mobic and Arthritis--Rheumatoid

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries.. Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator.. Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables.. We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/15. We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Arthritis, Rheumatoid; Aspirin; Celecoxib; Child; Child, Preschool; Chronic Disease; Chronic Pain; Fenoprofen; Humans; Ibuprofen; Lactones; Meloxicam; Methoxsalen; Naproxen; Randomized Controlled Trials as Topic; Sulfones; Thiazines; Thiazoles

The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of approximately 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug-drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase 2 Inhibitors; Drug Interactions; Gastrointestinal Diseases; Humans; Meloxicam; Thiazines; Thiazoles

Rheumatoid arthritis (RA), a chronic inflammatory multisystem disorder marked by joint pain, stiffness, swelling and multiple systemic involvements, requires a multifaceted approach for its management. It includes symptomatic treatment with analgesics as well as disease-modifying medications to alter the course of RA over time. NSAIDS have been widely used for their symptomatic effects, but their use is not free from adverse effects, which may include life-threatening adverse events such as gastrointestinal (GI) bleeding and perforation. Meloxicam, an oxicam derivative that is a member of the enolic acid group of NSAIDs, has recently been approved by the US FDA for use in RA and osteoarthritis. At the FDA-recommended doses meloxicam is COX-2 preferential. By virtue of this COX-2 preferential activity it is expected to have lower GI toxicity as compared with COX-2 nonselective NSAIDs. Clinical trials have shown that meloxicam at 7.5 - 15 mg/day is as effective as diclofenac, piroxicam and naproxen as an anti-inflammatory and analgesic, and was associated with fewer GI adverse effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cardiovascular System; Cyclooxygenase Inhibitors; Gastrointestinal Tract; Humans; Kidney; Meloxicam; Thiazines; Thiazoles

To observe the rate of efficacy and adverse drug reaction of non-steroidal anti-inflammatory drugs (NSAIDs) in the population with osteoarthritis and rheumatoid arthritis, based on available clinical data.. Using Meta analysis to evaluate the data of effect and safety profile of NSAIDs from 19 articles on randomized clinical trials published from 1990 to 2001 in Chinese journals. The total number of patients enrolled for evaluation on rates of effectiveness and adverse drug reaction were 1 732 and 2 925, respectively.. Data on the effect and safety were comparatively heterogeneous among different kinds of NSAIDs. The effective rates (95% CI) were as follows: nabunetone, 66.7% (61.9% - 71.4%); meloxicam, 68.4% (59.2% - 77.6%); naproxen, 64.5% (59.8% - 69.1%); nimesulide, 79.8% (75.7% - 84.0%); ibuprofen, 77.2% (70.7% - 83.8%); diclofenac, 77.1% (69.2% - 85.0%); oxaprozin, 65.8% (59.5% - 72.0%). Rates of adverse drug reaction (95% CI) were as follows: nabunetone, 16.3% (12.5% - 20.0%); meloxicam, 10.2% (4.2% - 16.2%); naproxen, 29.2% (24.8% - 33.6%); nimesulide, 20.2% (16.0% - 24.3%); ibuprofen, 16.7% (14.7% - 18.8%); diclofenac, 19.3% (11.9% - 26.7%); oxaprozin, 12.7% (8.9% - 16.7%) respectively.. The rates of effect and adverse reaction on patients having osteoarthritis and rheumatoid arthritis with NSAIDs treatment would largely depend on the drugs being used. Within 2 - 8 weeks of treatment, the effective rate and rate of adverse drug reaction with commonly used NSAIDs as nabumeton, meloxicam, etc., were 59.2% - 85.0% and 4.2% - 33.6%, respectively.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; China; Diclofenac; Humans; Ibuprofen; Meloxicam; Nabumetone; Naproxen; Osteoarthritis; Oxaprozin; Propionates; Randomized Controlled Trials as Topic; Sulfonamides; Thiazines; Thiazoles

Meloxicam (Mobic trade mark, Boehringer Ingelheim) is a relatively new oral non-steroidal anti-inflammatory drug (NSAID) approved for the treatment of osteoarthritis in the US. It has also been evaluated for the treatment of rheumatoid arthritis, ankylosing spondylitis and acute 'rheumatic' pain. Meloxicam has been shown to be COX-2 preferential, particularly at its lowest therapeutic dose, and is anti-inflammatory by inhibiting prostanoid synthesis in inflammatory cells. Since it is COX-2 preferential, it would be expected to have less gastrointestinal toxicity than non-selective NSAIDs. In clinical trials of meloxicam in osteoarthritis, it was found to be as effective as piroxicam, diclofenac and naproxen with less clinical gastrointestinal symptoms and less perforations, obstructions and bleeds by meta-analysis. Adverse events, including peripheral oedema and hypertension, occurred at a similar rate as with traditional NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Interactions; Humans; Meloxicam; Osteoarthritis; Pain; Product Surveillance, Postmarketing; Spondylitis, Ankylosing; Thiazines; Thiazoles

Meloxicam (Mobic) is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid, exhibiting selectivity for cyclooxygenase (COX)-2 over COX-1. Meloxicam has shown potent anti-inflammatory and analgesic activity together with low gastrointestinal toxicity in animal models. It is a potent inhibitor not only of acute exudation in adjuvant arthritis in the rat, but also of bone and cartilage destruction. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of other NSAIDs. Meloxicam in therapeutic doses was found to have no effect on bleeding time or platelet aggregation in healthy volunteers. In clinical studies, meloxicam has shown reliable efficacy against rheumatoid arthritis, osteoarthritis, lumbago (low back pain), scapulohumeral periarthritis, and neck-shoulder-arm syndrome with low gastrointestinal toxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 2; Enzyme Inhibitors; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Inflammation; Isoenzymes; Meloxicam; Membrane Proteins; Pain; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Rats; Thiazines; Thiazoles

NSAID's are currently medications widely prescribed. Meloxicam is a new oxicam which has a low COX-2/COX-1 ratio, i.e. it has an inhibitory effect focused on the inflammatory proteins (COX-2) with relative saving of the homeostatic proteins (COX-1). This molecule has been studied in three rheumatic diseases, the acute flare-up of osteoarthritis, rheumatoïd arthritis, and ankylosing spondylitis. The results show that meloxicam is as effective as comparative NSAID's. A global analysis of the data from more than 5000 patients included in clinical trials showed that gastro-intestinal tolerance of meloxicam was better than that of comparative NSAID'S. Nevertheless, the clinical translation of the anti-COX-2 selectivity concept is currently debated.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Rheumatoid; Biological Availability; Cyclooxygenase Inhibitors; Drug Interactions; Humans; Meloxicam; Spondylitis, Ankylosing; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Humans; Meloxicam; Osteoarthritis; Spondylitis, Ankylosing; Thiazines; Thiazoles

