Rheumatoid Arthritis: Tugwell P

Blumenauer B, Coyle D, Tugwell P. · Faculty of Medicine, University of Ottawa, Ottawa, Canada. · Expert Opin Pharmacother. · Pubmed #11934345 No free full text.

Abstract: Rheumatoid arthritis affects ~ 1% of the population. It is associated with pain, deformity, decreased quality of life and disability that in turn affects patients' ability to work. A variety of disease-modifying antirheumatic drugs are available to control the disease activity of rheumatoid arthritis. The goal of treatment is to improve patients' quality of life and prevent joint destruction. This paper reviews both the clinical aspects of frequently prescribed disease-modifying antirheumatic drugs and the available cost-effectiveness information. Clinical evidence supports the effectiveness of methotrexate, etanercept, infliximab, gold, hydroxychloroquine, leflunomide, sulfasalazine, penicillamine, cyclosporin, azathioprine and corticosteroids. The last four of these are associated with greater toxicity and are only used if less toxic drugs are ineffective. The lack of published economic evaluations of disease-modifying antirheumatic drugs highlights the need for such studies to allow efficacious and cost-effective drugs to be used to prevent the long-term complications of uncontrolled rheumatoid arthritis.

Robinson V, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P. · Institute of Population Health, University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N-6N5. · Cochrane Database Syst Rev. · Pubmed #11869637 No free full text.

Abstract: BACKGROUND: Thermotherapy is often used as adjunct in the treatment of rheumatoid arthritis (RA) by rehabilitation specialists. OBJECTIVES: To evaluate the effectiveness of different thermotherapy applications on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: We searched Medline, EMBASE, Pedro, Current Contents, Sports Discus and CINAHL up to and including September 2001. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Hand searching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials, controlled clinical trials, cohort studies or case/control studies, of thermotherapy compared to control or active interventions in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search (VR, LB). These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Seven studies (n=328 subjects) met the inclusion criteria. The results of this systematic review of thermotherapy for RA found that there was no significant effect of hot and ice packs applications (Ivey 1994), cryotherapy (Rembe 1970) and faradic baths (Hawkes 1986) on objective measures of disease activity including joint swelling, pain, medication intake, range of motion (ROM), grip strength, hand function compared to a control (no treatment) or active therapy. There is no significant difference between wax and therapeutic ultrasound as well as between wax and faradic bath combined to ultrasound for all the outcomes measured after 1, 2 or 3 week(s) of treatment (Hawkes 1986). There was no difference in patient preference for all types of thermotherapy. No harmful effects of thermotherapy were reported. REVIEWER'S CONCLUSIONS: Superficial moist heat and cryotherapy can be used as a palliative therapy. Paraffin wax baths combined with exercises can be recommended for beneficial short term effects for arthritic hands. These conclusions are limited by methodological considerations such as the poor quality of trials.

Welch V, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P. · Clinical Epidemiology Unit, Ottawa Hospital - Civic Campus - F6, 1053 Carling Avenue, Ottawa, Ontario, Canada, K1Y-4E9. · Cochrane Database Syst Rev. · Pubmed #11406046 No free full text.

Abstract: BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% prefer heat therapy to no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients preferred thermotherapy to no therapy, thermotherapy can be used as a palliative therapy which can be applied at home as needed to relieve pain. These results are limited by the poor methodological quality of the trials.

Tugwell P, Welch V, Suarez-Almazor M, Shea B, Wells G. · Department of Medicine, Ottawa Hospital-General Campus, LM-12, 501 Smyth Road, Ottawa, Ontario, Canada. · Ann Rheum Dis. · Pubmed #11053083 links to  free full text

This publication has no abstract.

Welch V, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P. · Clinical Epidemiology Unit, Ottawa Hospital - Civic Campus - F6, 1053 Carling Avenue, Ottawa, Ontario, Canada, K1Y-4E9. · Cochrane Database Syst Rev. · Pubmed #11034770 No free full text.

Abstract: BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% like heat therapy better than no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients enjoy thermotherapy, and there are no harmful effects, thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain. There is no need for further research on the effects of heat or cold for RA.

Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas, USA, 77024. · Cochrane Database Syst Rev. · Pubmed #11034702 No free full text.

