healon and Osteoarthritis--Knee

Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005.. To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors.. We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions.. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis.. We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, bene. Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

Topics: Adrenal Cortex Hormones; Arthralgia; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic; Therapeutic Irrigation

Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intraarticular (IA)) may relieve inflammation, and reduce pain and disability.. To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (to January (week 1) 2006 for update), EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched.. Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure.. Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk (RR).. Twenty-eight trials (1973 participants) comparing IA corticosteroid against placebo, against IA hyaluronan/hylan (HA products), against joint lavage, and against other IA corticosteroids, were included.IA corticosteroid was more effective than IA placebo for pain reduction (WMD -21.91; 95% confidence interval (CI) -29.93 to -13.89) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment. Data on function were sparse at one week post injection and neither statistically significant nor clinically important differences were detected. There was evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of evidence for efficacy in functional improvement. At four to 24 weeks post injection, there was lack of evidence of effect on pain and function (small studies showed benefits which did not reach statistical or clinical importance, i.e. less than 20% risk difference). For patient global, there were three studies which consistently showed lack of effect longer than one week post injection. However, all were fairly small sample sizes (less than 50 patients per group). This was supported by another study which did not find statistically significant differences, at any time point, on a continuous measure of patient global assessment (100 mm VAS).In comparisons of corticosteroids and HA products, no statistically significant differences were in general detected at one to four weeks post injection. Between five and 13 weeks post injection, HA products were more effective than corticosteroids for one or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. One study showed a difference in function between 14 to 26 weeks, but no differences in efficacy were detected at 45 to 52 weeks. In general, the onset of effect was similar with IA corticosteroids, but was less durable than with HA products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was superior to betamethasone for number of patients reporting pain reduction up to four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons between IA corticosteroid and joint lavage showed no differences in any of the efficacy or safety outcome measures.. The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.2 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.2. Future trials should have standardised outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage).

Topics: Adrenal Cortex Hormones; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Therapeutic Irrigation

To evaluate the efficacy and safety of injection of high molecular weight (HMW) hyaluronan (Orthovisc) in patients with mild, moderate, and severe knee osteoarthritis (OA).. A randomized, arthrocentesis-controlled, multicenter trial. Patients (n = 372) were randomized to 4 weekly HMW hyaluronan injections (O4, n = 128), 3 weekly HMW hyaluronan injections followed by one arthrocentesis (O3A1, n = 120), or 4 arthrocenteses without injection (control group, A4, n = 124). All patients had knee OA, as determined by Kellgren-Lawrence (K-L) grade, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score > or = 200 mm and < 400 mm in index knee and < 150 mm in contralateral knee. The primary outcome measure was the proportion of patients achieving a 20% relative and 50 mm absolute improvement from baseline in WOMAC pain score at Weeks 8, 12, 16, and 22 post-baseline in the index knee. Secondary outcomes were Patient Global score, Investigator Global score, and Pain on Standing score.. The evaluable subgroup consisted of patients with K-L grade 2 or 3 at baseline. The comparison of O4 versus A4 for the primary outcome approached, but did not reach, significance in the evaluable subgroup: 76% of O4 patients had > or = 20% improvement in WOMAC pain score at Week 8 compared to 62% of A4 patients. More O4 patients had > or = 40% improvement in WOMAC pain score compared to A4. The effectiveness of the 3-injection regimen (O3A1) was masked by a possible placebo effect from the needle injection procedure in the A4 (control) group. No differences between groups were observed with respect to incidence of adverse events.. Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee.

Topics: Adult; Antirheumatic Agents; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Severity of Illness Index; Treatment Outcome

To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA).. A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged >50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN >0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables.. Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (-33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (-0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively.. A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.

Topics: Aged; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Disease Progression; Double-Blind Method; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Prospective Studies; Severity of Illness Index; Treatment Outcome

A pilot study was designed to investigate the efficacy of two different hyaluronic acid preparations combined to physical therapy in patients with knee osteoarthritis in terms of reduction in pain and disability and muscle strengthening. Thirty-seven patients with symptomatic osteoarthritis of the knees were randomly assigned into three groups. First group received a lower molecular weight hyaluronic acid plus physical therapy, second group received a higher molecular weight hyaluronic acid plus physical therapy, and the third group received physical therapy alone. The isokinetic knee muscle strengths and index of severity for osteoarthritis of the knee scores were evaluated at baseline, at the end of treatment (3 weeks) and at 3 months of follow up. At both short-term (3 weeks) and long-term (3 months) evaluations, index of severity for osteoarthritis of the knee scores were reduced in all three groups, while there was no significant muscle strengthening.