Nonsteroid antiinflammatory drugs (NSAIDs) or aspirin-like drugs act by inhibiting the activity of the cyclooxygenase (COX) enzyme. Two isoforms of COX exist, COX-1, which is constitutively expressed, and COX-2, which is an inducible isoform. Prostaglandins synthesized by the constitutively expressed COX-1 are implicated in the maintenance of normal physiological function and have a 'cytoprotective' action in the stomach. COX-2 expression is normally low but is induced by inflammatory stimuli and cytokines. It is thought that the antiinflammatory actions of NSAIDs are caused by the inhibition of COX-2, whereas the unwanted side effects, such as gastrointestinal and renal toxicity, are caused by the inhibition of the constitutively expressed COX-1. Individual NSAIDs show different selectivities against the COX-1 and COX-2 isoforms. NSAIDs that are selective towards COX-2, such as meloxicam, may have an improved side-effect profile over current NSAIDs. In addition to their use as antiinflammatory agents in the treatment of rheumatoid arthritis and osteoarthritis, selective COX-2 inhibitors may also be beneficial in inhibiting colorectal tumor cell growth and in delaying premature labor.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Isoenzymes; Meloxicam; Membrane Proteins; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thiazines; Thiazoles

Rheumatological conditions often give rise to gastrointestinal (GI) symptoms and vice versa, but the greatest point of contact between rheumatologists and gastroenterologists arises through gastrointestinal toxicity resulting from the use of nonsteroidal antiinflammatory drugs (NSAIDs). Standard NSAIDs are toxic to the entire GI tract. The point prevalence of ulcers in patients on long-term NSAID treatment is about 20% and the annual incidence of complications in these patients is 1% to 4%; 1,200 patients in the United Kingdom die each year as a result. Withdrawing NSAID treatment, or reducing the dose, is not always possible, and approximately 25% of patients require continued long-term antiinflammatory treatment. Misoprostol and acid-suppressing drugs such as ranitidine and omeprazole are helpful as prophylactic treatment in high risk patients, and in healing established ulcers, especially in patients carrying Helicobacter pylori, but there is a pressing need for new, safer antiinflammatory drugs toease the burden of NSAID gastropathy. Selective inhibition of the COX-2 isoform of cyclooxygenase has been proposed as a new and safer therapeutic option. Clinical studies with meloxican, a selective COX-2 inhibitor, support this view. Meloxicam has been extensively studied in arthritis patients and combines antiinflammatory efficacy with a lower incidence of GI toxicity than currently available NSAIDs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Digestive System; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Meloxicam; Rats; Stomach Ulcer; Thiazines; Thiazoles

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibiting cyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with improved tolerability. In volunteers, indomethacin 75 mg, but not meloxicam 7.5 mg, inhibited renal prostaglandin E2 excretion and platelet aggregation (COX-1 mediated effects). Double-blind, randomized trials in osteoarthritis and rheumatoid arthritis patients have shown equivalent antiinflammatory efficacy among meloxicam 7.5 mg or 15 mg and diclofenac 100 mg, naproxen 750 mg, and piroxicam 20 mg. In a double-blind, placebo-controlled trial, meloxicam (7.5 or 15 mg) caused less endoscopically detected gastrointestinal (GI) damage (Lanza scale) than piroxicam 20 mg. The MELISSA study, a double-blind, randomized, 28-day trial in over 9,000 patients showed that meloxicam 7.5 mg caused statistically less total GI toxicity, dyspepsia, abdominal pain, nausea and vomiting, and diarrhea than diclofenac 100 mg, despite equivalent reductions in pain on movement for each treatment. A global safety analysis of clinical trials, representing over 5,600 patients and comprising 170 and 1,100 patient-years of exposure for meloxicam 7.5 mg and 15 mg, respectively, showed that meloxicam caused less GI toxicity and fewer peptic ulcers and GI bleeds than naproxen, diclofenac, or piroxicam. The renal safety profile and incidence of liver function abnormalities with meloxicam is equivalent to other NSAIDs available for clinical use. In conclusion, relatively selective COX-2 inhibition exemplified by meloxicam may offer effective symptom relief with an improved GI tolerability profile.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Guinea Pigs; Humans; Isoenzymes; Kidney Diseases; Meloxicam; Membrane Proteins; Mice; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles

Meloxicam is a new once daily non-steroidal anti-inflammatory drug (NSAID). Double-blind trials in over 5000 patients with osteoarthritis and rheumatoid arthritis have shown that meloxicam 7.5 mg and 15 mg are significantly more effective than placebo and comparable in efficacy to standard NSAIDs such as naproxen 750-1000 mg, piroxicam 20 mg and diclofenac 100 mg slow release. In a global safety analysis, both meloxicam doses produced significantly fewer gastrointestinal (GI) side effects than the comparators (p < 0/05). Severe GI side effects, discontinuations due to GI side effects and less serious events such as dyspepsia and abdominal pain were also significantly less frequent with meloxicam. Perforations, ulcerations and bleedings occurred in 0.1%, 0.2%, 1.2%, 0.6% and 2.1% of meloxicam 7.5 mg, 15 mg, piroxicam, diclofenac and naproxen patients respectively (p < 0.05 for piroxicam and naproxen compared with meloxicam). This improved safety profile is likely to be due to meloxicam's selective inhibition of COX-2 relative to COX-1.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Kidney Diseases; Male; Meloxicam; Osteoarthritis; Randomized Controlled Trials as Topic; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the treatment of rheumatoid arthritis and osteoarthritis. It has greater in vitro and in vivo inhibitory action against the inducible isoform of cyclo-oxygenase (COX-2), which is implicated in the inflammatory response, than against the constitutive form of this enzyme (COX-1), inhibition of which is associated with gastric, renal and other adverse effects. It has anti-inflammatory effects similar to or better than those of other NSAIDs in animal models, and a greater therapeutic ratio (ulcerogenic potential:efficacy in adjuvant arthritis). In healthy volunteers meloxicam 7.5 or 15 mg caused less gastrointestinal mucosal damage on endoscopy than piroxicam 20 mg, with a significant difference between meloxicam 7.5 mg and piroxicam. In comparative clinical trials, meloxicam was at least as effective as piroxicam and naproxen in patients with rheumatoid arthritis, and diclofenac and piroxicam in patients with osteoarthritis. Meloxicam was at least as well tolerated as piroxicam, diclofenac or naproxen overall but had improved gastrointestinal tolerability compared with these agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Availability; Clinical Trials as Topic; Half-Life; Humans; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