Abstract: OBJECTIVES: To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.

Suarez-Almazor ME, Belseck E, Shea B, Homik J, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024, USA. · Cochrane Database Syst Rev. · Pubmed #11034691 No free full text.

Abstract: OBJECTIVES: To assess the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0.52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.

Tugwell P. · Department of Medicine, University of Ottawa, Ontario, Canada. · Rheumatology (Oxford). · Pubmed #11001379 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease that results in progressive functional limitation, physical disability and premature death. RA extracts a considerable economic toll, particularly in terms of indirect costs related to lost productivity and premature mortality. Given these considerations, any therapy for RA that slows or prevents disability would be expected to confer economic benefit. Determination of drug efficacy does not automatically imply economic benefit, however. Establishment of economic benefit requires a rigorous analysis of both the benefits and the total costs of a given therapy The cost of drug therapy, including treatment of side-effects, currently constitutes only 15% of the total direct cost of RA, so it is important to assess other costs in any economic analysis. Common guidelines with regard to methods, units and data treatment are necessary to permit comparison of the economic benefit of different therapies within and across disease states. Such guidelines are being established for economic evaluations of medical interventions in RA. Application of these guidelines to future pharmacoeconomic studies of RA therapy will permit more accurate assessment of the economic benefit of such treatments. Given the current fiscal constraints on health care, demonstration of economic benefit will become an increasingly important factor for drug acceptance.

Brosseau L, Welch V, Wells G, deBie R, Gam A, Harman K, Morin M, Shea B, Tugwell P. · School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H-8M5. · Cochrane Database Syst Rev. · Pubmed #10796462 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about 10 years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the registries of the Cochrane Musculoskeletal group and the field of Rehabilitation and Related Therapies as well as the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, we selected only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently select trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: A total of 204 patients were included in the five placebo-controlled trials, with 112 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0. 8 to 1.7 cm). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference between the control and treatment hand, but all hands improved in terms of pain relief and disease activity. REVIEWER'S CONCLUSIONS: In summary, LLLT for RA is beneficial as a minimum of a four-week treatment with reductions in pain and morning stiffness. On the one hand, this meta-analysis found that pooled data gave some evidence of a clinical effect, but the outcomes were in conflict, and it must therefore be concluded that firm documentation of the application of LLLT in RA is not possible. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints.

Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024, USA. · Cochrane Database Syst Rev. · Pubmed #10796419 No free full text.

Abstract: OBJECTIVES: To estimate the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.

Wells G, Haguenauer D, Shea B, Suarez-Almazor ME, Welch VA, Tugwell P. · Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Room 3227, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #10796412 No free full text.

Abstract: OBJECTIVES: To estimate the short-term (up to one year) effects of cyclosporine for rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: All randomized clinical trials (RCTs) and controlled clinical trials (CCTs) comparing cyclosporine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Two reviewers determined the trials to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (DH, GW),and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. Methodological quality of the RCTs and CCTs was assessed by two reviewers (BS, DH). Rheumatoid arthritis outcome measures were extracted from the publications for change from baseline endpoints. Sufficient data were obtained to include in the pooled analysis the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). MAIN RESULTS: Three trials and 318 patients were included. A statistically significant decrease in the number of tender and swollen joints was observed for cyclosporine when compared to placebo. The standardized mean difference (SMD) for the change in the number of swollen joints was -0.969. Significant improvements in pain and the functional index were also found for cyclosporine. More side effects occurred in the cyclosporine group compared to placebo. REVIEWER'S CONCLUSIONS: Cyclosporine has an important clinical benefit int the short-term (up to one year) treatment of patients with progressive rheumatoid arthritis.

Suarez-Almazor ME, Belseck E, Shea B, Homik J, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024 USA. · Cochrane Database Syst Rev. · Pubmed #10796401 No free full text.

Abstract: OBJECTIVES: To estimate the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0. 52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.

Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024, USA. · Cochrane Database Syst Rev. · Pubmed #10796400 No free full text.

