence and mortality of such reactions are scarce.. We conducted a propensity score-matched cohort study to evaluate the incidence rate (IR) and in-hospital mortality of hospitalization for severe cutaneous adverse reactions (SCARs) in allopurinol initiators compared to non-allopurinol users, using data from 5 large Medicaid programs. The primary outcome was identified by the principal discharge diagnosis code 695.1. A Cox proportional hazards model evaluated the relative risk of SCARs associated with the use of allopurinol and determined the relative risk of SCARs associated with allopurinol dose.. During a followup period of 65,625 person-years for allopurinol initiators, 45 were hospitalized with SCARs. The crude IR was 0.69 (95% confidence interval [95% CI] 0.50-0.92) per 1,000 person-years. All 45 cases occurred within 365 days and 41 (91.1%) occurred within 180 days after initiating treatment with allopurinol. Twelve patients (26.7%) died during the hospitalization. The crude IR in non-allopurinol users was 0.04 (95% CI 0.02-0.08) per 1,000 person-years. The risk of SCARs was increased in allopurinol initiators versus nonusers (hazard ratio [HR] 9.68, 95% CI 4.55-20.57). Among allopurinol initiators, the HR for high-dosage (>300 mg/day) versus low-dosage allopurinol was 1.30 (95% CI 0.31-5.36) after adjusting for age, comorbidities, and recent diuretic use.. Among allopurinol initiators, SCARs were found to be rare but often fatal, and occurred mostly in the first 180 days of treatment. The risk of SCARs was 10 times as high in allopurinol initiators as compared to allopurinol nonusers.

Topics: Allopurinol; Drug Eruptions; Follow-Up Studies; Gout; Hospital Mortality; Hospitalization; Humans; Incidence; Population Surveillance; Propensity Score; Retrospective Studies; Severity of Illness Index; United States

Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even.

Topics: Allopurinol; Animals; Desensitization, Immunologic; Drug Hypersensitivity; Febuxostat; Gout; Humans; Hyperuricemia; Product Surveillance, Postmarketing; Recombinant Proteins; Skin; Thiazoles; Urate Oxidase

Topics: Allopurinol; Biomarkers; Biopsy; Bone Marrow; Bone Marrow Examination; Colchicine; Crystallization; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Immunohistochemistry; Male; Middle Aged; Panniculitis; Predictive Value of Tests; Treatment Outcome; Uric Acid

Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinolinduced SCAR. We have summarized the evidence from the published literature and developed peer-reviewed guidelines for allopurinol use based on HLA-B genotype.

Topics: Alleles; Allopurinol; Dose-Response Relationship, Drug; Genotype; Gout; Gout Suppressants; HLA-B Antigens; Humans; Hyperuricemia; Pharmacogenetics; Stevens-Johnson Syndrome

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Recombinant Fusion Proteins; Uric Acid

To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation.. The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant.. A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45-64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease.. Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Incidence; Israel; Male; Medication Adherence; Middle Aged; Prevalence; Retrospective Studies; Sex Factors; Socioeconomic Factors

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

Topics: Adult; Allopurinol; Case-Control Studies; Chronic Disease; Cohort Studies; Comorbidity; Cost of Illness; Databases, Factual; Emergency Service, Hospital; Female; Gout; Gout Suppressants; Health Care Costs; Health Services; Hospitalization; Humans; Male; Middle Aged; Prevalence; Regression Analysis; Retrospective Studies

Topics: Adult; Allopurinol; Chromatography, High Pressure Liquid; Drug Overdose; Female; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Oxypurinol; Ribonucleosides; Risk Factors; Transsexualism

Previous small studies in Aotearoa New Zealand have indicated a high prevalence of gout. This study sought to determine the prevalence of gout in the entire Aotearoa New Zealand population using national-level health data sets.. We used hospitalization and drug dispensing claims for allopurinol and colchicine for the entire Aotearoa New Zealand population from the Aotearoa New Zealand Health Tracker (ANZHT) to estimate the prevalence of gout in 2009, stratified by age, gender, ethnicity and socio-economic status (n = 4 295 296).. were compared with those obtained from an independent large primary care data set (HealthStat, n = 555 313). Results. The all-ages crude prevalence of diagnosed gout in the ANZHT population was 2.69%. A similar prevalence of 2.89% was observed in the HealthStat population standardized to the ANZHT population for age, gender, ethnicity and deprivation. Analysis of the ANZHT population showed that gout was more common in Māori and Pacific people [relative risk (RR) 3.11 and 3.59, respectively], in males (RR 3.58), in those living in the most socio-economically deprived areas (RR 1.41) and in those aged >65 years (RR >40) (P-value for all <0.0001). The prevalence of gout in elderly Māori and Pacific men was particularly high at >25%.. Applying algorithms to national administrative data sets provides a readily available method for estimating the prevalence of a chronic condition such as gout, where diagnosis and drug treatment are relatively specific for this disease. We have demonstrated high gout prevalence in the entire Aotearoa New Zealand population, particularly among Māori and Pacific people.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Colchicine; Databases, Factual; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Prevalence; Public Health; Sex Factors

There is a disproportionate burden of gout in African-Americans in the U.S. due to a higher disease prevalence and lower likelihood of receiving urate-lowering therapy (ULT), compared to Caucasians. There is an absence of strong data as to whether the response to ULT differs by race/ethnicity. BMC Musculoskeletal Disorders recently published a secondary analyses of the CONFIRMS trial, a large randomized controlled, double-blind trial of 2,269 gout patients. The authors reported that the likelihood of achieving the primary study efficacy end-point of achieving serum urate<6 mg/dl was similar between African-Americans and Caucasians, for all three treatment arms (Febuxostat 40 mg and 80 mg and allopurinol 300/200 mg). More importantly, rates were similar in subgroups of patients with mild or moderate renal insufficiency. Adverse event rates were similar, as were the rates of gout flares. These findings constitute a convincing evidence to pursue aggressive ULT in gout patients, regardless of race/ethnicity. This approach will likely help to narrow the documented racial disparities in gout care. Please see related article: http://www.biomedcentral.com/1471-2474/13/15.

Topics: Allopurinol; Black or African American; Female; Gout; Gout Suppressants; Humans; Male; Thiazoles

The need for comparative effectiveness (CE) data continues to grow, fuelled by market demand as well as health reform. There may be an assumption that new drugs result in improved efficacy compared with the standard of care, therefore warranting premium prices. Gout treatment has recently become controversial, as expensive new drugs enter the market with limited CE data.. The authors reviewed published clinical trials and conducted a cost effectiveness analysis on a new drug (febuxostat) versus the standard (allopurinol) to illustrate the limitations in using these data to inform evidence-based decision-making.. Although febuxostat trials included allopurinol as a comparator, methodological limitations make comparative effectiveness evaluations difficult. However, when available trial data were input to a decision analytic model, the authors found that a significant reduction in febuxostat cost would be required in order for it to dominate allopurinol in cost effectiveness analysis. This case exemplifies the challenges of using clinical trial data in comparative and cost effectiveness analyses.

Topics: Allopurinol; Clinical Trials as Topic; Comparative Effectiveness Research; Cost-Benefit Analysis; Decision Making; Decision Trees; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles

Xanthine oxidase (XO) is a complex metalloflavoprotein, overproduction of which usually leads to a pathological condition called Gout. XO inhibitors may prove to be promising antigout agents. Present investigation describes synthesis, characterization and evaluation of 26 thiazolo-pyrazolyl derivatives V(a-z) for XO inhibitory and free radical scavenging activities. Derivatives Vq, Vo and Vh showed most promising XO inhibitory and free radical scavenging activities on the basis of their IC(50) values ranging from (6.5-9 μM). Significant dock scores compared with Allopurinol have been figured out using molecular docking. Evaluation of Vq, Vo and Vh for both the activities for first time may provide a new approach for antigout research.

Topics: Allopurinol; Animals; Catalytic Domain; Drug Design; Enzyme Inhibitors; Free Radical Scavengers; Gout; Inhibitory Concentration 50; Models, Molecular; Pyrazoles; Rats; Thiazoles; Xanthine Oxidase

Gout is a painful inflammatory arthropathy caused by crystallization of monosodium urate within the joints. We present the case of a patient with primary gout who had positive results of joint aspiration and synovial biopsy for monosodium urate crystals in the third metacarpophalangeal joint but false-negative results of dual-energy computed tomography.

Topics: Allopurinol; Arthralgia; Biopsy; False Negative Reactions; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Male; Metacarpophalangeal Joint; Middle Aged; Predictive Value of Tests; Synovial Fluid; Tomography, X-Ray Computed; Uric Acid

Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Recombinant Fusion Proteins

Allopurinol is the most commonly used urate-lowering therapy in gout. Allopurinol hypersensitivity syndrome (AHS) is a rare but potentially fatal adverse event. Dosing guidelines based on creatinine clearance have been proposed based on the recognition that dosages of ≥300 mg/day may be associated with AHS, particularly in patients with renal impairment. However, the relationship between the allopurinol starting dose and AHS is unknown. This study was undertaken to determine the relationship between allopurinol dosing and AHS.. A retrospective case-control study of patients with gout who developed AHS between January 1998 and September 2010 was undertaken. For each case, 3 controls with gout who were receiving allopurinol but did not develop AHS were identified. Controls were matched with cases for sex, diuretic use at the time of initiating allopurinol, age (±10 years), and estimated glomerular filtration rate (estimated GFR). Starting dose and dose at the time of the reaction in cases were compared between cases and controls.. Fifty-four AHS cases and 157 controls were identified. There was an increase in the risk of AHS as the starting dose of allopurinol corrected for the estimated GFR increased. For the highest quintile of starting dose per estimated GFR, the odds ratio was 23.2 (P < 0.01). Receiver operating characteristic analysis indicated that 91% of AHS cases and 36% of controls received a starting dose of allopurinol of ≥1.5 mg per unit of estimated GFR (mg/ml/minute).. Our findings indicate that starting allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS. In patients who tolerate allopurinol, the dose can be gradually increased to achieve the target serum urate level.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; ROC Curve; Syndrome; Uric Acid

Urate lowering therapy in this country has mainly been achieved by the use of allopurinol and probenecid. A new xanthine oxidase inhibitor called febuxostat has been approved in 2009 for treatment of hyperuricaemia in gout. In this report, we describe the management of a patient with chronic tophaceous gout using febuxostat. The reduction in serum uric acid to target levels was rapid, and the tophi size had also reduced significantly while on therapy. There was no unwanted side effect observed during the therapy. Therefore, febuxostat would be a useful alternative drug in the treatment of hyperuricaemia in gout patients who have contraindications to allopurinol and probenecid.

Topics: Allopurinol; Chronic Disease; Contraindications; Febuxostat; Gout; Gout Suppressants; Humans; Male; Middle Aged; Probenecid; Thiazoles

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male

Topics: Allopurinol; Anti-Inflammatory Agents; Clinical Trials, Phase III as Topic; Drug Industry; Gout; Gout Suppressants; Humans; Uric Acid

The ability of antiinflammatory strategies to alter cardiovascular risk has not been rigorously examined. Colchicine is an antiinflammatory agent that affects macrophages, neutrophils, and endothelial cells, all of which are implicated in the pathogenesis of cardiovascular disease. We examined whether colchicine use was associated with a reduced risk of myocardial infarction (MI) in patients with gout.. We conducted a retrospective, cross-sectional study of all patients with an International Classification of Diseases, 9th ed, code for gout in the electronic medical record (EMR) of the New York Harbor Healthcare System Veterans Affairs network and ≥ 1 hospital visit between August 2007 and August 2008. Hospital pharmacy data were used to identify patients who had filled at least 1 colchicine prescription versus those who had not. Demographics and CV comorbidities were collected by EMR review. The primary outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and C-reactive protein (CRP) level.. In total, 1288 gout patients were identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users also had fewer deaths and lower CRP levels, although these did not achieve statistical significance. Colchicine effects persisted when allopurinol users were excluded from the analysis.. In this hypothesis-generating study, gout patients who took colchicine had a significantly lower prevalence of MI and exhibited trends toward reduced all-cause mortality and lower CRP level versus those who did not take colchicine.