A need remains for the development of more effective therapies for the treatment of rheumatoid arthritis (both NSAIDs and DMARDs). The NSAIDs remain the cornerstone of symptomatic therapy, but concern remains about their safety, potential for the delay in commencing definitive therapy and theoretical pro-inflammatory effects. Each of the NSAIDs reviewed here do provide an advantage over therapies previously available and should prove to be useful additions to the rheumatologists' therapeutic armament.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; Cyclooxygenase Inhibitors; Cytokines; Digestive System; Drug Therapy, Combination; Humans; Indoles; Isoenzymes; Meloxicam; Misoprostol; Nabumetone; Oxindoles; Thiazines; Thiazoles

To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate (. A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of. After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biomarkers; Bone Remodeling; China; Female; Humans; Infusions, Intravenous; Male; Meloxicam; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Medronate; Thiazines; Thiazoles; Time Factors; Treatment Outcome; Young Adult

Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.. This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.. A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.. Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.. ClinicalTrials.gov identifier NCT00595517.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diclofenac; Esomeprazole; Female; gamma-Glutamyltransferase; Headache; Humans; Japan; Liver Function Tests; Male; Meloxicam; Middle Aged; Osteoarthritis; Peptic Ulcer; Phenylpropionates; Proton Pump Inhibitors; Secondary Prevention; Spasm; Thiazines; Thiazoles; Time Factors

To observe the clinical effect of Wenhua Juanbi Recipe (WJR) in treating rheumatoid arthritis (RA), its effects in reducing the dosage of Western medicine used and stabilizing condition of disease, as well as its influences on peripheral blood levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and anti-cyclic citrullinated peptide antibody (anti-CCP), for the sake of exploring its preliminary acting mechanism.. One hundred patients with RA were randomly assigned to 2 groups, the control group and the treated group, 50 in each group. All were treated with oral administration of methotrexate (MTX,7.5 mg per week), sulfasalazine (0.5 g, tid) and meloxicam (Mobic, 7.5 mg, bid), but to the treated group WJR was given additionally. The therapeutic course for both groups was 3 months. Clinical effect, changes of symptoms and physical signs, dosages of western medicines used, and laboratory indices in 2 groups after treatment were observed, and cases of relapse 3 months after treatment were figured out.. The total effective rate in the treated group was higher than that in the control group (88.0% vs 76.0%, P<0.05). The improvements in scores of symptoms and signs [joint pain (0.61 +/- 0.59), swelling (1.49 +/- 1.20), tenderness (0.90 +/- 0.69), movement (0.68 +/- 0.62), griping strength (68.56 +/- 6.50) mm Hg, morning stiff time (23.26 +/- 9.26) min], and in levels of laboratory indices (TNF-alpha, IL-1beta, anti-CCP, RF, ESR, CRP, PLT and Ig) in the treated group after treatment were significantly superior to those in the control group (P<0.05 or P<0.01). The dosages of MTX [(82.11 +/- 11.35) mg vs (94.75 +/- 10.23) mg] and meloxicam [(108.85 +/- 16.13) mg vs (189.63 +/- 18.44) mg] used, and the relapse rate in the treated group were lower significantly (P<0.05, P<0.01) than those in the control group respectively.. Effect of combined therapy of WJR and Western medicines is superior to that of using Western medicines alone in treating RA; WJR can reduce the dosages of Western medicines used and the relapse rate, as well as stabilize the condition of illness. It has the effects of immune regulating and anti-inflammatory reaction. Its mechanism for treating RA is possibly the inhibition on cytokines of TNF-alpha and IL-1beta.

Topics: Adult; Arthritis, Rheumatoid; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Interleukin-1beta; Male; Meloxicam; Methotrexate; Middle Aged; Phytotherapy; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha; Young Adult

To observe the clinical effect of bee-sting (venom) therapy in the treatment of rheumatoid arthritis (RA).. One hundred RA patients were randomly divided into medication (control) group and bee-venom group, with 50 cases in each. Patients of control group were treated with oral administration of Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7. 5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi-points and the above-mentioned Western medicines. Ashi-points were selected according to the position of RA and used as the main acupoints, supplemented with other acupoints according to syndrome differentiation. The treatment was given once every other day and all the treatments lasted for 3 months.. Compared with pre-treatment, scores of joint swelling degree, joint activity, pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking duration, morning stiff duration in bee-venom group and medication group were improved significantly (P<0.05, 0.01). Comparison between two groups showed that after the therapy, scores of joint swelling, pain and pressing pain, joint-swelling number and morning stiff duration, and the doses of the administered MTX and Mobic in bee-venom group were all significantly lower than those in medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was markedly higher than that in medication group (P<0.05). In addition, the relapse rate of bee-venom group was obviously lower than that of medication group (P<0.05; 12% vs 32%).. Combined application of bee-venom therapy and medication is superior to simple use of medication in relieving RA, and when bee-sting therapy used, the commonly-taken doses of western medicines may be reduced, and the relapse rate gets lower.

Topics: Acupuncture Points; Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Bee Venoms; Female; Humans; Male; Meloxicam; Methotrexate; Middle Aged; Recurrence; Sulfasalazine; Thiazines; Thiazoles

To perform a nonlinear mixed effect modelling (NONMEM) population pharmacokinetic analysis of meloxicam plasma concentrations in rheumatoid arthritis (RA) patients participating in three clinical trials, and to evaluate the effects of age, weight, gender and concomitant medications on meloxicam pharmacokinetics.. Meloxicam was administered to RA patients once daily for 3 weeks or 6 months at doses between 7.5 and 60 mg. Plasma samples were obtained at least 7 days after the first dose and meloxicam plasma concentrations were quantified by h.p.l.c.. NONMEM analysis was conducted on plasma samples derived from 586 patients. A one-compartmental model was found to describe the data adequately. For a typical subject in the population, a clearance of 0.377 l h-1 (95% confidence interval (CI) 0.0304-0.449) in males and 0.347 l h-1 (95% CI 0.274-0.419) in females was obtained. The volume of distribution was estimated to be 14.9 l. The findings were corroborated by subsequent analysis using WinBUGS. Analysis of covariates showed that age and gender both significantly (P < 0.005) affected clearance. The effect of age was relatively small and a dose adjustment of <10% was deemed unnecessary. Differences between males and females were attributed to differences in weight. No clinically relevant drug-drug interactions were found, although sulphasalazine and glucocorticoids both significantly (P < 0.005) affected meloxicam clearance (+19% and - 12%, respectively). The mechanisms by which these agents affect meloxicam clearance remain to be elucidated.. The population pharmacokinetic meloxicam data from patients with RA gave similar results to those obtained from phase I trials. However, uncommon drug interactions may not be detected in phase I trials because of the small number of observations made.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Thiazines; Thiazoles