Abstract: OBJECTIVES: To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing sulfasalazine against placebo in patients with RA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the RCTs and CCTs independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Six trials, including 468 patients were included. A statistically significant benefit was observed for sulfasalazine when compared to placebo for tender and swollen joint scores, pain and ESR. The standardized weighted mean difference between treatment and placebo was -0.49 for tender and swollen joint scores, and -0.42 for pain. The difference for ESR was -17.6mm. Withdrawals from adverse reactions were significantly higher in the sulfasalazine group (OR=3.0). Patients receiving placebo were four times more likely to discontinue treatment because of lack of efficacy than patients receiving sulfasalazine. REVIEWER'S CONCLUSIONS: Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.

Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024, USA. · Cochrane Database Syst Rev. · Pubmed #10796399 No free full text.

Abstract: OBJECTIVES: To estimate the short-term efficacy and toxicity of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing MTX against placebo in patients with RA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the trials independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Five trials and 300 patients were included. A statistically significant benefit was observed for MTX when compared to placebo. Statistically significant differences were observed for all measures except ESR. The standardized weighted difference (effect size) between MTX and placebo for the various outcome measures varied between -0.43 and -1.5. No differences were observed in the total number of withdrawals and dropouts (OR = 0.95), although patients on MTX were three times more likely to discontinue treatment because of adverse reactions (OR=3.47) and four times less likely to withdraw due to lack of response (OR=0.22). REVIEWER'S CONCLUSIONS: Twenty-two percent of people on MTX withdrew due to adverse effects compared to seven percent of the placebo group. MTX has a substantial clinically and statistically significant benefit in the short term treatment of patients with RA.

Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P. · Sucre 3280, 7th Floor, Apt. 26, Buenos Aires, Argentina, 1428. · Cochrane Database Syst Rev. · Pubmed #10796393 No free full text.

Abstract: OBJECTIVES: To assess the effects of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) and haematologic side effects of low-dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and to determine whether or not folate supplementation alters MTX efficacy. SEARCH STRATEGY: We searched the Cochrane Controlled Clinical Trial's Register (CCTR), the Cochrane Musculoskeletal Group Specialized Register and Medline up to and including June 1999, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). We also handsearched the following: (i) bibliographic references; (ii) current contents of the last 6 months; (iii) abstracts of the rheumatology meetings; and (iv) all issues of four journals; Journal of Rheumatology, Arthritis & Rheumatism, Clinical and Experimental Rheumatology, and British Journal of Rheumatology. All languages were included. Principal investigators were also contacted in order to look for unpublished literature. SELECTION CRITERIA: We selected all double-blind, randomized, placebo-controlled, clinical trials (RCTs), in which adult RA patients were treated with a low dose of MTX (<20 mg / week) concurrently with folate supplementation. DATA COLLECTION AND ANALYSIS: Two observers extracted the data and assessed the quality of the trials. (BS, Z0) The overall treatment effect across trials was calculated using a fixed effect model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Results are presented with 95% Confidence Inervals (95% CI). Subgroup analyses were conducted evaluating different doses and sensitivity analysis looking at the quality of the trials. Publication bias was assessed with an inverted funnel plot technique. Heterogeneity of the trials was measured using a standard chi square test. Costs per month in different countries were compared. MAIN RESULTS: Of the 12 trials retrieved, 7 met the inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 80 patients with folinic acid and 67 patients with folic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but non-statistically significant reduction of 43% was found [OR = 0. 57 (95% CI 0.28 to 1.15)]. No major differences were observed between low and high doses of folic or folinic acid. Haematologic side effects could not be analyzed, since details of each haematologic side effect by patients were not provided. No consistent differences in disease activity parameters were observed when comparing placebo and folic or folinic acid at low or high doses, although patients on high dose folinic acid had an increase in the number of tender joints, but not swollen joints. Large differences in costs across countries were found, but folinic acid was more expensive in all. REVIEWER'S CONCLUSIONS: The results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems. We could not determine if folic was different from folinic acid. Therefore, for folinic acid to be considered cost-effective it must be found more effective than folic acid at reducing MTX side effects.

Clark P, Tugwell P, Bennet K, Bombardier C, Shea B, Wells G, Suarez-Almazor ME. · Health Services Research, Veterans Affairs Medical Center, Mailbox Station 152, 2002 Holcombe Blvd, Houston, Texas 77024, USA. · Cochrane Database Syst Rev. · Pubmed #10796386 No free full text.

