Background: In patients with early rheumatoid arthritis, initial combination therapies provide earlier clinical improvement and less progression of joint damage after 1 year compared with initial monotherapies (as demonstrated in the BeSt study).
Objective: To evaluate whether the initial clinical and radiographic efficacy of combination therapies could be maintained during the second year of follow-up in patients with early rheumatoid arthritis.
Design: Randomized, controlled clinical trial with blinded assessors.
Setting: 18 peripheral and 2 university medical centers in the Netherlands.
Patients: 508 patients with early active rheumatoid arthritis.
Intervention: Sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Trimonthly treatment adjustments were made to achieve low disease activity.
Measurements: Primary end points were functional ability (Health Assessment Questionnaire) and Sharp-van der Heijde score for radiographic joint damage.
Results: Groups 3 and 4 had more rapid clinical improvement during the first year; all groups improved further to a mean functional ability score of 0.6 (overall, P = 0.257) and 42% were in remission (overall, P = 0.690) during the second year. Progression of joint damage remained better suppressed in groups 3 and 4 (median scores of 2.0, 2.0, 1.0, and 1.0 in groups 1, 2, 3, and 4, respectively [P = 0.004]). After 2 years, 33%, 31%, 36%, and 53% of patients in groups 1 through 4, respectively, were receiving single-drug therapy for initial treatment. There were no significant differences in toxicity.
Limitations: Patients and physicians were aware of the allocated group, and the assessors were blinded.
Conclusions: Currently available antirheumatic drugs can be highly effective in patients with early rheumatoid arthritis in a setting of tight disease control. Initial combination therapies seem to provide earlier clinical improvement and less progression of joint damage, but all treatment strategies eventually showed similar clinical improvements. In addition, combination therapy can be withdrawn successfully and less treatment adjustments are needed than with initial monotherapies.