This Phase III, placebo and active controlled, multicenter trial evaluated the efficacy and safety of meloxicam 7.5, 15, and 22.5 mg daily for the treatment of rheumatoid arthritis (RA).. A 12 week, randomized, double blind, double dummy, parallel group trial compared daily oral meloxicam 7.5, 15, and 22.5 mg to placebo (negative control) and diclofenac 75 mg BID (positive control). A total of 894 patients (18 years of age with confirmed RA who flared following an NSAID-free period) were randomized to be treated. Baseline scores for all endpoints were similar among the treatment groups. Patient assessments were at 0, 2, 4, 8, and 12 weeks or early termination.. All treatment groups demonstrated significant improvement from baseline (p < 0.001). Meloxicam 7.5 and 22.5 mg was significantly superior to placebo in all 5 primary efficacy endpoints (swollen joint count, tender joint count, patient pain, patient and physician global; all p < 0.05). Diclofenac 150 mg was superior to placebo for 4 of 5 primary efficacy measures (all but swollen joint count; p < 0.05) and meloxicam 15 mg was superior for 3 of 5 primary endpoints (patient pain and patient and physician global). AUC of patient global, patient pain, and modified Health Assessment Questionnaire demonstrated dose-response (p < 0.04), while AUC ACR20 showed a qualitative trend in the same direction. The rate of gastrointestinal (GI) events during the 12 week trial for all doses of meloxicam and diclofenac did not differ significantly from placebo (23.2-32.0%). GI withdrawals were comparable and not significantly different across all treatment groups (4.3-5.7%).. This trial demonstrated a dose response relationship for meloxicam 7.5, 15, and 22.5 mg using AUC measurement of response for the treatment of RA. All 3 doses of meloxicam. and positive control, were effective in the treatment of RA. The overall incidence rate of GI events did not differ significantly from placebo in either the meloxicam treatment groups or the positive control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Diclofenac; Double-Blind Method; Female; Humans; Isoenzymes; Liver Function Tests; Male; Meloxicam; Membrane Proteins; Middle Aged; Placebos; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles; Treatment Outcome

Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs (nabumetone) has been demonstrated to spare platelet function partially.. To compare the effects of the COX-2-selective inhibitor, meloxicam, with those of the non-selective NSAID, naproxen, on platelet function and thromboxane levels in RA patients.. In this randomized, controlled, cross-over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid, each during a 2-week period. Washout periods were applied. Before and after each 2-week period of NSAID intake, laboratory studies were performed.. Platelet aggregation was significantly less influenced, thromboxane levels were less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests during meloxicam exposure were comparable with baseline values.. In RA patients, meloxicam, a representative of the selective COX-2 inhibitors, does not interfere with platelet function and thromboxane levels, in contrast with naproxen (a non-selective COX inhibitor).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Bleeding Time; Blood Platelets; Cross-Over Studies; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Male; Meloxicam; Middle Aged; Naproxen; Platelet Aggregation; Random Allocation; Thiazines; Thiazoles; Thromboxane B2

This double-blind, double-dummy, two-way comparative trial evaluated the overall efficacy and tolerability of intramuscular (im) vs oral meloxicam.. 346 patients with rheumatoid arthritis (RA).. 173 patients in each group were randomised to receive either im meloxicam (15 mg) plus a placebo tablet, or oral meloxicam (15 mg) plus a placebo injection for 7 days.. Significant (p < 0.001) improvements in overall pain and disease activity were observed by patients treated with im and oral meloxicam, with no significant difference between treatments. The im formulation was better than the oral tablet in terms of rapidity of action (p=0.012), global efficacy (p=0.030) and duration of morning stiffness (p=0.026). Local tolerability of im meloxicam was very good and comparable with placebo injections.. Oral and im meloxicam (15 mg) were both effective and well-tolerated for acute exacerbations of RA. The im formulation had some advantages, such as a faster onset of action.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Meloxicam; Middle Aged; Thiazines; Thiazoles

This double-blind, randomised trial compared the efficacy and safety of meloxicam vs piroxicam in patients with soft-tissue rheumatism of the shoulder.. 599 outpatients at 88 centres in 9 countries.. Oral meloxicam 7.5 mg, meloxicam 15 mg or piroxicam 20 mg, once-daily for 14 days. The primary efficacy endpoint was the assessment of pain on day 7 relative to day 1.. Once-daily treatment with meloxicam 7.5 or 15 mg was comparable to piroxicam. A significantly higher proportion of meloxicam-treated patients had pain relief within day 1 or day 3. The incidence and intensity of adverse events was comparable between the treatment groups, although fewer patients in the meloxicam groups withdrew due to adverse events. There were no apparent differences between the two meloxicam doses.. Treatment with meloxicam was at least as effective as treatment with piroxicam, with a favourable global tolerability for both doses of meloxicam.

Topics: Acute Disease; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Piroxicam; Shoulder Pain; Thiazines; Thiazoles

To evaluate the efficacy and safety of meloxicam, a new acidic enolic nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in patients with rheumatoid arthritis (RA).. Meloxicam 15 and 7.5 mg daily was administered for 21 days in this double blind, randomized, placebo controlled study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and 147 received placebo.. Meloxicam 15 mg once daily was significantly superior (p < 0.05) to placebo in 3 of the 4 primary endpoints (disease activity assessed by the investigator, disease activity assessed by the patient, and reduction of the number of tender/painful joints). No difference was observed regarding number of swollen joints. The difference between meloxicam 7.5 mg once daily and placebo reached statistical significance in 2 of the 4 primary endpoints, disease activity assessed by the patient and number of tender/painful joints. A statistically significant difference between meloxicam 1.5 mg and 7.5 mg was not observed for any primary endpoint. The rating of global tolerance by investigators and patients at the end of the study was similar in the 3 treatment groups, indicating that meloxicam and placebo were generally similarly well tolerated. However, there was a slightly higher incidence of gastrointestinal (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5 mg, and meloxicam 15 mg groups, respectively. None were serious.. Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and symptoms of RA.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Demography; Double-Blind Method; Female; Humans; Joints; Male; Meloxicam; Middle Aged; Pain; Safety; Thiazines; Thiazoles; Treatment Outcome

To investigate the pharmacokinetic interaction of oral meloxicam with intravenous (i.v.) methotrexate (MTX) in patients with rheumatoid arthritis (RA).. Thirteen patients with RA received MTX 15 mg i.v. in the absence of nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of steady state levels of meloxicam. Plasma concentrations of MTX and meloxicam were determined using validated high performance liquid chromatography methods. One patient did not complete the study. The interaction of meloxicam and MTX was examined by equivalence testing. The endpoints AUCMTX, VssMTX, CltotMTX, and CmaxMTX were analyzed parametrically, whereas endpoints MRTMTX, CltotMTX, t1/2MTX, and tmaxMTX were analyzed nonparametrically.. The MTX plasma concentrations over time, with and without meloxicam, did not differ significantly. The point estimator for the ratio of log transformed data of the primary endpoint AUCMTX was 108%; the lower 95% confidence limit was 100% and the upper 95% confidence limit was 117%. Clinical laboratory values and adverse events revealed no increased MTX toxicity during concomitant treatment with meloxicam.. In this short term interaction study there was no statistically significantly effect of meloxicam on the pharmacokinetics of MTX. The combination of MTX and meloxicam did not lead to increased MTX toxicity.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Interactions; Female; Humans; Male; Meloxicam; Methotrexate; Middle Aged; Thiazines; Thiazoles

