Radiological and clinical results of longterm treatment of rheumatoid arthritis with methotrexate and azathioprine

Objective. To study whether the reported superior effect of methotrexate (MTX) compared to azathioprine (AZA) in retarding radiologic progression after one year in rheumatoid arthritis was sustained at 2 and 4 years. Methods. All 64 patients enrolled in the original randomized double blind study were invited for an open extension of followup to 4 years including 4-monthly clinical and laboratory assessments and radiographs of hands, wrists, and feet at 2 and 4 years. Results. After 4 years, 18 patients (58%) from the MTX group and 7 patients (21%) from the AZA group continued the initial study drug. During followup more patients (n = 21) switched from AZA to MTX than vice verse (n = 5), In an intention-to-treat analysis improvement of clinical and laboratory variables at 4 years was more pronounced in the MTX group. Mean radiologic scores increased in both treatment groups during followup, According to an intention-to-treat analysis increase in erosion score at one and 2 years in the MTX group was significantly lower than in the AZA group. after one year MTX group 1.8 versus AZA group 5.3 (p = 0.002); after 2 years MTX 3.5 versus AZA 6.5 (p = 0.05). After 3 years there was a trend toward less progression in the MTX group: MTX 6.8 versus AZA 10.8 (p = 0.09), For the total score, progression in the MTX group was less after one and 2 years. After 4 years marked radiologic progression was observed more often in the AZA group. Conclusion, Drug continuation after 4 years of followup was better for MTX than for AZA. in an intention-to-treat analysis the beneficial effect of MTX on radiologic progression compared with AZA was sustained after 2 years of followup. Thereafter differences between treatment groups leveled off, probably mainly due to the greater number of switches from AZA to MTX than vice versa.