Objectives: To determine the efficacy of subsequent DMARD therapies after initial methotrexate (MTX) failure in patients with recent-onset rheumatoid arthritis (RA), treated according to the DAS for 2 years.
Methods: In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15-25 mg/week. Patients who discontinued methotrexate because of insufficient clinical response (DAS >2.4) or toxicity were classified as ″MTX failures″. In group 1, these patients switched to sulfasalazine (SSA), next leflunomide, and finally to MTX+infliximab (IFX). In group 2, ″MTX failures″ added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX+IFX. ″MTX successes& [Prime] were patients who achieved a DAS ≤2.4 after 2 years while still on methotrexate monotherapy. Total Sharp/van der Heijde Score (TSS) progression from 0-2 years was assessed in ″MTX failures″ versus ″MTX successes″.
Results: After 2 years, 162/244 patients (66%) had discontinued methotrexate because of insufficient response or toxicity. Of these, 78% also failed on sulfasalazine (adding or switching), 87% subsequently failed on leflunomide (in group 1), and 64% on MTX+SSA+HCQ (in group 2). Thirty-four of 48 patients (71%) in groups 1 and 2 were successfully treated with MTX+IFX. After 2 years, regardless of the ″ success″ on subsequent DMARDs, ″MTX failures″ had a median TSS progression of 3 units (mean 9) versus 1 unit (mean 3) in ″MTX successes″ (p=0.007).
Conclusion: After failure on initial methotrexate, treatment with subsequent conventional DMARDs is unlikely to result in a DAS ≤2.4 and allows progression of joint damage.
- conventional DMARD therapy
- joint damage progression
- recent-onset RA