A multicentre, double-blind, randomized study was conducted in patients with rheumatoid arthritis (RA) in order to compare the efficacy and safety of two different doses of meloxicam, a new preferential cyclooxygenase-2 (COX-2) inhibitor. Four hundred and twenty-three patients were randomized to receive once-daily oral meloxicam 7.5 mg (n = 216) or meloxicam 15 mg (n = 207) for 3 weeks. The Ritchie joint index and pain in the morning were significantly improved versus baseline (P < 0.001) in both groups. There were no significant differences between the effects of each dose with respect to these measures nor with respect to final assessment of global efficacy by the patients. However, the 15 mg dose was associated with a significantly (P < 0.05) better effect on morning stiffness and grip strength. No differences between the doses were observed with regard to the other secondary efficacy parameter (pain at night, body weight and erythrocyte sedimentation rate). Both doses of meloxicam were well tolerated. There were no differences between the doses with respect to global tolerance as assessed by the patient and the patients, 'general condition'. In conclusion, meloxicam at a once-daily dose of either 7.5 or 15 mg is well tolerated and effective in the treatment of patients with RA.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Meloxicam; Middle Aged; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Drug Tolerance; Gastrointestinal Diseases; Humans; Meloxicam; Middle Aged; Naproxen; Thiazines; Thiazoles; Time Factors; Treatment Outcome

This multicentre, randomized, open controlled study compared the local and overall tolerability of i.m. meloxicam with i.m. piroxicam in 211 patients with rheumatoid arthritis (RA) (n = 95) or osteoarthritis (OA) (n = 116). Of these, 210 patients were randomized (2:1) to receive meloxicam 15 mg (n = 144) or piroxicam 20 mg (n = 66) for 7 days. Local tolerability of meloxicam was significantly better than piroxicam with respect to occurrence of redness after the first injection (P = 0.03) and global assessment after the first and final injections (P < 0.05). No rise in creatinine phosphokinase levels (a marker of muscle fibre damage) was observed with meloxicam, in contrast to piroxicam (P = 0.0001). The overall tolerability of both treatments was good. Significant differences in favour of meloxicam were observed for global efficacy assessed by the patient in RA (P < 0.05) and for overall pain intensity in OA patients (P = 0.02). In conclusion, i.m. meloxicam is safe and effective for the treatment of acute rheumatic pain and shows some superiority over piroxicam.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Injections, Intramuscular; Male; Meloxicam; Middle Aged; Osteoarthritis; Piroxicam; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period. The median estimated creatinine clearance and N-acetyl-beta-glucosaminidase/creatinine ratios (a marker of renal tubular damage) recorded at day 14, day 28 or 4-7 days after meloxicam treatment was terminated, were not statistically significantly different from baseline values. There was no evidence of accumulation of meloxicam. Overall, meloxicam was well tolerated. The most common adverse events were GI complaints of abdominal pain and dyspepsia. No adverse events related to the urinary system, or increases in serum urea or potassium were recorded. The results suggest that meloxicam, 15 mg once daily, does not further compromise renal function or result in accumulation of meloxicam over this treatment period in patients with pre-existing mild renal impairment.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Kidney Diseases; Male; Meloxicam; Middle Aged; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

Pain syndromes, acute and chronic, against the background of inflammatory diseases (such as osteoarthritis (OA)), degenerative-dystrophic changes (involutive process, trauma) or systemic diseases (rheumatoid arthritis, etc.) dictate a steady increase in the intake of nonsteroidal anti-inflammatory drugs (NSAIDs). The choice of the most «safe NSAID» is based on the assessment of the toxicity index (the ratio when blocking cyclooxygenase (COX)) and the development of relative risks (the benefit/risk ratio). As well as those adverse events that can be detected with individual sensitivity to a specific NSAIDs, taking into account the anamnesis of previous diseases and intolerance to NSAIDs, existing chronic diseases (gastrointestinal tract, cardiovascular system, type 2 diabetes mellitus), limiting the appointment of NSAIDs. Considering these circumstances, the NSAID meloxicam (Amelotex) can be recommended for the treatment of various genesis pain syndromes. A number of studies have demonstrated the efficacy and safety of meloxicam with different methods of its administration (per oral (p/o), intramuscularly (i/m)) in the treatment of pain syndrome in the lower back, with OA, etc. Recent studies concern intravenous (i/v) meloxicam (30 mg) administration with moderate and severe postoperative pain syndrome. Today, the most commonly pain therapy scheme using meloxicam includes step-by-step administration of injectable and oral forms: meloxicam i/m (1.5 ml) for 3-5 days, followed by a transition to p/o (7.5-15 mg) intake for 14 days, or complex therapy with meloxicam (Amelotex), with muscle relaxant and B vitamins.. Болевые синдромы, острые и хронические, на фоне воспалительных (таких как остеоартрит (ОА)), дегенеративно-дистрофических изменений (инволютивный процесс, травма) или системных заболеваний (ревматоидный артрит и др.) диктуют неуклонный рост приема нестероидных противовоспалительных препаратов (НПВП). Выбор наиболее безопасного НПВП основан на оценке показателей токсичности (соотношение при блокировании циклооксигеназы — ЦОГ), относительных рисков (соотношение польза/риск), а также нежелательных явлений (НЯ), обусловленных индивидуальной чувствительностью к конкретному НПВП. Для лечения пациентов с болевыми синдромами различного генеза широко используется мелоксикам (Амелотекс). В ряде исследований были продемонстрированы эффективность и безопасность мелоксикама при разных способах его назначения при лечении боли в нижней части спины, при ОА и др. Последние исследования касаются внутривенного введения мелоксикама (30 мг) при умеренном и выраженном послеоперационном болевом синдроме. Сегодня наиболее часто применяется схема терапии боли с последовательным назначением инъекционной и пероральной (п/о) форм мелоксикама — внутримышечно по 1,5 мл (15 мг) в течение 3—5 дней с последующим переходом на п/о прием (7,5—15 мг) в течение 14 дней и комплексная терапия мелоксикамом (Амелотекс), миорелаксантом, витаминами группы B.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diabetes Mellitus, Type 2; Humans; Meloxicam; Osteoarthritis