Topics: Adjuvants, Immunologic; Adult; Aged; Female; Humans; Hyaluronic Acid; Injections, Intra-Arterial; Male; Middle Aged; Muscle, Skeletal; Osteoarthritis, Knee; Pain; Physical Therapy Modalities; Pilot Projects; Severity of Illness Index; Treatment Outcome

Intra-articular (IA) injection of hyaluronic acid (HA) (IA-HA) is a well-recognized treatment option for pain associated with symptomatic knee osteoarthritis (OA). IA-HA products differ in their HA content, molecular weight, cross-linking, and source of HA. These differences are assumed to affect the biocompatibility of the IA-HA products once injected inside the knee joint.. In the present study, we investigated the biocompatibility of three multiple-injection IA-HA products available in the global market. These included SUPARTZ FX™, a medium range molecular weight HA derived from rooster comb (Avian-HA); ORTHOVISC®, a high range molecular weight HA obtained through biological fermentation (Bio-HA); and SYNVISC®, a high molecular weight cross-linked hyaluronan derived from rooster comb (Avian-CL-HA). Rabbit knee joint tissues were histologically and biochemically examined after IA injection of the products. Furthermore, we compared the amounts of impurities in the IA-HA products.. IA injection of Avian-CL-HA into rabbit knee joints induced the aggregation of inflammatory cells, infiltration of eosinophils, and an increase in the number of cells in the synovial fluid. However, these effects were not seen in the Avian-HA and Bio-HA groups. The residual protein content and the contaminant levels of bacterial endotoxins were below the limit of quantitation in all HA products. Avian-CL-HA contained relatively a large amount of (1 → 3)-β-D-glucan, but this was below the lower limit of quantification in the other HA products.. The present results clearly demonstrate that the biocompatibility of Avian-HA is comparable to that of Bio-HA, and they were both considered to have a favorable safety profile for the treatment of symptomatic OA of the knee. However, immunostimulatory activity was observed after injection of Avian-CL-HA: this might be a result of its unique cross-linking structure and/or the considerable amount of (1 → 3)-β-D-glucan impurity present in the formulation.

Topics: Animals; Drug Contamination; Humans; Hyaluronic Acid; Injections, Intra-Articular; Knee Joint; Male; Materials Testing; Models, Animal; Osteoarthritis, Knee; Rabbits; Synovial Fluid; Viscosupplements

This study aims to compare the properties of currently available intra-articular hyaluronate (IA-HA) products widely available in the USA to those of healthy knee synovial fluid with respect to their bulk rheological properties. We hypothesize that products would have differing rheological properties, with some more closely resembling the properties and physiological aspects of healthy joint fluid HA.. We obtained reported HA product molecular weights, as well as measurements of the presence of cross-linking, zero shear rate viscosity, shear thinning ratio, and crossover frequency for the following IA-HA products available in the USA: Euflexxa. Differences were seen between the study products across all of the investigated parameters. Hyalgan, Supartz, Orthovisc, and Euflexxa had a linear chain structure, while Synvisc, Synvisc-One, and Monovisc were cross-linked in structure. Molecular weight, shear rates, and crossover frequencies ranged widely across tested products, with values ranging from below to above those reported for healthy knee synovial fluid HA. When compared to healthy knee parameter values reported within the current literature, observed parameters for Euflexxa and Orthovisc were typically seen to be the most similar to healthy knee synovial fluid. When comparing Euflexxa and Orthovisc directly, Euflexxa was more often similar to the properties of healthy knee synovial fluid with respect to the observed parameters of molecular structure, shear rates, and crossover frequency.. Available IA-HA products vary with respect to molecular weight, presence of cross-linking, shear rate dependency of viscosity, and crossover frequency. Since IA-HA treatment for osteoarthritis aims to restore synovial fluid back to original HA property characteristics, using HA supplements resembling healthy synovial fluid is a logical approach. Our findings demonstrate that Euflexxa is the most similar to healthy synovial fluid with respect to molecular structure, shear rates, and crossover frequency.. Ferring Pharmaceuticals, Inc.

Topics: Glycosaminoglycans; Humans; Hyaluronic Acid; Injections, Intra-Articular; Molecular Weight; Osteoarthritis, Knee; Rheology; Synovial Fluid; Viscosity; Viscosupplements