Abstract: OBJECTIVES: To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included. DATA COLLECTION AND ANALYSIS: Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout. MAIN RESULTS: Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2). REVIEWER'S CONCLUSIONS: Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.

Ortiz Z, Shea B, Garcia Dieguez M, Boers M, Tugwell P, Boonen A, Wells G. · Academia Nacional de Medicina de Buenos Aires, Argentina. · J Rheumatol. · Pubmed #9918266 No free full text.

Abstract: To review the available evidence that has used generic instruments alone or in comparison with disease specific instruments. A systematic review was carried out using the methods recommended by the Cochrane Collaboration. We used MEDLINE and EMBASE searches and we performed a hand search of the abstracts listed under "quality of life" at American College of Rheumatology (ACR) meetings. Selection was limited to randomized controlled trials (RCT) using generic instruments in populations older than 18 years with any of the following diseases: rheumatoid arthritis, fibromyalgia, osteoporosis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis. Language was restricted to English papers. Studies using only disease-specific instruments were excluded. From 488 articles retrieved, 13 reports of 10 randomized controlled trials were selected. There were 101 abstracts on quality of life in ACR abstract books; 78 abstracts contained data on generic instruments, and of these, 9 described their use in RCT. Despite a substantial increase in the number of papers and abstracts addressing different aspects of generic questionnaires, the majority of the papers were descriptive. The evidence is not yet available to document that any of the generic instruments pass the requirements of the OMERACT Filter.

Osiri M, Deesomchok U, Tugwell P. · Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Pathumwan, Bangkok, 10330, Thailand. · Clin Rheumatol. · Pubmed #16365685 No free full text.

Abstract: The aim of this study was to compare the effectiveness of different disease-modifying anti-rheumatic drugs (DMARDs) in improving disease activity and functional status in patients with rheumatoid arthritis (RA). One hundred and fifty-two Thai RA patients treated with at least one DMARD were enrolled in this 1-year cohort. Demographic characteristics, baseline and end-of-study data on disease activity and Health Assessment Questionnaire (HAQ) Disability Index of the subjects were compared among different DMARD options. Predictors of HAQ score were investigated using regression analysis. The results showed that the studied patients had established RA with mild to moderate activity. More than 85% were prescribed methotrexate (MTX) as single or combined DMARDs. At 1 year, improvement in most activity measures was experienced. However, all patients had functional declines. Patients taking antimalarial agents had the maximal rate of functional deterioration. Patients taking MTX-based DMARDs had significantly lower rate of functional decline than patients taking DMARDs without MTX (p=0.018). Only patients receiving MTX-based DMARDs had clinically meaningful improvement in HAQ score. The predictors of HAQ score at 1 year included baseline HAQ score and patient global assessment at end of study. In conclusion, although DMARD treatment was shown to improve disease activity in RA patients, functional deterioration was evident in our cohort. Thus, measures of functional status are more appropriate than measures of disease activity to evaluate treatment effects of DMARDs in established RA in clinical practice. MTX-based DMARDs should be prescribed where possible in RA patients with persisting activity due to their ability to delay functional deterioration.

Brosseau L, Milne S, Wells G, Tugwell P, Robinson V, Casimiro L, Pelland L, Noel MJ, Davis J, Drouin H. · School of Rehabilitation Sciences, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #15517640 No free full text.

Abstract: OBJECTIVE: The objective of this metaanalysis is to examine the effectiveness of continuous passive motion (CPM) following total knee arthroplasty (TKA). METHODS: This metaanalysis used the methodology proposed by the Cochrane Collaboration. RESULTS: This review of 14 studies (952 patients) found significant improvements in active knee flexion and analgesic use 2 weeks postoperatively with the use of CPM and physiotherapy (PT) compared to PT alone. In addition, length of hospital stay and need for knee manipulations were significantly decreased in the CPM group. Not enough data were available to compare the degree of knee flexion applied or number of hours of application of CPM. However, significant results were not found for other comparisons such as short term CPM application versus longterm CPM application and wide treatment range versus small treatment range for the outcomes of active knee flexion, passive knee flexion and extension, presence of a fixed flexion deformity, use of analgesic, or total knee range of motion. CONCLUSION: CPM combined with PT may offer beneficial results for patients post-TKA. However, the potential benefits will need to be carefully weighed against the inconvenience and expense of CPM. More research is necessary to assess the differences in effectiveness with different characteristics of application such as total duration of treatment and intensity of CPM interventions.