Topics: Aged; Aged, 80 and over; Allopurinol; C-Reactive Protein; Colchicine; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Myocardial Infarction; New York; Prevalence; Retrospective Studies; Treatment Outcome; Uric Acid

Topics: Aged; Allopurinol; Biopsy; Cervical Vertebrae; Colchicine; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Hyperuricemia; Magnetic Resonance Imaging; Male; Neck Pain; Spinal Diseases; Tomography, X-Ray Computed; Treatment Outcome

We report the case of a man with chronic tophaceous gout who had end-stage renal failure secondary to the Alport syndrome. Following a failed kidney transplant, where urate deposition was a suspected contributor, the patient responded positively to consistent allopurinol therapy and regular haemodialysis sessions. Extensive and destructive tophi receded in size remarkably and the almost constant incidence of acute attacks of gout subsided. The patient has recently received a new kidney transplant and his plasma concentrations of urate are controlled well with allopurinol and he no longer experiences acute attacks of gout. While efficacious, adherence is critical for achieving the therapeutic effects of allopurinol even in end-stage renal disease.

Topics: Allopurinol; Follow-Up Studies; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

To estimate the degree of undercount of people diagnosed with gout in administrative datasets using capture-recapture methods.. Hospitalization and drug dispensing claims (allopurinol or colchicine) data for all Aotearoa New Zealand were used to estimate the prevalence of gout in 2009 (n = 4 295 296). As a comparison, we calculated gout prevalence using a large primary care dataset using general practitioner diagnosis and prescribing records (n = 555 313). For each of these datasets, we estimated the undercount through capture-recapture analysis using a Poisson regression model. A two-list model was used, which included covariates such as age, gender, ethnic groups and New Zealand deprivation quintiles.. The crude prevalence of diagnosed gout in the Aotearoa New Zealand population aged ≥ 20 years was 3.75%. The covariate-adjusted capture-recapture estimate of those not recorded but likely to have gout was 0.92%, giving an overall estimated prevalence of 4.67% (95% CI 4.49, 4.90%) for the population aged ≥ 20 years. This amounts to 80% of people with gout being identified by the algorithm for the Aotearoa New Zealand data-that is being recorded in either lists of dispensing of allopurinol or colchicine or hospital discharge. After capture-recapture, gout prevalence for all males aged ≥ 20 years was 7.3% and in older (≥ 65 years) Māori and Pacific men was >30%.. Capture-recapture analysis of administrative datasets provides a readily available method for estimating an aspect of unmet need in the population-in this instance potentially 20% of those with gout not being identified and treated specifically for this condition.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Colchicine; Databases, Factual; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Prevalence; White People

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Arthritis, Gouty; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Kidney Function Tests; Male; Middle Aged; Recurrence; Uric Acid

Gout care is suboptimal because of lack of translation of knowledge into real-world practice, despite evidence-based guidelines. We have developed processes to ensure systematic care for gout patients and determined the predictors for achievement of a target serum uric acid (SUA) concentration of < 360 μmol/L in a prospective cohort of Asian gout patients requiring allopurinol therapy.. A 1-year clinical practice improvement project was undertaken using evidence-based guidelines and quality planning tools. Interventions included comprehensive patient education, enhanced telephone access, reappointments and refills, upward titration of allopurinol with no limitation specified by renal function, and increased frequency of visits until the target SUA concentration was achieved. The primary outcome was the time to achieve an SUA level of <360 μmol/L.. We recruited 126 gout patients. The median time to achieving the target SUA concentration was 36.9 weeks [95% confidence interval (CI) 29.3-44.4]. Based on survival analysis, the proportion of patients achieving the target was 8.1% (95% CI 3.2-13.0), 40.6% (95% CI 31.4-50.8), and 72.0% (95% CI 61.2-82.8) at 3, 6, and 12 months, respectively. On average, our patients who achieved the target were seen once every 2 months and achieved the target after a mean of 2.5 (SD = 1.1) visits. Frequency of follow-up visits and older patients not taking aspirin were independent predictors associated with achieving the target outcome, regardless of renal function.. Optimization of control of SUA is achievable, even in the setting of renal impairment, by redesigning and implementing processes involving changes in physician prescribing habits, enhanced nursing interventions, and patient empowerment and education.

Topics: Adult; Aged; Allopurinol; Diet; Evidence-Based Medicine; Female; Gout; Gout Suppressants; Humans; Life Style; Male; Middle Aged; Patient Education as Topic; Practice Patterns, Physicians'; Prospective Studies; Quality Improvement; Self Care; Uric Acid

Gout is a chronic, potentially debilitating condition characterized by an inflammatory process in the joints or periarticular tissues that results from the deposition of monosodium urate crystals. Underdiagnosis and undertreatment can lead to the development of tophi and chronic arthropathy. A presumptive diagnosis of gout can be made on the basis of the clinical presentation as well as risk factors such as metabolic syndrome. Key conditions to rule out in the differential diagnosis are septic arthritis, calcium pyrophosphate deposition disease (pseudogout), fracture, and rheumatoid arthritis. Acute flares of gout should be managed with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids. With a diagnosis of gout, if urate-lowering therapy (ULT) is required, prophylaxis should be considered with low-dose colchicine or an NSAID, followed by the addition of ULT. The goal of ULT is to reach a serum uric acid (SUA) level ≤6.0 mg/dL. Measurements of SUA should be obtained after resolution of an acute attack, then periodically to facilitate titration of the ULT dose to achieve the target SUA level. Studies have confirmed significant reductions in gout attacks among patients who have attained SUA levels ≤6.0 mg/dL with ULT. Patient education concerning the disease and its treatment is essential to ensure close adherence with recommended therapies. Patients should also understand that ULT is intended as long-term, and for most patients, lifelong therapy to maximize the prospects for control of the disease. Clinicians should feel confident in making a presumptive diagnosis and choosing a therapeutic regimen for gout while effectively communicating with and educating patients about their disease.

Topics: Adrenal Cortex Hormones; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Long-Term Care; Medication Adherence; Referral and Consultation; Thiazoles; Uric Acid

Mangiferin, a natural bioactive xanthone C-glycoside, is widely present in medicinal plants like the leaf of Mangifera indica L. (Anacardiaceae). It has been reported that mangiferin possesses a variety of biological activities, including antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, and anticarcinogenic.. The hypouricemic effect and xanthine oxidoreductase (XOR) inhibitory activity of mangiferin were investigated here for the first time.. The hypouricemic effect of mangiferin was investigated in normal and hyperuricemic mice induced by potassium oxonate. Mangiferin at a dose of 0.75-100.0 mg/kg was given intragastrically to mice. The serum urate levels were determined using the phosphotungstic acid method. The hepatic activities of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in hyperuricemic mice were assayed using commercially available kits.. The results showed that mangiferin at a dose of 1.5, 3.0, and 6.0 mg/kg significantly reduced the serum urate levels (148.7 ± 37.8, 142.2 ± 44.5, 121.7 ± 21.7 µmmol/L) in hyperuricemic mice, compared with untreated hyperuricemic mice (201.8 ± 71.2 µmmol/L). However, mangiferin did not decrease the serum urate levels in normal mice until mangiferin was up to 100 mg/kg. In addition, the hepatic activities of XDH in hyperuricemic mice were significantly decreased by mangiferin, while no changes of XOD were observed. Acute toxicity study in mice showed that mangiferin was very safe at a dose of up to 25 g/kg.. These findings demonstrate that mangiferin has the potential to be developed as a new therapeutic agent for the treatment of hyperuricemia and gout.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Hyperuricemia; Liver; Male; Mice; Mice, Inbred Strains; Oxonic Acid; Time Factors; Toxicity Tests, Acute; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase; Xanthones

Hyperuricemia causes gouty arthritis, kidney disease, heart disease, and other diseases. Xanthine oxidase (XOD) and urate transporters play important roles in urate homeostasis. Numerous plants have been identified as XOD inhibitors. Longan seeds are known to contain high levels of polyphenols such as corilagin, gallic acid and ellagic acid. We examined the effect of longan seed extract on XOD inhibition and urate transporters GLUT1 and GLUT9 using both in vitro and in vivo assays. The results showed that dried longan seed extract (LSE) and its active components inhibited XOD dose-dependently in vitro. LSE inhibited uric acid production and XOD activity in normal liver cells (clone-9 cells) and was not cytotoxic under the concentration of 200 μg/ml. For the in vivo study, Sprague-Dawley (SD) rats were given intraperitoneally for thirty minutes with or without allopurinol (a XOD inhibitor, 3.5 mg/kg) or LSE (80 mg/kg) and then injected intraperitioneally with 250 mg/kg of oxonic acid and 300 mg/kg of hypoxanthine intragastrically. LSE was able to reduce serum uric acid level and XOD activity in hyperuricemic rats. However, LSE or allopurinol did not inhibit the liver XOD activities. On the other hand, GLUT1 protein was suppressed in kidney and GLUT9 was induced in liver from experimental rats and LSE or allopurinol decreased GLUT9 but increased GLUT1 protein level in the liver and kidney, respectively. These results confirmed the claimed effect of longan seeds on gout and other complications and suggested that its urate reducing effect might be due to modulation of urate transporters and inhibition of circulating xanthine oxidase.

Topics: Allopurinol; Animals; Glucose Transporter Type 1; Gout; Gout Suppressants; Hyperuricemia; Hypoxanthine; Kidney; Liver; Male; Monosaccharide Transport Proteins; Oxonic Acid; Phytotherapy; Plant Extracts; Polyphenols; Rats; Rats, Sprague-Dawley; Sapindaceae; Seeds; Uric Acid; Xanthine Oxidase

In the past few decades, the mouse has been used as a mammalian model for hyperuricemia and gout, which has increased not only in prevalence, but also in clinical complexity, accentuated in part by a dearth of novel advances in treatments for hyperuricemia and gouty arthritis. However, the use of mice for the development of gouty therapeutic drugs creates a number of problems. Thus, identification and evaluation of the therapeutic effects of chemicals in an alternative animal model is desirable. In the present study, the effects of gouty therapeutic drugs on lowering the content of uric acid and inhibiting activity of xanthine oxidase were evaluated by using a silkworm model, Bombyx mori L. (Lepidoptera: Bombycidae). The results showed that the effectiveness of oral administration of various gouty therapeutic drugs to 5(th) instar silkworms is consistent with results for human. The activity of xanthine oxidase of silkworm treated with allopurinol was lower, and declined in a dose-dependent manner compared with control silkworms, while sodium bicarbonate failed at inhibiting the activity of xanthine oxidase. The concentration of uric acid in the both hemolymph and fat body declined by 90 and 95% at six days post-administration with 25 mg/mL of allopurinol, respectively (p < 0.01), while the concentration of uric acid in both the hemolymph and fat body also declined by 81 and 95% at six days post-administration with 25 mg/mL of sodium bicarbonate, respectively (p < 0.01). Moreover, the epidermis of silkworm treated with allopurinol or sodium bicarbonate became transparent compared with the negative control group. These results suggest that silkworm larva can be used as an animal model for screening and evaluation of gouty therapeutic drugs.

