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Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent-onset rheumatoid arthritis treated according to the Disease Activity Score
  1. Sjoerd M. van der Kooij (smvanderkooij{at}lumc.nl)
  1. Leiden University Medical Center, Netherlands
    1. Jeska K. De Vries-Bouwstra (jkdevriesbouwstra{at}lumc.nl)
    1. VU Medical Center, Netherlands
      1. Yvonne P.M. Goekoop-Ruiterman (y.p.m.goekoop{at}lumc.nl)
      1. Leiden University Medical Center, Netherlands
        1. Derkjen van Zeben (j.vanzeben{at}sfg.nl)
        1. Sint Franciscus Hospital, Netherlands
          1. Pit J.S.M. Kerstens (p.kerstens{at}janvanbreemen.nl)
          1. Jan van Breemen Institute, Netherlands
            1. Andreas H. Gerards (agerards{at}ssvz.nl)
            1. Vlietland Hospital, Netherlands
              1. Johannes H.L.M. van Groenendael (whisperwoods{at}cs.com)
              1. Franciscus Hospital, Netherlands
                1. Johanna M.W. Hazes (j.hazes{at}erasmusmc.nl)
                1. Erasmus Medical Center, Netherlands
                  1. Ferdinand C. Breedveld (f.c.breedveld{at}lumc.nl)
                  1. Leiden University Medical Center, Netherlands
                    1. Cornelia F. Allaart (c.f.allaart{at}lumc.nl)
                    1. Leiden University Medical Center, Netherlands
                      1. Ben A.C. Dijkmans (bac.dijkmans{at}vumc.nl)
                      1. VU Medical Center, Netherlands

                        Abstract

                        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
                        • methotrexate
                        • recent-onset RA

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