Maetzel A, Strand V, Tugwell P, Wells G, Bombardier C. · Arthritis and Immune Disorder Research Centre, University Health Network, Toronto, Ontario, Canada. · Pharmacoeconomics. · Pubmed #11817993 No free full text.

Abstract: OBJECTIVE: To compare disease-related medical care and productivity costs, and utilities, in 482 patients with rheumatoid arthritis randomised to receive leflunomide, methotrexate or placebo during a 12-month period. DESIGN AND SETTING: Prospective pharmacoeconomic analysis of a 1-year randomised double-blind trial set in North America. PERSPECTIVE: Societal and the Ontario Ministry of Health. METHODS: Information on healthcare resources, out-of-pocket expenses, loss of working time and time spent on chores, related to the disease or the medication, were collected at 4-week intervals and at study discontinuation. Rating scale and standard gamble (SG) utilities (0 = worse; 100 = best) were collected at baseline and at 6 and 12 months or study exit. Medical care costs in Canadian dollars (Can dollars) were calculated using Ontario reimbursement schedules. US patients' expenses were converted to Can dollars using 1995 purchasing power parity. Lost wages were calculated by age and gender according to 1995 Canadian wage data. All costs were adjusted to 1999 Can dollars and arithmetic mean costs were compared using the nonparametric bootstrap. Analysis of covariance was performed to compare utilities between groups. RESULTS: Mean (standard deviation) rating scale values and SG utilities, respectively, for leflunomide, methotrexate and placebo were 67.7 (18.0), 64.8 (18.1) and 57.5 (9.2), and 80.2 (22.1), 83.2 (18.0) and 77.0 (20.5). Both leflunomide and methotrexate had higher rating scale values (p < 0.05) compared with placebo; SG utilities were significantly different between methotrexate and placebo (p < 0.05). Annualised total rheumatoid arthritisb- or drug-related costs for leflunomide, methotrexate and placebo, respectively, were Can dollars 1761, Can dollars 1280 and Can dollars 1324, and medical care costs were Can dollars 753, Can dollars 620 and Can dollars 167 (all costs exclude drug acquisition and monitoring costs). Annual drug acquisition/ routine monitoring costs were estimated, respectively, at Can dollars 3853/Can dollars 483 for leflunomide and Can dollars 258/Can dollars 599 for methotrexate. Differences between overall costs (excluding drug acquisition and monitoring costs) and medical care costs were not statistically significant. The costs of treating patients with leflunomide were significantly higher than for methotrexate when drug acquisition and monitoring costs were included (p < 0.0001). CONCLUSIONS: No statistically significant differences in utilities could be found between leflunomide or methotrexate. When drug monitoring and acquisition costs are excluded, leflunomide has an otherwise similar economic profile compared with methotrexate, the current gold standard. The acquisition cost of leflunomide is a driving factor in increasing the costs of therapy. These higher costs need to be assessed relative to the therapeutic value of leflunomide.

Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, Dorrier C, Thompson A. · Department of Medicine, Ottawa Hospital, Ontario, Canada. · Arthritis Rheum. · Pubmed #10728742 links to  free full text

Abstract: OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.

Strand V, Tugwell P, Bombardier C, Maetzel A, Crawford B, Dorrier C, Thompson A, Wells G. · University of Toronto, Ontario, Canada. · Arthritis Rheum. · Pubmed #10513801 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.

Wells G, Boers M, Shea B, Tugwell P, Westhovens R, Saurez-Almazor M, Buchbinder R. · University of Ottawa and Ottawa Hospital, Canada. · J Rheumatol. · Pubmed #9918267 No free full text.