Topics: Animals; Bombyx; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fat Body; Gout; Gout Suppressants; Hemolymph; Insect Proteins; Larva; Models, Animal; Uric Acid; Xanthine Oxidase

The aim of this study was to evaluate adherence to recommended serum uric acid levels in the rheumatology outpatients department of a university teaching hospital. We performed a retrospective study of all patients with a definitive diagnosis of gout attending our subspecialty gout clinic between 1 January 2010 and 31 December 2010. We evaluated adherence with two recently suggested uric acid thresholds, <300 μmol/L (<5 mg/dL) and <360 μmol/L (<6 mg/dL). Patient management was judged to adhere to the guidelines if either (1) the latest serum uric acid level was less than the specified guideline targets or (2) uric acid-lowering therapy was titrated upwards or the agent changed if the serum uric acid was above the guideline targets. One hundred two patients with a definitive diagnosis of gout attended the outpatients department between 1 January 2010 and 31 December 2010 and were included in the study. Median serum uric acid level was 331 μmol/L (IQR 276-456 μmol/L). Eighty-six patients (84 %) were treated with allopurinol, six patients (6 %) were treated with febuxostat (one of whom also received probenecid), and one with rasburicase. In 80 patients (78 %), the management adhered to a target guideline of <360 μmol/L (<6 mg/dL). In 66 patients (65 %), the management adhered to a target guideline of <300 μmol/L (<5 mg/dL). A treat-to-target approach has the potential to improve patient outcomes in the management of gouty arthritis. Our study shows encouraging results with the majority of patients on appropriate therapy and reaching recommended targets.

Topics: Aged; Allopurinol; Febuxostat; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Male; Middle Aged; Probenecid; Retrospective Studies; Thiazoles; Treatment Outcome; Uric Acid

Long term serum urate (SU) lowering to a target of <0.36 mmol/l (6 mg/dl) is recommended for effective gout management. However, many studies have reported low achievement of SU targets. The aim of this cross-sectional study was to examine the clinical and psychological factors associated with SU targets in patients with gout.. Patients with gout for <10 years were recruited from primary and secondary care settings. SU target was defined as SU concentration <0.36 mmol/L at the time of the study visit. Both clinical and psychological factors associated with SU target were analysed. The relationship between SU target and measures of gout activity such as flare frequency, tophi, work absences, and Health Assessment Questionnaire-II was also analysed.. Of the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36 mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose, patient confidence to keep SU under control, female sex, and ethnicity were independently associated with SU target. Other patient psychological measures and health-related behaviours, including adherence scores, were not independently associated with SU target in those taking ULT. Creatinine clearance, diuretic use, age, and body mass index were not associated with SU target. Patients at SU target reported lower gout flare frequency, compared with those not at target (p = 0.03).. ULT prescription and dosing are key modifiable factors associated with achieving SU target. These data support interventions focusing on improved use of ULT to optimise outcomes in patients with gout.

Topics: Adult; Aged; Allopurinol; Biomarkers; Cross-Sectional Studies; Down-Regulation; Drug Dosage Calculations; Female; Gout; Gout Suppressants; Health Knowledge, Attitudes, Practice; Humans; Logistic Models; Male; Medication Adherence; Middle Aged; Odds Ratio; Surveys and Questionnaires; Treatment Outcome; Uric Acid

Topics: Adult; Allopurinol; Colchicine; Elbow Joint; Finger Joint; Gout; Humans; Male; Patient Compliance; Severity of Illness Index; Tattooing

Gout is an inflammatory arthritis characterized by sudden, painful inflammation. Gout can affect any joint in an asymmetric distribution. Gouty attacks may be isolated or can be followed by years of recurrent flares. Over time, elevated serum urate levels and tophaceous deposits can lead to deformity and disability from underlying bony erosion. The concept of 'treatment-failure gout' describes a unique population that has been either unable to tolerate allopurinol or who have not experienced normalization of serum urate levels on allopurinol. It is estimated that approximately 1-1.5% of the estimated 3-8 million people with gout in the USA have treatment-failure gout. Pegloticase is an US FDA-approved intravenous medication that is a mammalian recombinant uricase conjugated to monomethoxy polyethylene glycol. Two recent Phase III trials have found pegloticase to be effective in the management of treatment-failure gout. These studies also highlight safety concerns regarding the drug's immunogenicity.

Topics: Allopurinol; Enzymes, Immobilized; Female; Gout; Gout Suppressants; Humans; Infusions, Intravenous; Male; Polyethylene Glycols; Randomized Controlled Trials as Topic; Treatment Failure; Treatment Outcome; Urate Oxidase; Uric Acid

Topics: Adult; Allopurinol; Colchicine; Gout; Gout Suppressants; Humans; Male; Panniculitis

Hyperuricemia and gout can be seen in patients with Paget's disease of bone (PD). This may be secondary to increased nucleic acid turnover in accelerated bone remodeling. It is unclear whether all PD patients should be evaluated for the presence of PD and gout in the same patient. In this report, I present a gout patient who later diagnosed as having PD and discuss the relationship between gout and PD.

Topics: Alendronate; Alkaline Phosphatase; Allopurinol; Biomarkers; Colchicine; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Osteitis Deformans; Patient Compliance

Topics: Adult; Allopurinol; Arthrography; Benzbromarone; Finger Joint; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Uricosuric Agents

Gouty panniculitis is an unusual clinical manifestation of gout, characterized by the deposition of monosodium urate crystals in the lobular hypodermis. Its pathogenesis is poorly understood but is associated with hyperuricemia, and the clinical presence of indurate subcutaneous plaques, which may precede or appear subsequently to the articular clinical expression of tophaceous gout. The aim of this report is to describe the clinical characteristics and potential risk factors for the development of lobular panniculitis secondary to chronic tophaceous gout. This is a retrospective clinical review of 6 patients with gouty panniculitis seen at the rheumatology service at the National University of Colombia. All cases fulfill diagnostic criteria for gout. The presenting clinical characteristics of each case were analyzed. All 6 patients were men, with an average age of 26 years. Two patients initially presented with cutaneous manifestations, and in the remainder 4 joint involvements preceded the cutaneous manifestations. Articular involvement first developed in lower extremities, of intermittent nature, and subsequent occurrence of polyarthritis of upper and lower extremities. A positive family history of gout was observed in half of the patients. Smoking and high alcohol intake were relevant risk factors. On physical examination, all exhibited the presence of erythematous, irregular surface, deep indurate subcutaneous plaques. Biopsy of skin and deep dermis including panniculus revealed the presence of granulomatous inflammatory changes with deposition of amorphous eosinophilic material surrounded by palisading histocytes and lymphocytes. Characteristic negative birefringent monosodium urate crystals were observed in the synovial fluid of patients with arthritis. All patients exhibited high levels of serum uric acid and were non-complaint to treatment with allopurinol, NSAIDs, and colchicine. Gouty panniculitis should be considered in the differential diagnosis of panniculitis, especially in the presence of high levels of uric acid. It is usually observed in the third decade of life and may appear prior to the inflammatory articular manifestations of tophaceous gout.

Topics: Adult; Allopurinol; Colchicine; Crystallization; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Microscopy, Polarization; Middle Aged; Panniculitis; Retrospective Studies; Synovial Fluid; Uric Acid

Topics: Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Biopsy; Gout; Gout Suppressants; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Pain Measurement; Radiography; Treatment Outcome

In Mediterranean folk medicine Olea europaea L. leaf (Ph.Eur.) preparations are used as a common remedy for gout. In this in vitro study kinetic measurements were performed on both an 80% ethanolic (v/v) Olea europaea leaf dry extract (OLE) as well as on nine of its typical phenolic constituents in order to investigate its possible inhibitory effects on xanthine oxidase (XO), an enzyme well known to contribute significantly to this pathological process. Dixon and Lineweaver-Burk plot analysis were used to determine K(i) values and the inhibition mode for the isolated phenolics, which were analysed by RP-HPLC for standardisation of OLE. The standardised OLE as well as some of the tested phenolics significantly inhibited the activity of XO. Among these, the flavone aglycone apigenin exhibited by far the strongest effect on XO with a K(i) value of 0.52 μM. In comparison, the known synthetic XO inhibitor allopurinol, used as a reference standard, showed a K(i) of 7.3 μM. Although the phenolic secoiridoid oleuropein, the main ingredient of the extract (24.8%), had a considerable higher K(i) value of 53.0 μM, it still displayed a significant inhibition of XO. Furthermore, caffeic acid (K(i) of 11.5 μM; 1.89% of the extract), luteolin-7-O-β-D-glucoside (K(i) of 15.0 μM; 0.86%) and luteolin (K(i) of 2.9 μM; 0.086%) also contributed significantly to the XO inhibiting effect of OLE. For oleuropein, a competitive mode of inhibition was found, while all other active substances displayed a mixed mode of inhibition. Tyrosol, hydroxytyrosol, verbascoside, and apigenin-7-O-β-D-glucoside, which makes up for 0.3% of the extract, were inactive in all tested concentrations. Regarding the pharmacological in vitro effect of apigenin-7-O-β-D-glucoside, it has to be considered that it is transformed into the active apigenin aglycone in the mammalian body, thus also contributing substantially to the anti-gout activity of olive leaves. For the first time, this study provides a rational basis for the traditional use of olive leaves against gout in Mediterranean folk medicine.

Topics: Allopurinol; Animals; Apigenin; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gout; Iridoid Glucosides; Iridoids; Medicine, Traditional; Olea; Phenols; Plant Extracts; Plant Leaves; Plants, Medicinal; Pyrans; Uric Acid; Xanthine Oxidase

Gout is commonly undertreated and can lead to significant disability. Few data are available about the lived experience of gout or the barriers to effective urate-lowering therapy in men with gout.. This study aims to understand the experience of men living with chronic gout using a qualitative grounded theory approach.. Eleven English-speaking men with chronic gout participated in an in-depth semistructured interview about their experiences of living with gout. Interviews were recorded and transcribed. Consensus groups were used to analyze and validate the themes arising from the transcripts.. Three major themes related to the experience of gout emerged from the interviews: the impact of disease (pain, dependency on family members during flares, isolation, work disability), the progressiveness of untreated gout (increasing number of affected joints and frequency of flares, increase in food type triggers, escalating treatment required to control flares due to reducing efficacy of anti-inflammatory medication), and the lack of knowledge of gout (a community wide lack of understanding of the causes or prevention of gout, stoicism/tolerance to symptoms and disability, personal and social stigma related to gout).. Chronic gout has an important impact on both the patient and his family. This work provides previously hidden perspectives of the experience of gout, which may be generalized to other men with gout, suggesting that shame, embarrassment, and stigma lead to trivialization of the impact of disease despite its severity. These experiences may lead to undertreatment of gout because of lack of disclosure of symptom severity and lack of expectation of treatment effectiveness, which in turn could contribute to the development of progressive gout.

