Comparison of Azathioprine, Methotrexate, and the Combination of the Two in the Treatment of Rheumatoid Arthritis. A Forty-Eight-Week Controlled Clinical Trial With Radiologic Outcome Assessment.

Publication Type
Journal Article
Year of Publication
1995
Authors
Willkens, RF; Sharp, JT; Stablein, D; Marks, C; Wortmann, R
Secondary
Arthritis Rheum
Volume
38
Start Page
1799
Pagination
1799-1806
Date Published
12/1995
Keywords
Antirheumatic Agents; Arthritis-Rheumatoid; Arthrography; Azathioprine; Blood Sedimentation; Cross-Over Studies; Double-Blind Method; Drug Therapy- Combination; Female; Male; Methotrexate; Prospective Studies; Treatment Outcome
Abstract

OBJECTIVE:

To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial.

METHODS:

Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5mg MTX/week plus 50 mg AZA/day-7.5 mg MTX/week plus 100 mg AZA/day), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks.

RESULTS:

One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation.

CONCLUSION:

This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX.

Comment in

Toxicity of combination therapies in rheumatoid arthritis: comment on the article by Willkens et al. [Arthritis Rheum. 1996]

Results of controlled study of combination therapy with azathioprine and methotrexate in the treatment of rheumatoid arthritis revisited: comment on the article by Willkens et al. [Arthritis Rheum. 1996]