Methotrexate for rheumatoid arthritis

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 Key experts in the area were contacted for further published and unpublished articles.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.