Topics: Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Attitude to Health; Chronic Disease; Diet; Disease Progression; Exercise; Female; Gout; Gout Suppressants; Health Status; Humans; Male; Middle Aged; Pain Measurement; Qualitative Research; Quality of Life; Social Support

So far, few data are available to characterize the flare history of patients with gout. The objective of this study was to describe the frequency and risk factors of gout flares with special consideration of the comorbidity.. A cohort study was conducted in a U.K. general practice database (The Health Improvement Network) including all patients aged 20-89 years diagnosed with incident gout between the years 2000 and 2007.. In this study, 23 857 incident gout patients (mean age 61.9 years) were included, overall incidence rate was 2.68 (95% CI 2.65, 2.72) per 1000 person-years. The proportion of patients with at least one flare during the follow-up period (mean 3.8 years) was 36.9% (n=8806). A history of ischaemic heart disease [hazard ratio (HR) 1.12 (95% CI 1.06, 1.19)], hypertension [HR 1.15 (95% CI 1.10, 1.20)] and renal failure [HR 1.33 (95% CI 1.20, 1.48)] were independently associated with a higher risk of a first gout flare. Use of allopurinol at initial gout diagnosis was associated with a lower risk [HR 0.80 (95% CI 0.75, 0.85)].. Gout flares are relatively common among patients with gout. Some of the underlying cardiometabolic comorbid conditions are themselves independent risk factors for flares, which further contribute to the complexity of treatment of gout flares.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Comorbidity; Female; General Practice; Gout; Gout Suppressants; Humans; Hypertension; Incidence; Male; Middle Aged; Obesity; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; United Kingdom

Topics: Aged; Allopurinol; Australia; Colchicine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Febuxostat; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Kidney Diseases; Male; Patient Compliance; Practice Guidelines as Topic; Prednisolone; Renal Dialysis; Thiazoles; Uric Acid

Allopurinol is used to lower serum uric acid (sUA) levels in gout patients. The objective of this study was to investigate the influence of physician specialty on allopurinol treatment patterns and sUA control.. This was a retrospective study using claims from a managed care database of US health plan enrollees. Gout patients at least 18 years of age who received allopurinol were identified from the database between January 1, 2002 and April 30, 2007. The index date was defined as the date of the earliest allopurinol claim, and patients were required to have health plan enrollment for at least 365 days prior to and following the index date for inclusion. Physician specialty was determined using the index allopurinol claim. Dosage of allopurinol prescription(s) and number of gout flares were determined from claims data. sUA measurements were used to assess goal attainment over a period of at least one year following the index allopurinol prescription.. There were 3363 patients with gout of whom 69.9% received an index allopurinol prescription from a generalist/internist, 5.7% from a rheumatologist, 2.6% from a nephrologist, and 21.8% from a physician with other specialty. Of patients receiving their index prescription from a nephrologist, 38.7% reached the sUA goal of <6 mg/dL (357 μmol/L), as compared to patients prescribed by a rheumatologist, generalist/internist, or other physician (35.4%, 31.4%, and 39.4%, respectively; P = 0.015). When controlling for patient characteristics, multivariate analysis did not reveal statistically significant different odds of sUA goal attainment based on prescribing physician specialty, though separate analyses indicated that patients prescribed by a nephrologist had fewer gout flares. Change in allopurinol dosage from initial to final dose was more frequent among patients prescribed by rheumatologists and nephrologists.. There is significant heterogeneity in the specialists' management of sUA levels in patients with gout, possibly reflecting differences in case mix and treatment approaches. Limitations related to the use of claims data, such as inability to observe medications filled over-the-counter, should be considered when interpreting study results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Managed Care Programs; Medicine; Middle Aged; Physicians; Practice Patterns, Physicians'; Registries; Retrospective Studies; Young Adult

Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied.. A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease.. The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III).. Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.

Topics: Aged; Aged, 80 and over; Allopurinol; Colchicine; Comorbidity; Contraindications; Diabetes Mellitus; Drug Prescriptions; Female; Gastroesophageal Reflux; Glucocorticoids; Gout; Gout Suppressants; Hepatitis, Chronic; Humans; Hypertension; Male; Middle Aged; Prevalence; Probenecid; Renal Insufficiency, Chronic; Severity of Illness Index; Uricosuric Agents

To characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes.. A cohort study using a record-linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined.. Six thousand and forty-two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl(-1) . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non-ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95-1.26] and the non-ULT group with urate >6 mg dl(-1) (adjusted HR 1.07, 95% CI 0.89-1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9-86.1) per 1000 person years for the 100 mg group, 69.7 (49.6-89.8) for the 200 mg group and 47.6 (38.4-56.9) for the ≥300 mg group. Compared with low-dose (100 mg) users, high-dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50-0.94) and mortality (adjusted HR 0.75, 95% CI 0.59-0.94).. Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality.

Topics: Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Cohort Studies; Female; Gout; Gout Suppressants; Hospitalization; Humans; Hyperuricemia; Male; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome; United Kingdom; Uric Acid

Topics: Allopurinol; Antihypertensive Agents; Gout; Gout Suppressants; Humans; Hydrochlorothiazide; Hypertension; Uric Acid

Allopurinol has been a standard hypouricemic agent for more than 40 years, but febuxostat, which is also a xanthine oxidase inhibitor, is now available. We present a case of tophaceous gout with uric acid levels that did not respond to prescription of very high doses of allopurinol or uricosuric agents. With febuxostat treatment, the patient had rapid and sustained reduction in her uric acid levels to target range. This case raises the possibility of currently unrecognized pharmacologic differences between allopurinol and febuxostat.

Topics: Allopurinol; Dose-Response Relationship, Drug; Drug Resistance; Febuxostat; Female; Gout; Gout Suppressants; Humans; Thiazoles; Treatment Failure; Treatment Outcome; Uric Acid; Young Adult

Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO) activity, remains the standard for pharmacologic urate-lowering management of gout. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol adverse reactions (AE) occur much less frequently, and include severe cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol hypersensitivity syndrome. During clinical development of febuxostat (FEB), a recently approved non-purine analog inhibitor of XO, subjects with severe allopurinol intolerance were excluded from randomized double-blind FEB/allopurinol comparative trials.. In this retrospective study, safety and urate-lowering efficacy of FEB was assessed in 13 successively encountered gout patients with prior documented severe allopurinol reactions.. FEB was well tolerated in 12 of 13 patients, each of whom remains on treatment. One patient previously hospitalized with documented exfoliative erythroderma during allopurinol treatment, developed biopsy-confirmed cutaneous leukocytoclastic vasculitis. None of the other 12 patients treated with FEB showed rash, worsening hepatic function, blood cytopenia or eosinophilia.. In 12 of our 13 gout patients with previously documented severe allopurinol AE, FEB treatment was safe. However, the development of a hypersensitivity type cutaneous vasculitis (likely but not definitively FEB-related) early in treatment mandates caution, careful dose escalation, and close monitoring when FEB urate-lowering therapy of allopurinol-intolerant patients is considered.

Topics: Aged; Aged, 80 and over; Allopurinol; Drug Monitoring; Febuxostat; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Thiazoles; Uric Acid

Topics: Acute Disease; Adult; Allopurinol; Cervical Vertebrae; Gout; Gout Suppressants; Humans; Laminectomy; Magnetic Resonance Imaging; Male; Paraplegia; Radiography; Spinal Cord Diseases; Treatment Outcome

The treatment of gout requires a lowering of serum urate (SU) levels, and allopurinol is the drug that is most commonly used for this purpose. The objectives of this study were to define the relationships between allopurinol dose on the one hand and plasma oxypurinol, renal function, and SU levels on the other and to determine the minimum plasma oxypurinol concentration that would result in a target level of <6 mg/dl (0.36 mmol/l) of SU. For this purpose, 82 patients who had been receiving allopurinol for at least 1 month were recruited. Patients with SU <6 mg/dl were followed up quarterly for 12 months. In patients with SU ≥6 mg/dl, the dose of allopurinol was increased to bring the level of SU to <6 mg/dl. These patients were followed up once a month until the SU level remained at <6 mg/dl for 3 consecutive months; thereafter they were seen quarterly. SU, creatinine, and plasma oxypurinol were measured 6-9 hours after administration of the allopurinol dose. There were significant inverse correlations between creatinine clearance (CrCl) and plasma oxypurinol (P = 0.002), between allopurinol dose and SU (P < 0.0001) and between plasma oxypurinol and SU (P < 0.0001). Using receiver operating characteristic analysis, the target SU of <6 mg/dl was achieved in 75% of serum samples with plasma oxypurinol levels of >100 µmol/l (15.2 mg/l). Increasing the allopurinol dose resulted in increased plasma oxypurinol and reduced SU concentrations. Plasma oxypurinol concentrations >100 µmol/l were required to achieve SU <6 mg/dl.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Arthritis, Gouty; Chronic Disease; Creatinine; Dose-Response Relationship, Drug; Drug Monitoring; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Humans; Kidney Function Tests; Male; Middle Aged; Oxypurinol; Standard of Care; Uric Acid

To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout.. This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg.. A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD.. About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

Topics: Adult; Aged; Allopurinol; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Kidney Failure, Chronic; Male; Managed Care Programs; Middle Aged; Retrospective Studies; Uric Acid

Since the discovery of the inflammasome, interleukin 1 production has been found to be integral in the pathophysiology of gout. Interleukin 1 inhibition by Anakinra has been shown to effective for the treatment of gout. We report three cases of resistant chronic tophaceous gout who responded to anakinra subcutaneous injections on an intermittent basis.

Topics: Acute Disease; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colchicine; Drug Resistance; Gout; Gout Suppressants; Humans; Injections, Subcutaneous; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Male; Middle Aged; Treatment Outcome

Topics: Acute Disease; Aged; Allopurinol; Antibodies, Monoclonal; Drug Resistance; Fatal Outcome; Gout; Gout Suppressants; Humans; Infliximab; Male; Treatment Outcome; Tumor Necrosis Factor-alpha; Urate Oxidase

Topics: Adolescent; Adult; Allopurinol; Animals; Antihypertensive Agents; Child; Disease Models, Animal; Evidence-Based Medicine; Gout; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Practice Guidelines as Topic

Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid (SUA) of <6 mg/dl, remains the standard of care for the chronic management of gout. New urate-lowering medications are important options; however, these agents should be reserved for patients who do not tolerate or cannot achieve SUA <6 mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol therapy suggests that allopurinol should still be considered first-line ULT for gout.

Topics: Allopurinol; Arthritis, Gouty; Enzyme Inhibitors; Female; Gout; Gout Suppressants; Humans; Male; Oxypurinol; Uric Acid

To identify factors associated with acute gout attacks in normouricaemic gout patients receiving allopurinol.. We reviewed the medical records of 860 patients with chronic gout who were treated with allopurinol at a single tertiary hospital between 2003 and 2009. Of these, 135 patients had serum urate concentrations ≤ 360 μmol/L (6 mg/dL). Patients whose serum urate concentrations exceeded 360 μmol/L (6 mg/dL) at least once during follow-up were excluded. Patients who experienced at least one acute attack during follow-up, despite normouricaemia [≤ 360 μmol/L (6 mg/dL)], were classified as the Attack group (n = 51). The others were classified as the Non-attack group (n = 84).. The gout disease duration was significantly longer in the Attack group than in the Non-attack group (p = 0.036). The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients. Multivariate analysis showed that both the presence of tophi [odds ratio (OR) 4.16, 95% confidence interval (CI) 1.41-12.23, p = 0.010] and the number of involved joints (OR 1.51, 95% CI 1.05-2.17, p = 0.028) were independently associated with acute attacks in normouricaemic gout patients receiving allopurinol.. The presence of tophi and multiple joint involvement were associated with acute attacks in normouricaemic gout patients receiving allopurinol.