There are still debates on the association of increased cardiovascular risk with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) because of inconsistent results. Therefore, our study aims to evaluate the transient effects of selective and nonselective NSAIDs on the risk of stroke and acute myocardial infarction (AMI) in patients with RA. We conducted a case-crossover study of 5,921 stroke or AMI patients with co-morbidity of RA. All cases were identified from the Taiwan National Health Insurance Database between January 1, 2006, and December 31, 2011, according to the International Classification of Diseases, 9th Revision and Clinical Modification diagnosis codes from inpatient claims. The index date was defined as the date of hospitalization for stroke or AMI. Exposure to NSAIDs was compared during a case period (1 to 30 days before the index date) with a control period (91 to 120 days before the index date). The adjusted odds ratios (ORs) of stroke and AMI were estimated using conditional logistic regression models. Our results showed that overall NSAIDs use increased the risk of stroke by 1.40-fold (95% confidence interval [CI] 1.25 to 1.56) and risk of AMI by 1.73-fold (95% CI 1.29 to 2.32). After classifying NSAIDs into selective and nonselective groups, only nonselective NSAIDs use significantly increased the risks of stroke (adjusted OR 1.39; 95% CI 1.25 to 1.55) and AMI (adjusted OR 1.82; 95% CI 1.37 to 2.41), respectively. In conclusion, nonselective NSAIDs were associated with an increased risk of both stroke and AMI in patients with RA.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Diclofenac; Female; Humans; Ibuprofen; Logistic Models; Male; Mefenamic Acid; Meloxicam; Middle Aged; Myocardial Infarction; Odds Ratio; Risk Factors; Stroke

We investigated whether the concomitant use of meloxicam and methotrexate might induce kidney and liver damages in patients with rheumatoid arthritis (RA). We enrolled 101 RA patients with normal kidney and liver functions taking meloxicam and methotrexate concomitantly for more than 6 months. Blood and urine tests were performed. Estimated glomerular filtration rate (eGFR) and liver stiffness measurement (LSM) were used for evaluating silent kidney and liver damages. Ultrasonography was also performed to exclude structural abnormalities. We adopted 90 mL/min/1.73 mm(2) and 5.3 kPa as the cutoff for an abnormal eGFR and LSM. The mean age (85 women) was 51.9 years. The mean eGFR was 97.0 mL/min/1.73 m(2) and the mean LSM was 4.7 kPa. The mean weekly dose of methotrexate was 13.4 mg. The mean weekly dose of methotrexate did not correlate with eGFR or LSM. Neither the cumulative dose of meloxicam or methotrexate nor the mean weekly dose of methotrexate showed the significant odds ratio or relative risk for abnormal eGFR and LSM values. The use of higher-dose MTX, above 15 mg per week, with meloxicam did not significantly increase the risk for abnormal LSM and eGFR (RR = 2.042, p = 0.185; RR = 0.473, p = 0.218). The concomitant use of meloxicam and MTX did not clearly increase the risk of silent kidney or liver damage in RA patients with normal laboratory results taking MTX and meloxicam concurrently for over 6 months.

Topics: Acute Kidney Injury; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Asymptomatic Diseases; Chemical and Drug Induced Liver Injury; Cohort Studies; Drug Therapy, Combination; Elasticity Imaging Techniques; Female; Humans; Liver; Male; Meloxicam; Methotrexate; Middle Aged; Odds Ratio; Prospective Studies; Thiazines; Thiazoles

Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestinal (GI) and cardiovascular (CV) side effects. In this paper, the oral NSAID use of 143 patients with rheumatoid arthritis was assessed focusing on safety and farmacoeconomic aspects in a cross sectional non interventional study. The most widely used NSAIDs were meloxicam (n = 55, 38.5%) and diclofenac (n = 30, 21%). We found that coxibs were overused (n = 13, 9.1%) compared with the average total coxib consumption in Hungary. According to our results, drugs associated with GI friend side effect profile (meloxicam, celecoxib, etoricoxib) were much preferred in patients with previous GI events, than in patients with low GI risk. The previous occurrence of GI events were significantly higher (p = 0.019) in patients currently treated with safer NSAIDs, probably because of the so-called 'indication bias'. No statistically significant difference in patient's quality of life could be proved between NSAID drug groups. The uses of NSAIDs were considered to be rational concerning CV and GI risk as well as cost-effectiveness.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cross-Sectional Studies; Cyclooxygenase 2 Inhibitors; Diclofenac; Gastrointestinal Diseases; Humans; Hungary; Meloxicam; Thiazines; Thiazoles

In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system.. The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia.. Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%.. Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.

Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Protocols; Colombia; Diagnostic Services; Direct Service Costs; Disease Management; Drug Costs; Drug Therapy, Combination; Etanercept; Health Care Costs; Hospital Costs; Hospitals, University; Humans; Hydroxychloroquine; Immunoglobulin G; Infliximab; Isoxazoles; Leflunomide; Meloxicam; Methotrexate; Receptors, Tumor Necrosis Factor; Sulfasalazine; Thiazines; Thiazoles

Chronic arthritis adversely affects glomerular function and nonsteroidal anti-inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition, both acute and chronic inflammations may alter clearance of drugs. We studied (a) the effects of inflammation on the renal function and pharmacokinetics of rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced electrolytes excretion changes observed with NSAIDs; and (c) the influence of inflammation on distribution of these drugs into the kidney. Single oral doses of rofecoxib (10 mg kg(-1)), meloxicam (3 mg kg(-1)) or placebo were administered to normal or pre-adjuvant arthritic rats. Blood and urine samples were collected for the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were increased starting on day 9 in the groups with inflammation. Sodium and potassium excretion rates were not affected by inflammation. Meloxicam did not alter the electrolyte excretion in any of the groups. Rofecoxib significantly decreased sodium and potassium excretion in normal rats and potassium excretion in inflamed rats. Inflammation significantly increased plasma concentrations of rofecoxib, but not meloxicam. The ratios of the kidney:plasma concentrations were not significantly altered by inflammation following either drug. Inflammation altered kidney function, demonstrated by increases in BUN and plasma creatinine. However, it did not influence the urinary electrolytes excretion. Since we have observed similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory conditions, one may conclude that inflammation does not exacerbate the adverse effect.

