Treatment of recent-onset rheumatoid arthritis: lessons from the BeSt study

Abstract

Objective: To determine the efficacy, toxicity, utilities, and costs of 4 treatment strategies for patients with recent-onset rheumatoid arthritis (RA).

Methods: 508 patients with recent-onset active RA [mean Disease Activity Score (DAS) 4.4, mean Health Assessment Questionnaire score 1.4] were randomized into 4 strategy groups: (1) sequential monotherapy; (2) step-up to combination therapy [both starting with methotrexate (MTX)]; (3) initial combination therapy with MTX, sulfasalazine, and prednisone; (4) initial combination therapy with MTX and infliximab. Treatment adjustments were based on 3-monthly calculations of the DAS (target DAS ? 2.4), by research nurses who were blinded to the strategy group. They also collected data on treatment toxicity, functional ability, costs, and utilities. Yearly anonymized radiographs of hands and feet were scored in random order by 2 independent physicians, using the Sharp/van der Heijde score.

Results: Functional ability improved significantly earlier in Groups 3 and 4 than in Groups 1 and 2, but was comparable among the groups at the end of the first year of treatment. Radiographic joint damage progression was significantly lower in Groups 3 and 4 than in Groups 1 and 2, but low in all groups compared to other RA populations, probably due to DAS-driven treatment adjustments in all groups. More patients in Groups 3 and 4 than in Groups 1 and 2 achieved clinical remission (DAS 1.6), and patients who achieved early continued remission in Groups 3 and 4 had significantly less joint damage progression than those who achieved the same in Groups 1 and 2. More patients could taper and stop all antirheumatic drugs and still retained remission in Group 4 (17% at t = 3 years) than in the other groups (10%, 5%, 9%, respectively). Toxicity was comparable between groups. Quality of life measures were significantly higher in Group 4 than in the other groups, but costs of treatment were also the highest in Group 4. Depending on the method used, higher productivity in Group 4 compensated for the higher medical costs.

Conclusion: In patients with recent-onset RA, initial combination therapy including prednisone or infliximab results in earlier clinical improvement and less joint damage progression than initial monotherapy. Initial treatment with infliximab resulted in the highest quality of life, highest productivity, and highest medical costs. DAS-driven treatment adjustments were effective to suppress disease activity and damage progression in all groups.