Topics: Acute Disease; Aged; Allopurinol; Arthritis, Gouty; Gout; Gout Suppressants; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Uric Acid

Topics: Acute Disease; Aged; Allopurinol; Colchicine; Cytokines; Female; Gout; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Steroids; Transplantation, Homologous

Gout is increasing in prevalence throughout the world, particularly in developed countries. The causes are dietary--purine-rich foods, high saturated fats, fructose-containing drinks and alcohol. Gout is also drug-related and associated with increased obesity, hypertension, insulin resistance and metabolic syndrome. Although very readily treated, there is evidence that physicians fail to optimise the treatment and achieve low enough serum urate levels, while patients fail to comply with the treatment and dietary advice. Standard treatment of acute attacks is with non-steroidal anti-inflammatory drugs, colchicine or steroids. The standard urate-lowering agents are allopurinol and uricosuric agents. Newer urate lowering agents are now available for refractory gout. Increased understanding of the membrane transporters involved in urate excretion in the kidney and the genes that control them and of the way that sodium urate crystals cause inflammation via the innate immune system and the inflammasome offers hope for new therapeutic approaches.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Diet; Gout; Gout Suppressants; Humans; Hyperuricemia; Immunity, Innate; Inflammation; Kidney; Membrane Transport Proteins; Standard of Care; Steroids; Uric Acid

Topics: Allopurinol; Colchicine; Comorbidity; Drug Interactions; Gout; Gout Suppressants; Humans; New Zealand; Practice Patterns, Physicians'

Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Child; Erythema Multiforme; Female; Genetic Association Studies; Genetic Testing; Genetic Variation; Gout; Gout Suppressants; HLA Antigens; Humans; Hyperuricemia; Male; Middle Aged; Pharmacogenetics; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome

Topics: Allopurinol; Chronic Disease; Drug Discovery; Drug Utilization; Gout; Gout Suppressants; Guideline Adherence; Humans; Practice Guidelines as Topic; Practice Patterns, Physicians'; Probenecid

Topics: Allopurinol; Dose-Response Relationship, Drug; Gout; Gout Suppressants; Humans; Kidney

This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of <6 mg/dl. In two patients, SU levels remained above 6 mg/dl (treated with allopurinol, n = 1; treated with colchicine, n = 1). At baseline, the double contour sign was seen in all patients. In those patients who achieved SU levels of <6 ml/dl, this sign had disappeared at follow-up. Disappearance of the double contour sign was seen in two knee joints, two first MTP joints, and one MCP joint. In contrast, disappearance of the double contour sign was not seen in patients who maintained a SU level > or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain < or =6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.

Topics: Aged; Aged, 80 and over; Allopurinol; Cartilage, Articular; Colchicine; Crystallization; Female; Gout; Gout Suppressants; Humans; Hyaline Cartilage; Joints; Male; Middle Aged; Probenecid; Treatment Outcome; Ultrasonography; Uric Acid

An unusual picture of polyarticular tophaceous gout is reported. It concerns a 61-year-old patient with tophaceous deposits for 30 years. Descriptive clinical and radiographic images are furnished.

Topics: Allopurinol; Arthrography; Calcium Channel Blockers; Chronic Disease; Disease Progression; Elbow; Elbow Joint; Foot; Foot Deformities; Gout; Gout Suppressants; Hand; Humans; Joints; Magnetic Resonance Imaging; Male; Metacarpophalangeal Joint; Middle Aged; Patient Compliance; Sulfonamides

Xanthine oxidase is a flavoprotein enzyme which catalyzes the oxidative hydroxylation of purine substrates. Because of its availability, it has become a model for structural molybdoenzymes in general. The enzyme is a well-established target of drugs against gout and hyperuricemia and exists in two forms: oxidase and deshydrogenase. In some pathologies, its level increases in oxidase form, being the source of free radicals which can cause damage to surrounding tissues. It is important to understand the mechanisms of the enzyme inhibition to help in the search of new inhibitors. The main active center is a molybdopterin buried in a cavity. Theoretical calculations can be of some help for distinguishing the important aspects in the inhibition: attraction inside the cavity and anchorage. In this paper, the molybdopterin molecule geometry has been optimized by ab initio with the DFT method and the results have been shown to be very similar to the X-ray coordinates. In order to evaluate the attraction inside the cavity, the electrostatic potential between the charged molybdopterin molecule and two series of inhibitors, some flavonoids, and some gallic acid derivatives have been calculated using the multipolar development supplied by the Gaussian package. The good concordance between the electrostatic force and IC(50) indicates that the attraction is an important factor in the inhibition and must be taken into account in the designing of new drugs.

Topics: Animals; Catalytic Domain; Cattle; Flavonoids; Gallic Acid; Gout; Humans; Hyperuricemia; Models, Molecular; Molecular Conformation; Xanthine Oxidase

Serum creatinine level is the most commonly used indices for assessment of glomerular filtration rate (GFR), even though these indices have been shown to have some limitations in clinical practice. We investigated the diagnostic efficacy of serum cystatin C compared to that of serum creatinine levels and identified the relating factors associated with changes in serum cystatin C levels in gout patients with renal impairment. A total of 68 gouty patients with renal impairment were enrolled in this study. Diagnostic efficacy of serum cystatin C levels was evaluated through non-parametric receiver operating characteristic (ROC) analysis. The risk factors for changes in serum cystatin C levels were confirmed using multivariate regression analysis. With 24-hr urine creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702, P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the clinical parameters for increased serum cystatin C are a higher stage of chronic kidney disease, older age, use of allopurinol, and lower high density lipoprotein-cholesterol. The area under the curve (AUC) at ROC plots identified that of serum cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C is a reliable endogenous marker for the assessment of renal function or GFR in gout patients with renal impairment.

Topics: Age Factors; Aged; Allopurinol; Area Under Curve; Biomarkers; Cholesterol, HDL; Creatinine; Cystatin C; Glomerular Filtration Rate; Gout; Gout Suppressants; Humans; Male; Middle Aged; Renal Insufficiency; Risk Factors; ROC Curve

To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy.. From 2 integrated delivery systems, we identified patients 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of 1 prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy.. There were 4166 new users of urate-lowering drugs (97% received allopurinol), of whom 2929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45-74 years (<45 referent) and greater duration of urate-lowering drug use before the gap was associated with resuming treatment within 1 year. In contrast, receipt of nonsteroidal anti-inflammatory drugs or glucocorticoids in the year before the gap was associated with a reduced likelihood of resuming therapy.. The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions, given the clinical consequences of nonadherence.

Topics: Age Factors; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; Chronic Disease; Cohort Studies; Colchicine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glucocorticoids; Gout; Gout Suppressants; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Compliance; Probability; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Sex Factors; Time Factors; Treatment Outcome; Uric Acid

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Female; Gout; Gout Suppressants; Hand Joints; Humans; Radiography; Toe Joint

Simiao pill is one of the most frequently prescription in traditional Chinese medicine to treat gout and hyperuricemia.. We investigated the effects of Simiao pill on urate excretion and renal function and examined whether renal organic ion transporters are involved in potassium oxonate-induced hyperuricemic mice.. Water extract of Simiao pill at 507, 1014 and 2028mg/kg was orally administered to hyperuricemic and normal mice for 7 days, and allopurinol (5mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic and normal mice treated with Simiao pill and allopurinol. Simultaneously, the mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9) and organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in the kidney were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.. Simiao pill significantly reduced serum uric acid levels and increased FEUA dose-dependently in hyperuricemic mice. And it effectively reversed oxonate-induced alterations in renal mURAT1, mGLUT9 and mOAT1 mRNA and protein levels, resulting in the enhancement of renal urate excretion in mice. Moreover, Simiao pill decreased serum creatinine levels, as well as increased renal mOCT1, mOCT2, mOCTN1 and mOCTN2 mRNA and protein levels, leading to improve renal dysfunction in this model.. These findings suggest that Simiao pill processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic animals.

Topics: Allopurinol; Animals; Biological Transport; Gout; Hyperuricemia; Kidney; Male; Mice; Mice, Inbred Strains; Organic Anion Transporters; Oxonic Acid; Reverse Transcriptase Polymerase Chain Reaction; Uric Acid

Why chronic gout, that is mostly a well diagnosed and controlled disease if it is timely and systematically treated with allopurinol, becomes a topical public health problem following 50 years after the introduction of pathogenetic therapy with xantine oxidase inhibitors is under consideration. The principles of rational therapy for chronic gouty arthritis are outlined.

Topics: Allopurinol; Chronic Disease; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Xanthine Oxidase

The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

Topics: Aged; Allopurinol; Diagnosis, Differential; Drug Hypersensitivity; Fatal Outcome; Gout; Humans; Kidney Failure, Chronic; Male; Multiple Organ Failure; Recurrence; Stevens-Johnson Syndrome

Topics: Allopurinol; Drug Hypersensitivity; General Practice; Gout; Gout Suppressants; Guideline Adherence; Humans; Practice Patterns, Physicians'; Risk Factors; Time Factors; Treatment Failure; Uric Acid

Topics: Allopurinol; Drug Hypersensitivity; Gastritis; Gout; Gout Suppressants; Humans; Male; Middle Aged; Probenecid; Uric Acid; Uricosuric Agents

To find factors associated with the development of renal colic during uricosuric therapy.. We performed a prospective cohort followup study of patients with gout and no previous history of kidney stones who had been treated with uricosurics. Clearance of creatinine and urate, 24-hour urinary uric acid (UA), undissociated urinary UA concentration, 24-hour undissociated urinary UA, and pH and urine sediment were obtained. Cox proportional hazards regression analysis was used to identify variables associated with renal colic as the outcome. The rate of renal colic was compared with that of control patients receiving allopurinol who had no previous history of renal stones.. We analyzed a 784 patient-year exposure from 216 patients: 206 with renal underexcretion of UA and 10 with normal excretion. There were 21 clinical events. Two variables showed increased risk hazard for developing lithiasis: clearance of UA at baseline and undissociated urinary UA concentration during followup. When only patients with underexcretion of UA were included in the analysis, undissociated urinary UA during followup remained the only statistically significant variable. Patients who showed an undissociated UA concentration < 20 mg/dl did not show an increase in the rate of lithiasis or events compared with patients receiving allopurinol.. Clearance of UA at baseline may be useful for selecting patients suitable for uricosuric treatment. The estimation of the concentration of undissociated urinary UA is useful for evaluating the risk of lithiasis during followup.

Topics: Allopurinol; Benzbromarone; Cohort Studies; Creatinine; Follow-Up Studies; Gout; Humans; Hyperuricemia; Middle Aged; Proportional Hazards Models; Prospective Studies; Renal Colic; Risk Factors; Time Factors; Uric Acid; Uricosuric Agents; Urolithiasis

In order to further understand and assess the validity of herbal medicine, we investigated the potential inhibitory effect of various extracts from Fraxinus angustifolia and Pistacia lentiscus, two plants used traditionally in Algeria against several inflammatory diseases such as rheumatism, arthritis, and gout, on purified bovine milk xanthine oxidase (XO) activity. The total phenolic contents of the leaves and bark of F. angustifolia and the leaves and seeds of P. lentiscus were estimated. P. lentiscus aqueous fractions from hexane and chloroform extractions and F. angustifolia aqueous fraction from ethyl acetate extraction inhibited XO activity by 72.74 +/- 2.63% (50% inhibitory concentration [IC(50)] = 27.52 microg/mL), 68.97 +/- 3.89% (IC(50) = 42.46 microg/mL) and 53.92 +/- 3.17% (IC(50) = 58.84 mmicroug/mL), respectively, at 100 microg/mL, compared to that of reference drug, allopurinol (98.18% [IC(50) = 6.34 microg/mL]). Moreover, at a concentration of 50 microg/mL, both P. lentiscus extracts showed inhibition rates higher than 50%. F. angustifolia leaf extracts showed only mild inhibition. Lineweaver-Burk analysis showed that the inhibitory activity exerted by F. angustifolia bark aqueous extract and P. lentiscus aqueous extracts is of mixed type, whereas the leaf extracts from F. angustifolia inhibited XO noncompetitively. Positive correlations were established between XO inhibition and total phenols (r = 0.89) and flavonoids (r = 0.93) for P. lentiscus and with total phenols (r = 0.72) and tannins (r = 0.54) for F. angustifolia. Our findings suggest that the therapeutic use of these plants may be due to the observed XO inhibition, thereby supporting their use in traditional folk medicine against inflammatory-related diseases, in particular, gout.

