Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. A randomized, double-blind study.

OBJECTIVE

To compare the effects of azathioprine and methotrexate on progression of radiologic damage in patients with rheumatoid arthritis.

DESIGN

Double-blind, randomized 48-week trial.

PATIENTS

Sixty-four patients with active rheumatoid arthritis who either have not responded to or who have reacted with side effects to at least parenteral gold and D-penicillamine.

INTERVENTIONS

Either azathioprine, 100 mg daily, or methotrexate, 7.5 mg weekly, was administered orally. Depending on the clinical effect after 8 weeks, the dosage was increased to either azathioprine, 150 mg, or methotrexate, 15 mg. The dosages for nonsteroidal anti-inflammatory drugs and prednisone were held stable.

MEASUREMENTS

Clinical and laboratory assessments were done by the same physician every 4 weeks for the first 24 weeks and every 8 weeks thereafter. Radiographs of hands, wrists, and feet obtained at baseline and after 24 and 48 weeks were scored by one rheumatologist blinded to medication and clinical findings.

MAIN RESULTS

Initial radiologic scores were comparable in both groups and correlated with disease duration (r = 0.38). An intention-to-treat analysis after 24 and 48 weeks showed significantly fewer new erosions in the methotrexate group compared with the azathioprine group (difference, 2.0 [95% CI, 0.2 to 3.9] and 3.5 [CI, 1.3 to 5.8], respectively). The change in total joint score was also significantly less pronounced in the methotrexate group compared with the azathioprine group after 24 weeks (difference, 2.8 [CI, 0.2 to 5.2]) and after 48 weeks (difference, 3.9 [CI, 0.3 to 7.4]). Radiologic stabilization after 48 weeks was present in 10% of the azathioprine group compared with 29% of the methotrexate group.

CONCLUSIONS

Patients with rheumatoid arthritis treated with low-dose methotrexate showed significantly less radiologic progression than patients treated with azathioprine. This result suggests that methotrexate therapy is clinically superior in these patients.