Rheumatoid Arthritis: Towheed T

Garner S, Fidan D, Frankish R, Judd M, Shea B, Towheed T, Wells G, Tugwell P. · Department of Public Health, St. George's Hospital Medical School, Cranmer Terrace, London, UK, SW17 0RE. · Cochrane Database Syst Rev. · Pubmed #12519610 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH STRATEGY: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. REVIEWER'S CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

Garner S, Fidan D, Frankish R, Judd M, Towheed T, Wells G, Tugwell P. · National Institute for Clinical Excellence, 11 Strand, London, UK, WC1N 5HR. · Cochrane Database Syst Rev. · Pubmed #12137705 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis. SELECTION CRITERIA: We included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0.44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.

Garner S, Fidan D, Frankish R, Judd M, Towheed T, Wells G, Tugwell P. · National Institute for Clinical Excellence, 11 Strand, London, UK, WC1N 5HR. · Cochrane Database Syst Rev. · Pubmed #12076502 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institue for Clincal Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inibitors for arthritis. SELECTION CRITERIA: Relevant studies were randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1995) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating the efficacy and toxicity of rofecoxib in RA were identified and met the criteria. One compared rofecoxib to placebo and the other compared rofecoxib to naproxen. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Patients taking rofecoxib had a greater risk of having a myocardial infarction (MI) than patients taking naproxen (RR 4.03, 95% CI, 2.86 to 5.68). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.

Towheed T, Shea B, Wells G, Hochberg M. · Medicine and of Community Health and Epidemiology, Queen's University, Etherington Hall-Room 2066, Kingston, Ontario, Canada, K7L 3N6. · Cochrane Database Syst Rev. · Pubmed #10796384 No free full text.

Abstract: OBJECTIVES: To review all randomized trials of analgesics and anti-inflammatory therapy in osteoarthritis (OA) of the hip. To determine which non-steroidal, anti-inflammatory drug (NSAID) is the most effective, and which NSAID is the most toxic. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register and Medline up to August 1994. Reference lists of all trials were also manually searched. SELECTION CRITERIA: All randomized controlled trials comparing non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics in patients with Osteoarthritis. The trials selected for inclusion were identified by one reviewer (TT) and rechecked by a second (MH). DATA COLLECTION AND ANALYSIS: Qualitative assessments were performed using a quality scoring system designed for NSAID trials in rheumatoid arthritis. Both the design and analysis aspects of the trials were evaluated, each aspect being rated on a scale of 0 to 8. A quantitative method, which calculates the ratio of improvement produced by one NSAID to that produced by another, was used to rate the relative efficacy of different NSAIDs with respect to pain relief. Toxicity comparisons were made according to the reviewer findings. All quality assessments were carried out independently by two reviewers (TT, BS). All data abstraction was carried out by one reviewer (TT) and rechecked by two other reviewers (BS, GW). A consensus was reached on discrepancies. MAIN RESULTS: Forty-three trials were identified, and of these, 39 evaluated NSAIDs, while four evaluated only analgesics. The median design and analysis scores were two and four respectively. Six NSAIDs were included in at least five trials. Of these, indomethacin was rated more effective in five of its seven comparisons, but more toxic in seven of 12 comparisons. Only five of the 29 (17%) NSAID comparisons found statistically significant differences in efficacy. Of the 43 RCTs identified only 17 had statistical data available for future pooling for this meta-analysis. In the case where data was missing, authors of the trials will be contacted for inclusion of data in future reviews. REVIEWER'S CONCLUSIONS: NSAID trials in patients with OA of the hip appear to be weakened by the lack of standardization of case definition of OA, and also by the lack of standardization of outcome assessments. No clear recommendations for the choice of specific NSAID therapy in hip OA can be offered at this time based on this analysis.