Topics: Algeria; Animals; Arthritis, Rheumatoid; Cattle; Down-Regulation; Enzyme Inhibitors; Fraxinus; Gout; Humans; Kinetics; Milk; Pistacia; Plant Extracts; Xanthine Oxidase

Topics: Aged; Allopurinol; Back Pain; Biopsy, Needle; Gout; Gout Suppressants; Humans; Injections, Epidural; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Sacrum; Spinal Diseases; Steroids; Treatment Outcome

Hyperuricemia is associated with reduced survival among patients with heart failure (HF), but the effect of gout on HF outcomes is unknown. A recent randomized trial suggested that allopurinol may reduce adverse outcomes among patients with hyperuricemia and HF. Our objective was to determine whether gout and allopurinol use are associated with HF outcomes.. Time-matched, nested case-control analysis of a retrospective cohort of patients with HF who were 66 years or older using health care databases in Quebec, Canada. The primary outcome measure was a composite measure of HF readmission and all-cause mortality. The secondary outcome measure was all-cause mortality. Rate ratios were calculated using conditional logistic regression and adjusted for known prognostic factors.. Of the 25,090 patients in this cohort, 14,327 experienced the primary outcome. Both a remote history of gout and an acute episode of gout (within 60 days of the event date) were associated with an increased risk of HF readmission or death (adjusted rate ratio, 1.63; 95% confidence interval, 1.48-1.80; P<.001 and 2.06; 1.39-3.06; P<.001, respectively). Continuous allopurinol use (>30 days of continuous use) was not associated with the primary outcome among the overall population with HF (adjusted rate ratio, 1.02; 95% confidence interval, 0.95-1.10; P=.55) but was associated with reduced HF readmissions or death (0.69; 0.60-0.79; P<.001) and all-cause mortality (0.74; 0.61-0.90; P<.001) among patients with a history of gout.. Patients with HF and a history of gout represent a high-risk population. Among such patients, the use of allopurinol is associated with improved outcomes.

Topics: Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Female; Gout; Gout Suppressants; Heart Failure; Humans; Male; Patient Readmission; Quebec; Retrospective Studies; Treatment Outcome

Oxypurinol is the active metabolite of allopurinol which is used to treat hyperuricaemia associated with gout. Both oxypurinol and allopurinol inhibit xanthine oxidase which forms uric acid from xanthine and hypoxanthine. Plasma oxypurinol concentrations vary substantially between individuals and the source of this variability remains unclear. The aim of this study was to develop an HPLC-tandem mass spectrometry method to measure oxypurinol in urine to facilitate the study of the renal elimination of oxypurinol in patients with gout. Urine samples (50 microL) were prepared by dilution with a solution of acetonitrile/methanol/water (95/2/3, v/v; 2 mL) that contained the internal standard (8-methylxanthine; 1.5 mg/L), followed by centrifugation. An aliquot (2 microL) was injected. Chromatography was performed on an Atlantis HILIC Silica column (3 microm, 100 mm x 2.1mm, Waters) at 30 degrees C, using a mobile phase comprised of acetonitrile/methanol/50 mM ammonium acetate in 0.2% formic acid (95/2/3, v/v). Using a flow rate of 0.35 mL/min, the analysis time was 6.0 min. Mass spectrometric detection was by selected reactant monitoring (oxypurinol: m/z 150.8-->108.0; internal standard: m/z 164.9-->121.8) in negative electrospray ionization mode. Calibration curves were prepared in drug-free urine across the range 10-200 mg/L and fitted using quadratic regression with a weighting factor of 1/x (r(2) > 0.997, n=7). Quality control samples (20, 80, 150 and 300 mg/L) were used to determine intra-day (n=5) and inter-day (n=7) accuracy and imprecision. The inter-day accuracy and imprecision was 96.1-104% and <11.2%, respectively. Urinary oxypurinol samples were stable when subjected to 3 freeze-thaw cycles and when stored at room temperature for up to 6h. Samples collected from 10 patients, not receiving allopurinol therapy, were screened and showed no significant interferences. The method was suitable for the quantification of oxypurinol in the urine of patients (n=34) participating in a clinical trial to optimize therapy of gout with allopurinol.

Topics: Allopurinol; Chromatography, High Pressure Liquid; Drug Stability; Gout; Humans; Hyperuricemia; Oxypurinol; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Xanthines

To compare characteristics of gout in Hmong patients versus whites, and examine if Hmong ethnicity is associated with risk of tophaceous gout.. A retrospective chart review of Hmong and White patients with gout in a large health care system (Health Partners) in St. Paul, Minnesota, from January 2001 to March 2008, to compare clinical characteristics and risk factors for gout. Multivariable-adjusted hierarchical logistic regressions examined the association of Hmong ethnicity with risk of tophaceous gout, adjusting for age, sex, hypertension, diuretic use, and kidney function.. The analytic dataset consisted of 89 Hmong patients and 84 White controls, all of whom had ethnicity confirmed, an International Classification of Diseases, ninth revision code for gout and had at least 2 physician-documented diagnoses of gout. The Hmong group was younger (58.3 vs. 66.3 years, P = 0.04), had an earlier onset of symptoms (37.4 vs. 55.0 years, P < 0.001) and higher mean serum uric acid levels during follow-up (9.1 vs. 7.6 mg/dL, P < or = 0.001). Hmong had higher rates of tophaceous gout (31.5% vs. 10.7%, P = 0.001), including hand tophi (21.3% vs. 3.6%, P < 0.001). In multivariable analyses that adjusted for age, sex, hypertension, diuretic, use, and kidney function, Hmong ethnicity was significantly associated with risk of tophaceous gout, with odds ratio 4.3 (95% confidence interval: 1.5, 12.2).. Hmong patients have an earlier onset of gout symptoms. Hmong race is an independent risk factor for tophaceous gout. Future studies need to examine whether genetic or other comorbid factors predict this higher risk of more severe gout in Hmong.

Topics: Aged; Allopurinol; Asian; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; United States; White People

Topics: Adult; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Drug Therapy, Combination; Foot; Gout; Hand; Humans; Male; Steroids; Tomography, X-Ray Computed

To enable clinicians to initiate appropriate steps for long-term management of gout, including controlling acute exacerbations and pain and sustaining target serum uric acid (SUA) levels to control hyperuricemia as the underlying metabolic disorder.. Incorporation of pertinent rheumatology and primary care literature seeking a comprehensive overview about the disease state of gout and its symptoms, comorbidities, and impact on quality of life, with a key focus on the role of serum uric acid, evidence-based approaches to long-term management of gout, and the importance of a functioning clinician-patient relationship.. Gout is increasingly recognized as a prevalent chronic disease state requiring appropriate long-term management while controlling for risk factors and comorbid conditions. Effective treatment options can help gout patients achieve therapeutic SUA targets to control gout flares and prevent potentially destructive disease manifestations. Patient education is an important element in achieving treatment goals and ensuring adherence.. Effective treatment plans for any gout patient must be guided by a long-term approach that focuses on sustained control of hyperuricemia, while providing continuous control of chronic disease. Patient education can be a key element in this process.

Topics: Acute Disease; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Arthritis, Rheumatoid; Chronic Disease; Colchicine; Comorbidity; Disease Progression; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Patient Education as Topic; Quality of Life; Risk Factors; Thiazoles; Uric Acid; Uricosuric Agents; Xanthine Oxidase

To study patterns and predictors of medication use and laboratory monitoring in gout.. In a cohort of veterans with a diagnosis of gout prescribed allopurinol, colchicine or probenecid, quality of care was assessed by examining adherence to the following evidence-based recommendations: (1) whether patients starting a new allopurinol prescription (a) received continuous allopurinol, (b) received colchicine prophylaxis, (c) achieved the target uric acid level of

Topics: Aged; Allopurinol; Biomarkers; Colchicine; Drug Administration Schedule; Drug Monitoring; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Male; Middle Aged; Practice Guidelines as Topic; Probenecid; Quality of Health Care; Renal Insufficiency; Treatment Outcome; Uric Acid

Gout and pain are synonymous, and a study in this issue of the BJP reports a novel anti-nociceptive effect of allopurinol, the drug most commonly used to treat gout. Allopurinol works by inhibiting xanthine oxidase (XO), the enzyme responsible for converting hypoxanthine to uric acid which is deposited as crystals in the joints of gout sufferers. Hypoxanthine is a metabolite of, and a possible precursor to, adenosine. Schmidt et al., find that acute inhibition of XO with allopurinol produces a modest adenosine A(1) receptor-mediated anti-nociceptive effect in common tests of chemical and thermal nociception in mice. A concomitant increase in cerebrospinal fluid levels of adenosine supports their hypothesis that inhibiting XO increases adenosine levels via salvage from hypoxanthine. Elevating endogenous adenosine levels by inhibiting metabolism is a well-established strategy for producing anti-nociception in many preclinical models, but inhibiting XO is likely to be particularly beneficial in some chronic pain states because of the pro-nociceptive reactive oxygen species that are produced by XO activity. Thus, allopurinol may have unexpected benefits in pain associated with chronic inflammation, diabetes and vascular dysfunction.

Topics: Adenosine; Adenosine A1 Receptor Agonists; Allopurinol; Analgesics; Animals; Gout; Mice; Pain; Reactive Oxygen Species; Xanthine Oxidase

Alkaptonuria is an inborn error of amino acid metabolism. A defect in tyrosine metabolism that results in accumulation of homogentisic acid in connective tissue, especially cartilage, has long been known. Degenerative arthropathy, especially of the knee and spine, develops at a relatively early age in adults. Accumulation also occurs in heart valves, and there may be a predisposition to atherosclerosis. We describe a 72-year-old man with ochronosis, gouty arthritis of both hands, and monckeberg arteries.

Topics: Aged; Allopurinol; Anti-Inflammatory Agents; Gout; Gout Suppressants; Hand; Humans; Male; Monckeberg Medial Calcific Sclerosis; Ochronosis; Prednisolone; Radiography

To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout.. Subjects (n=1086) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment (ULT) with febuxostat (80 mg or 120 mg) or allopurinol (300 mg). ULT reassignment was permitted during months 1 to 6 to achieve serum urate (SUA) concentrations between 3.0 and <6.0 mg/dl. Flares requiring treatment, tophus size, safety, and SUA levels were monitored during up to 40 months of ULT maintenance.. After 1 month initial treatment, >80% of subjects receiving either febuxostat dose, but only 46% of subjects receiving allopurinol, achieved SUA<6.0 mg/dl. After ULT reassignment, >80% of all remaining subjects maintained the primary efficacy endpoint of SUA<6.0 mg/dl at each visit. More subjects initially randomized to allopurinol required ULT reassignment to achieve SUA<6.0 mg/dl compared with subjects receiving febuxostat. Maintenance of SUA<6.0 mg/dl resulted in progressive reduction to nearly 0 in proportion of subjects requiring gout flare treatment. Baseline tophus resolution was achieved by 46%, 36%, and 29% of subjects maintained on febuxostat 80 mg, febuxostat 120 mg, and allopurinol, respectively. Overall adverse event rates (including cardiovascular adverse event rates), adjusted for 10-fold greater febuxostat than allopurinol exposure, did not differ significantly among treatment groups.. Durable maintenance of goal range SUA level with either dose of febuxostat or in smaller numbers of subjects with allopurinol resulted in near elimination of gout flares and improved tophus status over time. Registered as NCT00175019.

Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Hyperuricemia; Thiazoles; Treatment Outcome; Uric Acid

Topics: Administration, Oral; Drug Approval; Drug Interactions; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles; United States; United States Food and Drug Administration; Uric Acid; Xanthine Oxidase

Adherence to urate-lowering drugs (ULDs) has not been well evaluated among those with gout. Our aim was to assess the level and determinants of non-adherence with ULDs prescribed for gout.. We identified persons using two integrated delivery systems aged 18 years or older with a diagnosis of gout who initiated use of allopurinol, probenecid or sulfinpyrazone from 1 January 2000 to 30 June 2006. Non-adherence was measured using the medication possession ratio (MPR) over the first year of therapy and defined as an MPR < 0.8. Descriptive statistics were calculated and logistic regression was used to estimate the strength of the association between patient characteristics and non-adherence.. A total of 4,166 gout patients initiated ULDs; 97% received allopurinol. Median MPR for any ULD use was 0.68 (interquartile range (IQR) 0.64). Over half of the patients (56%) were non-adherent (MPR < 0.8). In adjusted analyses, predictors of poor adherence included younger age (odds ratio (OR) 2.43, 95% confidence interval (CI) 1.86 to 3.18 for ages <45 and OR 1.44, 95% CI 1.08 to 1.93 for ages 45 to 49), fewer comorbid conditions (OR 1.46, 95% CI 1.20 to 1.77), no provider visits for gout prior to urate-lowering drug initiation (OR 1.28, 95% CI 1.05 to 1.55), and use of non-steroidal anti-inflammatory drugs in the year prior to urate-lowering drug initiation (OR 1.15, 95% CI 1.00 to 1.31).. Non-adherence amongst gout patients initiating ULDs is exceedingly common, particularly in younger patients with less comorbidity and no provider visits for gout prior to ULD initiation. Providers should be aware of the magnitude of non-adherence with ULDs.

Topics: Age Factors; Allopurinol; Female; Gout; Gout Suppressants; Humans; Male; Medication Adherence; Middle Aged; Probenecid; Sulfinpyrazone; Uric Acid

The purine contents of alcoholic beverages were determined in order to utilize them in the dietary care of gout and hyperuricemia. In the management of these diseases, restriction of both alcohol and purine intake are important. The method employed in this study is a quantitative determination of purine contents by HPLC. Alcoholic beverages were hydrolyzed to corresponding purine bases, which were then separated by HPLC, and base peaks were identified using an enzymatic peak-shift technique. This method is sufficiently accurate and reproducible to examine the purine contents of various alcoholic beverages that patients consume. Purine contents were as follows: spirits, 0.7-26.4 micromol/L; regular beer, 225.0-580.2 micromol/L; low-malt beer, 193.4-267.9 micromol/L; low-malt and low-purine beer, 13.3 micromol/L; other liquors, 13.1-818.3 micromol/L. Some local and low-alcohol beers were found to contain about 2.5 times more purines than regular beer. As some alcoholic beverages contain considerable amounts of purines, we recommend that excess consumption of these beverages be avoided. These data should be useful in the management of hyperuricemia and gout, not only for patients but also for physicians.

Topics: Alcoholic Beverages; Chromatography, High Pressure Liquid; Gout; Guanine Deaminase; Humans; Hyperuricemia; Purines; Reproducibility of Results; Sensitivity and Specificity; Xanthine Oxidase

Topics: Adenine Phosphoribosyltransferase; Adult; Allopurinol; DNA Mutational Analysis; Genotype; Gout; Gout Suppressants; HLA-B Antigens; Humans; Male; Mutation; Treatment Outcome

While studies have suggested that gout and hyperuricaemia are associated with the risk of premature death, none has investigated the role of urate-lowering therapy on this critical outcome. We examined the impact of allopurinol, the most commonly used urate-lowering drug, on the risk of mortality in hyperuricaemic patients.. From a population of hyperuricaemic veterans of [serum urate level >416 micromol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n = 2483) and non-users (n = 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models.. Of the 9924 veterans (males, 98% and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95% CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95% CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was -111 micromol/l (-1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 micromol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95% CI -0.55, -0.81).. Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Time Factors; Treatment Outcome; Veterans

Topics: Adult; Allopurinol; Azathioprine; Clostridioides difficile; Colitis, Ulcerative; Crohn Disease; Drug Interactions; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Gout; Gout Suppressants; Histoplasmosis; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Psoas Abscess; Tumor Necrosis Factor-alpha

To assay the in vitro xanthine oxidase inhibitory activity of the various fractions of the hydromethanolic extract of the leaves of Erythrina stricta and to determine its enzyme inhibition mechanism.. Xanthine oxidase inhibitory activity was assayed spectrophotometrically under aerobic conditions and the degree of enzyme inhibition was determined by measuring the increase in absorbance at 295 nm associated with uric acid formation. Enzyme kinetics was carried out using Lineweaver-Burk plots using xanthine as the substrate.. Among the fractions tested, the chloroform fraction exhibited highest potency (IC(50) 21.2+/-1.6 microg/ml) followed by the pet-ether (IC(50) 30.2+/-2.2 microg/ml), ethyl acetate (IC(50) 44.9+/-1.4 microg/ml) and residual (IC(50) 100+/-3.3 microg/ml) fractions. The IC(50) value of allopurinol used, as the standard was 6.1+/-0.3 microg/ml. Enzyme inhibition mechanism indicated that the mode of inhibition was of a mixed type.. These results suggest that the use of Erythrina stricta for the treatment of gout could be attributed to its xanthine oxidase inhibitory activity.

Topics: Acetates; Allopurinol; Chloroform; Enzyme Inhibitors; Erythrina; Ethers; Gout; Kinetics; Plant Extracts; Plant Leaves; Solvents; Xanthine Oxidase

To determine the association between allopurinol compliance and serum urate (sUA) level; and examine the association between sUA and gout-related healthcare costs in a large managed care population.. This retrospective administrative claims analysis examined subjects with gout (> or = 2 medical claims with ICD-9-CM diagnosis code 274.xx or > or = 1 claim with a gout diagnosis and > or = 1 pharmacy claim for allopurinol, probenecid, colchicine, or sulfinpyrazone) between January 1, 2002 and March 31, 2004. Each subject was observed during 1-year pre-index and 1-year post-index periods.. Outcomes were allopurinol medication possession ratio (MPR) and compliance (MPR > or = 0.80), sUA (mg/dL), and gout-related healthcare costs. 'Post-allopurinol' sUA was measured during three periods after the first observed allopurinol fill: 30-89 days; 90-149 days; > or = 150 days. A baseline sUA on or before the start of the post-index period was also identified. Outcomes were stratified by post-allopurinol or baseline sUA and compliance. Generalized linear modeling (GLM) regression measured the impact of baseline sUA on gout-related healthcare costs, controlling for demographic and health status variables.. The study sample comprised 18,243 subjects with mean age of 53.9 years. In all, 55% (n = 10,073) of subjects used allopurinol. There were 1473 (8.1%) subjects with a post-allopurinol sUA and 2438 (13.4%) subjects with a baseline sUA result. Among all subjects with a post-allopurinol sUA, 45.6% were compliant; between 49.3% and 56.8% of compliant subjects had an sUA < 6.0 mg/dL compared with 22.5-27.8% of non-compliant subjects, depending on the post-allopurinol time period (all p < 0.001). GLM results showed gout-related costs associated with baseline sUA > or = 6.0 and < 9.0 mg/dL were 58% higher (95% confidence interval (CI): 1.012 -2.456; p = 0.044) than were costs for sUA < 6.0 mg/dL. There was no significant difference in gout-related costs between baseline sUA < 6.0 mg/dL and > or = 9.0 mg/dL.. Analysis revealed an important associations between allopurinol compliance, sUA, and gout-related costs: compliance was positively associated with favorable sUA (<6.0 mg/dL) in unadjusted comparisons. GLM showed that baseline sUA < 6.0 was inversely associated with gout-related costs relative to baseline sUA > or = 6.0 and <9.0 mg/dL. Nevertheless, a substantial portion of subjects, even compliant ones, did not achieve sUA < 6.0 mg/dL. These results should be interpreted carefully in light of study limitations, including incomplete laboratory data, the potentially incorrect inference that medications were taken as prescribed, and lack of generalizability from Medicare managed care enrollees to the broader Medicare population.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Drug Therapy, Combination; Female; Gout; Health Care Costs; Humans; Insurance Claim Review; Male; Middle Aged; Patient Compliance; Uric Acid; Uricosuric Agents; Young Adult

(1) For patients with chronic symptomatic hyperuricaemia who fail to respond to a low purine diet, allopurinol is the standard drug used to prevent complications. This xanthine oxidase inhibitor can, in rare instances, cause severe skin reactions. Probenecid, a uricosuric agent, with which there is also long experience, is a second-line option; (2) Febuxostat, another xanthine oxidase inhibitor, is now authorized for the treatment of hyperuricaemia; (3) Two randomised double-blind trials in 762 and 1072 patients tested various doses of febuxostat compared with a standard dose of allopurinol (33 mg/day). Febuxostat normalised uric acid levels more frequently than allopurinol. However, overall, more patients suffered gout attacks with febuxostat than with allopurinol during the first two months of treatment, despite preventive measures (30-35% versus 22%). Between 3 and 6 months of treatment neither drug reduced the incidence of gout attacks more effectively than placebo. After one year of treatment about two-thirds of patients suffered gout attacks, with no difference between the febuxostat and allopurinol groups; (4) In these trials there were more premature treatment withdrawals with febuxostat than with allopurinol; (5) The adverse effects of febuxostat are poorly documented, especially cardiac, hepatic, haematological and thyroid disorders. In the short term, severe cardiac disorders, based on a composite endpoint, were 4 to 5 times more frequent with febuxostat than with allopurinol. Treatment withdrawals due to hepatic disorders were more frequent with febuxostat than with allopurinol (2.8% versus 0.4%). The relative frequency of severe cutaneous disorders with febuxostat and allopurinol is not known; (6) Clinical evaluation does not include any head-to-head trials of febuxostat versus probenecid; (7) In practice, patients with hyperuricaemia should continue to receive allopurinol as first-line treatment, and probenecid as second-line treatment if allopurinol is ineffective.

Topics: Allopurinol; Drug Approval; Europe; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Randomized Controlled Trials as Topic; Thiazoles

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Allopurinol; Angioedema; Diuretics; Drug Hypersensitivity; Exanthema; Gout; Histamine Antagonists; Humans; Hypertension; Hyperuricemia; Liver Failure, Acute; Male; Oxygen Inhalation Therapy; Renal Insufficiency

Although gout has recognized prevention and treatment options, some patients have recurrent unplanned hospital admissions with gout flares. The aim of this study was to identify factors associated with recurrent hospital admissions with gout.. A 1:1 case-control study was designed; cases were patients with 2 or more gout-related hospital admissions during any 12-month period between 2002 and 2007 (n = 48). Each case was matched with an age, sex and ethnicity-matched control patient with gout but without hospital admission, identified from the rheumatology clinic (n = 48).. Patients with recurrent hospital admissions had a higher number of comorbid medical conditions, particularly higher rates of heart disease (odds ratio 2.9, P = 0.013). Cases also had more hospital admissions for other medical problems (mean number of admissions in the preceding year 5.8 vs. 0.6, P < 0.0001). Although cases had higher rates of tophaceous disease and higher serum urate concentrations, there was no difference in gout disease duration. Cases were less likely to be on allopurinol (odds ratio 0.06, P < 0.0001), and those on allopurinol were on lower doses (median dose 200 mg/d vs. 300 mg/d, P = 0.0019).. Medical comorbidity, hyperuricemia, and inadequate allopurinol use are associated with repeated unplanned hospitalization for gout. These data suggest that the use of intensive urate-lowering therapy may prevent such admissions.

Topics: Adult; Aged; Allopurinol; Case-Control Studies; Comorbidity; Dose-Response Relationship, Drug; Female; Gout; Gout Suppressants; Heart Diseases; Hospitalization; Humans; Hyperuricemia; Male; Middle Aged; New Zealand; Prevalence; Quality of Health Care; Recurrence; Retrospective Studies; Risk Factors

Topics: Allopurinol; Drug Hypersensitivity; Gout; Gout Suppressants; Humans; Monitoring, Physiologic; Nephrology; Risk; Treatment Outcome

The aim of this study was to ascertain the management of gout by doctors in Malaysia.. A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.. A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.. In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines.