Topics: Administration, Oral; Animals; Area Under Curve; Arthritis, Experimental; Arthritis, Rheumatoid; Cyclooxygenase 2 Inhibitors; Kidney; Kidney Function Tests; Lactones; Male; Meloxicam; Rats; Rats, Sprague-Dawley; Sulfones; Thiazines; Thiazoles

The study was to screen the possible risk factors of adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Shanghai patients with arthropathy.. The subjects were randomly selected from a database of outpatients with arthropathy from 9 main hospitals in Shanghai. A door to door retrospective epidemiological survey was used to collect demographic information about the patients, both individual and familial. This included data on their medical histories, lifestyle and dietary habits, history of smoking and alcohol consumption, history of drug therapy, quality of life (QOL) prior to NSAIDs intake, history of NSAIDs therapy and its ADR events, etc. Descriptive statistical methods and univariate analysis were also used to identify possible risk factors for ADRs induced by NSAIDs.. Of the 1002 patients surveyed, the average length of NSAIDs intake was 2 years. ADR incidence from different NSAIDs was high, in a range from 46.7 %-66.2 %. In general, the candidate risk factors for ADRs were different for each NSAID. Each of the candidate risk factors were defined and studied in order to evaluate its role in the determination of ADRs from NSAIDs. "Family history of ADRs caused by NSAIDs" was found to be a significant risk factor for the four commonly used NSAIDs: meloxicam, diclofenac, nimesulide, and nabumetone.. A retrospective epidemiological survey was useful in detecting the risk factors for ADRs caused by NSAIDs. The study found that different NSAIDs might have different risk factors and that there is no single risk factor universally applicable to all NSAIDs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; Child; Diclofenac; Dizziness; Exanthema; Female; Gastrointestinal Hemorrhage; Humans; Male; Meloxicam; Middle Aged; Nabumetone; Osteoarthritis; Retrospective Studies; Risk Factors; Spondylitis, Ankylosing; Stomach Diseases; Thiazines; Thiazoles

Celecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors, and were developed to minimize the risk of gastrointestinal (GI) toxicity commonly associated with non-steroidal anti-inflammatory drugs (NSAIDs). The Drug Safety Research Unit (DSRU) monitored the safety of these drugs immediately after launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between celecoxib and meloxicam during use in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and celecoxib (May to December 2000). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RR) obtained using regression modelling.. For celecoxib and meloxicam, respectively, 1054 (6.0%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events whereas 42 (0.2%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A higher proportion of the celecoxib cohort had an indication for osteoarthritis (28.1 vs 23.2%), were female (68.3 vs 67.1%), were aged 60 yr or more (59.5 vs 55.0%), were prescribed NSAIDs within 3 months of starting treatment (49.4 vs 47.9%), and had a past medical history of upper GI conditions (54.7 vs 29.2%) than those prescribed meloxicam. This suggests differential channelling of groups at higher risk of such events on to celecoxib compared with meloxicam. There was no difference between the two drugs in the time to occurrence of either group of event. The RR over the 270-day study period for celecoxib compared with meloxicam were 0.77 (95% CI 0.69, 0.85) and 0.56 (95% CI 0.32, 0.96) for symptomatic (acid/peptic) upper GI events and complicated upper GI conditions (perforations/bleeding), respectively, adjusted for age, age2, sex, indication, medical history of upper GI problems and whether NSAIDs were prescribed within 3 months prior to starting treatment.. This study reports a relative reduction (23%) in the incidence of symptomatic (acid/peptic) GI events, and a relative reduction (44%) in the incidence rate of complicated upper GI conditions (perforations/bleeding) for celecoxib compared with meloxicam.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Gastrointestinal Diseases; Humans; Incidence; Male; Meloxicam; Middle Aged; Osteoarthritis; Poisson Distribution; Pyrazoles; Regression Analysis; Retrospective Studies; Risk Factors; Sulfonamides; Thiazines; Thiazoles

Rofecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit (DSRU) monitored the post-marketing safety of these drugs in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM).. To compare the incidence rates of selected thromboembolic (TE)(cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed rofecoxib and meloxicam in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and rofecoxib (July to November 1999). Simple questionnaires requesting details of events recorded during/after treatment, indication and potential risk factors (including age, sex and NSAIDs prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event within each TE group were calculated; crude and age- and sex-adjusted rate ratios (RR) obtained using regression modelling.. During the 9 months after starting treatment, 21 (0.14%) and 19 (0.10%) patients were reported to have cardiovascular TE events, and 74 (0.48%) and 52 (0.27%) cerebrovascular TE events, and 6 (0.05%) and 20 (0.10%) were reported to have peripheral venous thrombotic events for rofecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from the start of treatment for both the cerebrovascular TE event group (log rank test P = 0.0063) and the peripheral venous thrombotic event group (log rank test P = 0.0264). Indication and use of a NSAID within 3 months prior to starting treatment had no statistically significant effect on the relative risk estimates of the event groups and was excluded from subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, for rofecoxib the adjusted cerebrovascular TE event group rate was higher than for meloxicam [RR 1.68 (95% CI 1.15, 2.46)]; lower than meloxicam for the peripheral venous thrombotic event group [RR 0.29 (95% CI 0.11, 0.78)], and not different for the cardiovascular TE event group [RR 1.38 (95% CI 0.71, 2.67)].. This study reports a relative increase in the rate of cerebrovascular TE events and a relative reduction in peripheral venous thrombotic events in users of rofecoxib compared with meloxicam. There was no difference in the rate of cardiovascular thromboembolic events. The incidence of these three groups of events reported in each of these two drug cohorts was low (less than 0.5%), therefore the relevance of our findings needs to be taken into consideration with other clinical and pharmacoepidemiological studies.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Chi-Square Distribution; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Humans; Incidence; Lactones; Male; Meloxicam; Middle Aged; Osteoarthritis; Risk Factors; Sulfones; Survival Analysis; Thiazines; Thiazoles; Thromboembolism

Celecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the post marketing safety of these drugs in England using the non-interventional observational cohort technique of Prescription-Event Monitoring (PEM).. To compare the incidence rates of selected thromboembolic (TE) (cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed celecoxib and meloxicam in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996-March 1997) and celecoxib (May and December 2000). Simple questionnaires requesting details of events occurring during/after treatment, indication and potential risk factors (including age, sex and whether NSAIDs had been prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RRs) were obtained using Poisson regression modelling.. During the 9 months after starting treatment, 28 (0.16%) and 19 (0.10%) of patients were reported to have experienced cardiovascular TE events, 68 (0.39%) and 52 (0.27%) cerebrovascular TE events, and 17 (0.10%) and 20 (0.10%) experienced peripheral venous thrombotic events for celecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from 30 days after the start of treatment for both the cardiovascular TE event group (log rank test P = 0.0153) and cerebrovascular TE event group (log rank test P = 0.0055). Indication and use of an NSAID within 3 months prior to starting treatment had no effect on the relative risk estimates of the event groups and was excluded in subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, the cerebrovascular TE event group rate was higher for celecoxib than for meloxicam, RR 1.66 (95% CI 1.10-2.51), over the study period and no different for the cardiovascular TE event group, RR 1.72 (95% CI 0.87-3.40) or peripheral venous thrombotic group, RR 1.06 (95% CI 0.51-2.19).. This study reports a relative increase in the rate of cerebrovascular TE events in users of celecoxib compared to meloxicam. There was no difference in the rate of cardiovascular TE events or peripheral venous thrombotic events between users of these two drugs. The incidence of these three groups of events reported in each of these two drug cohorts was low (<0.5%), therefore the relevance of our findings need to be taken into consideration with other clinical and pharmacoepidemiological studies.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Celecoxib; Cerebrovascular Disorders; Chi-Square Distribution; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Humans; Incidence; Male; Meloxicam; Middle Aged; Osteoarthritis; Peripheral Vascular Diseases; Pyrazoles; Risk Factors; Sulfonamides; Survival Analysis; Thiazines; Thiazoles; Thromboembolism