Abstract: This is the initial report of the generic health OMERACT study concerned with the sensitivity to change of generic quality of life (QOL) measures. Our objective was to determine which QOL instrument is best able to show a statistically significant improvement in patients with rheumatoid arthritis (RA) demonstrating relevant improvement in a core set of disease activity and disease-specific disability measures. A multicenter controlled trial of a single group with repeated measurements at 0 (baseline), 3, and 6 months was conducted. All participating centers recruited 10 patients with RA who were about to start methotrexate therapy for the first time because of active disease. Assessments included disease activity measures, disease-specific disability measures, and generic QOL measures. To date, 40 patients have been recruited from 4 centers for the study. After 6 months of treatment many of the generic QOL measures showed a 20% improvement from baseline and medium standardized response means around 0.5. In particular, the Nottingham Health Profile (NHP) and the Rheumatoid Arthritis Quality of Life (RAQOL) measures had the largest percentage improvement (22 and 29%, respectively) and standardized response means (both with 0.54). Early results on the sensitivity of generic health QOL measures are promising, in particular for the NHP and RAQOL measures.

Li T, Wells G, Westhovens R, Tugwell P. · Global Health Outcomes, P.O. Box 4000, Mail stop J23-02, Bristol-Myers Squibb, Princeton, NJ 08543, USA. · Rheumatology (Oxford). · Pubmed #19141573 No free full text.

Abstract: OBJECTIVE: To examine the validity, reliability and sensitivity to change of the Activity Participation Questionnaire (APaQ), a simple measure of activity participation for patients with RA. METHODS: The questionnaire contained two items: (i) number of days in the past month of being unable to perform one's usual activities because of RA; and (ii) a score measuring how often one's usual activities could be completed. The APaQ was administered to 1043 RA patients in two clinical trials of abatacept. Construct validity was evaluated by examining changes from baseline in activity scores by clinical response measured by the European League Against Rheumatism (EULAR) and ACR criteria and minimal disease activity (MDA) state and by correlations with patient-reported outcome measures of physical function, disease activity, pain and fatigue at study end-point. Internal consistency, test-retest reliability and sensitivity to change were assessed. RESULTS: Both activity participation items were significantly associated with levels of EULAR and ACR response and the achievement of MDA state (P < 0.0005 for all comparisons). Moderate correlations with patient-reported outcomes were consistently found (correlations 0.5-0.6). Cronbach's alpha was 0.7 indicating good internal consistency, the intraclass correlation coefficient of 0.6 suggesting acceptable test-retest reliability. Sensitivity to change was demonstrated by the treatment differences and the standardized response mean (0.39 and 0.30) for the two activity items. CONCLUSION: The APaQ is a simple, reliable and valid measure of patient activity, which is sensitive to change, suggesting its suitability for use in clinical trials.

Tugwell P, Maxwell L, Welch V, Kristjansson E, Petticrew M, Wells G, Buchbinder R, Suarez-Almazor ME, Nowlan MA, Ueffing E, Khan M, Shea B, Tsikata S. · University of Ottawa, Ottawa, Ontario, Canada. · Arthritis Rheum. · Pubmed #18975366 No free full text.

Abstract: OBJECTIVE: To determine whether Cochrane Musculoskeletal Group (CMSG) systematic reviews and corresponding primary studies of rheumatoid arthritis interventions report and analyze the data needed to assess the effectiveness of interventions in reducing socioeconomic differences in health and/or improving the health of the poor. METHODS: We selected all CMSG reviews on rheumatoid arthritis published since issue 1, 2003. Fourteen reviews were identified; 147 of the 156 primary studies included in these reviews were obtained and assessed. We extracted data on whether the dimensions place of residence, race/ethnicity/culture, occupation, gender, religion, education, socioeconomic status, and social capital and networks (PROGRESS) were reported or analyzed, and whether any interventions were aimed at disadvantaged or low- and middle-income country populations. RESULTS: Among the dimensions of PROGRESS reported at baseline in 147 primary studies, gender (89%) was the most commonly reported, followed by education (25%) and race/ethnicity (18%). Less than 50% of the systematic reviews reported dimensions of PROGRESS even when they had been reported in the primary study. Of 147 primary studies, 6 (5%) were aimed specifically at disadvantaged populations; another 6 reported on effectiveness by at least 1 dimension of PROGRESS. CONCLUSION: Primary studies of interventions for rheumatoid arthritis generally reported few variables necessary to answer questions about health inequalities. Most CMSG systematic reviews failed to assess those variables even when described in the primary studies. The Cochrane Health Equity Field welcomes the opportunity to provide guidance to systematic review authors on incorporating equity considerations into their reviews.