Topics: Acute Disease; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Colchicine; Cross-Sectional Studies; Cyclooxygenase 2 Inhibitors; Glucocorticoids; Gout; Gout Suppressants; Humans; Malaysia; Primary Health Care; Professional Practice; Reference Values; Surveys and Questionnaires; Uric Acid

Topics: Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents; Diffusion Magnetic Resonance Imaging; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Low Back Pain; Lumbar Vertebrae; Prednisone; Uric Acid

Epidemiologic and recent qualitative research suggests that the impact of under-treated gout is far more significant than many health professionals realise. The magnitude of this impact for Maaori and Pacific men of working age has been identified as a particular concern by the recently formed Maaori Gout Action Group in Counties Manukau District Health Board (South Auckland, New Zealand). The Group has identified that to achieve modern management of gout, those with gout need to be supported by primary care practitioners who are aware of the need for early intervention with allopurinol, as well as whaanau/families and communities who understand the impact and causes of gout and the lifestyle changes that are needed alongside long-term allopurinol. The Group wishes to support further research into the impact and causes of gout, particularly for Maaori, and to develop strategic alliances to ensure that the treatment and prevention of gout is advocated by those working with conditions such as diabetes and cardiovascular disease where gout is a frequent comorbidity.

Topics: Adolescent; Adult; Allopurinol; Cross-Sectional Studies; Culture; Early Diagnosis; Forecasting; Gout; Gout Suppressants; Health Education; Health Knowledge, Attitudes, Practice; Health Promotion; Humans; Life Style; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Primary Health Care; Risk Factors

A study was conducted to determine whether combination treatment using allopurinol and benzbromarone was more useful than single allopurinol treatment for the gout and hyperuricemia accompanying renal dysfunction. The subjects were 45 male patients who received urate-lowering treatment and showed a stable serum urate level. The patients were divided into four groups according to the urate-lowering treatment and creatinine clearance (Ccr) (A group: single treatment, normofunction, B group: single treatment, hypofunction, C group: combined treatment, normofunction, D group: combined treatment, hypofunction). There were no differences in serum urate levels among the four groups. Urate clearance (CUA)and daily urinary urate excretion (UUAV) showed significantly high values in the C group, but no difference was seen in the fractional excretion of urate (FEUA) among the four groups. The dosage of allopurinol in the D group was significantly lower than in the A and B groups. Serum oxypurinol concentration in the C group was lower than that in the B group. Oxypurinol clearance (C oxypurinol) in the C group was significantly high compared with the B and D groups. There was a close correlation between C oxypurinol, Ccr, and CUA, with an especially strong correlation between C oxypurinol and CUA. There were no differences in the serum concentration and clearance of xanthine and hypoxanthine among the four groups. Results of the study suggested that combination treatment using allopurinol and benzbromarone for the gout and hyperuricemia accompanying renal dysfunction is more useful, because a lower dose of allopurinol can be used and the serum oxypurinol concentration is reduced compared with single allopurinol treatment.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Oxypurinol; Retrospective Studies

Topics: Allopurinol; Body Mass Index; Combined Modality Therapy; Gout; Humans; Life Style; Male; Middle Aged; Risk Factors; Secondary Prevention; Uricosuric Agents; Weight Loss

Topics: Allopurinol; Clinical Trials as Topic; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Treatment Failure; Urate Oxidase

Topics: Administration, Oral; Allopurinol; Dose-Response Relationship, Drug; Drug Evaluation; Europe; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles; Uric Acid; Xanthine Oxidase

A 67-year-old man presented to a rheumatology clinic with a 1-week history of severe pain and swelling of his right knee. He had been receiving allopurinol for about 5 months for the treatment of chronic gouty arthropathy of more than 30 years' duration. On examination, his right knee was warm and swollen. The aspirated fluid contained intracellular and extracellular monosodium urate crystals, but Gram staining and culture were negative. The affected knee was injected with triamcinolone, but the patient continued to experience severe pain and complained of locking of the knee 3 weeks after the onset of his initial symptoms. Physical examination at this time showed no sign of inflammation, but the knee had a very limited range of motion.. Physical examination; routine laboratory investigations, including CBC, complete metabolic panel, measurement of serum uric acid levels, and synovial fluid analysis; radiological investigations, including radiography of the right knee and CT of the right knee with intra-articular contrast.. CT showed no internal derangement, but revealed extensive intra-articular and extra-articular amorphous soft tissue calcifications, compatible with gouty tophi.. The patient declined an arthroscopic procedure to remove the gouty tophi. Treatment consisted of continuous allopurinol therapy and narcotics for symptomatic pain relief. Over the next 12 months, the patient's serum uric acid levels, and presumably his total-body urate pool, were substantially reduced. The knee unlocked and the pain subsided. Follow-up CT about 3 years after the initial examination showed complete resolution of the calcified intra-articular and extra-articular tophi.

Topics: Aged; Allopurinol; Arthralgia; Gout; Gout Suppressants; Humans; Knee Joint; Male; Radiography

Uric acid lowering therapy (UALT) is considered a chronic treatment for gout. Relatively little is known about adherence to UALT.. We assessed adherence with UALT over a 1-year study period among 9823 older adults enrolled in a pharmacy benefit program. Two adherence measures were calculated, the percentage of days covered (PDC) and the time until an extended break (at least 60 days) in treatment. A PDC <80% was considered poor adherence and its predictors were examined in multivariable logistic models.. The mean (SD) PDC was 54% (36%) with 64% of patients considered poorly compliant over the study period. A total of 56% had experienced an extended break in UALT. Predictors of poor adherence included younger age (odds ratio (OR) 1.50, 95% CI 1.33-1.69 for ages 65-74 compared with 85 and above) and African-American race (OR 1.86, 95% CI 1.52-2.27 compared with Caucasian race). Most patients (93%) received their initial UALT prescription from a non-specialist and this also predicted poor adherence (OR 1.15, 95% CI 0.96-1.38 compared with rheumatologists or nephrologists).. Adherence with UALT is poor. While uric acid levels were not measured in this study, poor adherence with UALT is likely to reduce attainment of goal uric acid levels.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Black or African American; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Humans; Logistic Models; Male; Massachusetts; Patient Compliance; Probenecid; Sulfinpyrazone; White People

To investigate and compare the prevalence, comorbidities and management of gout in practice in the UK and Germany.. A retrospective analysis of patients with gout, identified through the records of 2.5 million patients in UK general practices and 2.4 million patients attending GPs or internists in Germany, using the IMS Disease Analyzer.. The prevalence of gout was 1.4% in the UK and Germany. Obesity was the most common comorbidity in the UK (27.7%), but in Germany the most common comorbidity was diabetes (25.9%). The prevalence of comorbidities tended to increase with serum uric acid (sUA) levels. There was a positive correlation between sUA level and the frequency of gout flares. Compared with those in whom sUA was <360 micromol/l (<6 mg/dl), odds ratios for a gout flare were 1.33 and 1.37 at sUA 360-420 micromol/l (6-7 mg/dl), and 2.15 and 2.48 at sUA >530 micromol/l ( >9 mg/dl) in the UK and Germany, respectively (p<0.01).. The prevalence of gout in practice in the UK and Germany in the years 2000-5 was 1.4%, consistent with previous UK data for 1990-9. Chronic comorbidities were common among patients with gout and included conditions associated with an increased risk for cardiovascular disease, such as obesity, diabetes and hypertension. The importance of regular monitoring of sUA in order to tailor gout treatment was highlighted by data from this study showing that patients with sUA levels >or=360 micromol/l (>or=6 mg/dl) had an increased risk of gout flares.

Topics: Aged; Allopurinol; Drug Administration Schedule; Drug Monitoring; Epidemiologic Methods; Family Practice; Female; Germany; Gout; Gout Suppressants; Humans; Male; Middle Aged; Recurrence; United Kingdom; Uric Acid

Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 microg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC (50) > 100 microM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC (50) value of 1.49 microM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC (50) values of 19.90 microM and 20.24 microM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.

Topics: Administration, Oral; Animals; Cynara scolymus; Flavonoids; Gout; Hyperuricemia; Male; Oxonic Acid; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

Topics: Aged; Allopurinol; Constriction, Pathologic; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Male; Spinal Cord Diseases; Thoracic Vertebrae

Pistacia integerrima Stew ex. Brandis is an important component of commonly dispensed traditional dosage forms. We wished to determine whether polyphenolic constituents of this plant could be useful in oxidative stress and have potential to counter hyperuricemia.. Radical scavenging activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and xanthine oxidase (XO) inhibitory activity assay in vitro. Fructose (FRS) induced hyperuricemic animal model was used to asses the serum uric acid (UA) lowering effect by plant products.. Ethyl acetate and n-BuOH fractions had the highest DPPH radical scavenging activity. Fifty percent inhibitory concentration (IC(50)) was 6 and 7.6 microg/ml respectively. It was less than quercetin (IC(50) 0.95 microg/ml) and ascorbic acid (IC(50) 1.76 microg/ml). Xanthine oxidase inhibitory activity was comparable between n-BuOH and EtOAc (IC(50) 19 and 20 microg/ml) extracts but less than quercetin (IC(50) 0.65 microg/ml) and allopurinol (IC(50) 0.10 microg/ml). The antioxidant activity as well as the inhibitory activity towards the enzyme XO by quercetin-3-O-beta-d-glucopyranoside (5), kaempferol-3-O-beta-d-glucopyranoside (6), quercetin-3-O-(6''-O-syringyl)-beta-d-glucopyranoside (7), kaempferol-3-O-(4''-O-galloyl)-alpha-l-arabinopyranoside (8), rutin (4) together with aglycons, quercetin (1), kaempferol (2) and apigenin (3) was promising to continue in vivo hypouricemic studies. Ethyl acetate extract had dose dependent UA lowering effect in hyperuricemic mice. This effect was comparable with quercetin but less than allopurinol.. These findings are encouraging to plan clinical studies in hyperuricemic patients.

Topics: 1-Butanol; Animals; Area Under Curve; Biphenyl Compounds; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ethanol; Free Radical Scavengers; Gout; Gout Suppressants; Hyperuricemia; Male; Mice; Mice, Inbred BALB C; Picrates; Pistacia; Plant Extracts; Plant Leaves; Solvents; Xanthine Oxidase

International data suggest that suboptimal use of allopurinol is common. Allopurinol dose should be lower in renal impairment, but higher when gout is not controlled. The aim of the study was to examine trends in the usage of allopurinol in the Australian community.. Community dispensing data on the urate-lowering drugs allopurinol and probenecid were obtained from databases kept by Medicare Australia and the Drug Utilization Sub-Committee, for January 1992 to December 2005.. Allopurinol comprised 98.4% of all prescriptions for urate-lowering drugs dispensed during 2005. Most prescriptions were for allopurinol 300 mg, but there was a steady shift towards use of allopurinol 100 mg in all states and territories over the period of the study. There were marked variations in prescribing rates across the country. New South Wales had the highest rate of subsidized prescribing for allopurinol 300 mg (39.3 per 1000 population). Tasmania had the highest rate for allopurinol 100 mg (14.3 per 1000 population), which coincided with an educational programme to decrease allopurinol dose in patients with renal impairment. Prescribing rates in the Northern Territory were substantially lower than all other regions, at 10.8 and 3.3 prescriptions per 1000 population for allopurinol 300 and 100 mg, respectively.. The increased uptake of allopurinol 100 mg suggests greater adherence to dosing guidelines and that there is value in educational programmes to optimize drug usage. Variability in utilization rates across regions indicates the need for research on factors responsible. Precise understanding of dosing trends requires access to deidentified, individual dosing data.

Topics: Allopurinol; Australia; Community Health Services; Drug Prescriptions; Drug Utilization; Gout; Gout Suppressants; Guideline Adherence; Humans; Retrospective Studies