When new drugs with improved safety or efficacy are introduced, they may be preferentially prescribed to specific populations of patients. Safety and efficacy may be underestimated if such channelling effects are not recognized. Meloxicam and cyclooxygenase (COX)-2-specific inhibitors were developed as safer alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis and rheumatoid arthritis. Studies of the use of meloxicam and COX-2-specific inhibitors demonstrate that both of these drugs are being prescribed to patients at increased risk of gastrointestinal adverse drug events. In the case of COX-2-specific inhibitors, this channelling appears to represent a prescribing pattern consistent with current recommendations. Subsequent analysis of the data, after adjusting for channelling bias, showed that the risk of gastrointestinal toxicity for meloxicam was similar to that for other NSAIDs, while COX-2-specific inhibitors reduced the risk of developing gastrointestinal adverse drug events by approximately 60%. These studies serve as examples of observed channelling bias and highlight the need for adjusting for channelling in order to provide a valid assessment of relevant outcomes for drugs likely to be preferentially prescribed to specific populations.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Utilization; Female; Gastrointestinal Diseases; Humans; Isoenzymes; Male; Meloxicam; Membrane Proteins; Osteoarthritis; Prognosis; Prostaglandin-Endoperoxide Synthases; Risk Factors; Selection Bias; Thiazines; Thiazoles

Whereas there are numerous reported ocular side effects from systemic sulpha medication, most are rare and reversible, with myopia being the most common reaction observed. A case report is presented of sudden bilateral onset of -1.0 DS of myopia (from -3.0 to -4.0 DS) in a young adult female following the addition of a sulphonamide (sulphasalazine) to oral non-steroidal anti-inflammatory treatment (meloxicam) for rheumatoid arthritis. The myopia regressed to -3.50 DS after 2 weeks when all medication was withdrawn and stabilised at this level when subsequent treatment was resumed after 8 weeks with the non-steroidal anti-inflammatory drug celecoxib. The case indicates that account needs to be taken of the possibility that relatively modest myopic shifts encountered in young adult contact lens wearers may be associated with concomitant systemic medication.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Contact Lenses; Drug Therapy, Combination; Female; Humans; Meloxicam; Myopia; Sulfasalazine; Thiazines; Thiazoles; Visual Acuity

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Coronary Thrombosis; Cyclooxygenase Inhibitors; Humans; Meloxicam; Peptic Ulcer; Risk Factors; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Humans; Isoenzymes; Meloxicam; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Risk Factors; Thiazines; Thiazoles

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Humans; Meloxicam; Thiazines; Thiazoles

The aim of this study was to evaluate the anti-inflammatory effect of 4-hydroxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1, 2-benzothiazine-3-carboxamide-1,1-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with meloxicam in the presence or absence of interleukin-1beta. Meloxicam had no effect on both cyclooxygenase-1 and -2 expression as determined by Western blot analysis, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 activity, but only the higher doses of meloxicam inhibited cyclooxygenase-1 activity as determined by prostaglandin E(2) synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxygenase-1 on cultured rheumatoid synoviocytes without affecting cyclooxygenase expression. On the other hand, indomethacin had no selectivity and dexamethasone inhibited the expression of cyclooxygenase-2. Our data indicate that clinical efficacy and safety of meloxicam for rheumatoid arthritis may result from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-1 on rheumatoid synoviocytes.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blotting, Western; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dexamethasone; Dinoprostone; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Humans; Immunohistochemistry; Indomethacin; Isoenzymes; Meloxicam; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Synovial Membrane; Thiazines; Thiazoles

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Double-Blind Method; Humans; Isoenzymes; Meloxicam; Membrane Proteins; Peptic Ulcer; Prostaglandin-Endoperoxide Synthases; Randomized Controlled Trials as Topic; Risk Factors; Thiazines; Thiazoles

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID), which has a higher activity against cyclooxygenase-2 (COX-2) than against cyclooxygenase-1 (COX-1), with potentially high anti-inflammatory and analgesic action. This study was designed to assess the long-term safety and efficacy of meloxicam 15 mg daily. Three hundred and fifty-seven patients (aged 19-84 yr, mean 56 yr) with rheumatoid arthritis (RA) received meloxicam 15 mg orally once daily, for up to 18 months. Sixty-six per cent of patients remained on therapy for 18 months. Mean global efficacy, assessed by each patient on a visual analogue scale (0 cm = excellent, 10 cm = useless), was 3.32 +/- 3.1 cm at the last study visit (all patients included) and 2.33 +/- 2.25 cm after 18 months. Health status, general condition, morning stiffness, grip strength of right hand, Ritchie joint index, pain in the morning and pain at night all improved significantly. Efficacy was maintained through the study. Only 11.4% of patients discontinued prematurely due to lack of efficacy. Mean global tolerance was good. Twenty-eight per cent of patients experienced gastrointestinal (GI) adverse events, 21% musculoskeletal system disorders, 18% skin disorders and 15% respiratory disorders. Only 13.7% of patients discontinued due to adverse events. Severe GI effects, such as perforation, ulcer and bleeding, occurred in only three patients (0.8%). Withdrawals due to GI adverse events occurred in 3.9% of patients. Meloxicam 15 mg once daily was effective and compared favourably with standard NSAIDs regarding tolerance when administered to patients with RA over an 18 month period.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Meloxicam; Middle Aged; Thiazines; Thiazoles; Time Factors; Treatment Outcome

Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor for the treatment of rheumatic disease. This paper presents a global safety analysis of data from meloxicam clinical studies, focusing on gastrointestinal (GI) adverse events. Meloxicam 7.5 and 15 mg (n = 893 and 3282) were compared with piroxicam 20 mg (n = 906), diclofenac 100 mg slow release (n = 324) and naproxen 750-1000 mg (n = 243). With respect to all GI adverse events, meloxicam 7.5 and 15 mg were significantly better than all comparators in a pooled analysis of double-blind studies in rheumatoid arthritis (RA) and osteoarthritis (OA). When examining non-serious GI events, severe GI events, discontinuous due to GI events, dyspepsia, abdominal pain and upper GI events, both meloxicam doses were significantly better than comparator non-steroidal anti-inflammatory drugs (NSAIDs) in most cases. Where statistical significance was not demonstrated, there was generally a trend in favour of meloxicam. With respect to upper GI perforations, ulcerations and bleedings, the most serious of NSAID-associated side-effects, meloxicam was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen. Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutive COX-1.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Kidney Diseases; Male; Meloxicam; Middle Aged; Multicenter Studies as Topic; Osteoarthritis; Thiazines; Thiazoles