title: Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score.
abstract: OBJECTIVE
  To determine the efficacy of subsequent disease modifying antirheumatic drug (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 MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as "MTX failures." In group 1, these patients switched to sulfasalazine (SSA), then 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" were patients who achieved a DAS </=2.4 after 2 years while still on MTX 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 MTX because of insufficient response or toxicity. Of these, 78% also failed on SSA (adding or switching), 87% subsequently failed on leflunomide (in group 1), and 64% on MTX + SSA + HCQ (in group 2). 34 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).
  
  
  CONCLUSIONS
  After failure on initial MTX, treatment with subsequent conventional DMARDs is unlikely to result in a DAS </=2.4 and allows progression of joint damage.
authors.affiliation: Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands. smvanderkooij@lumc.nl
authors.forename: Sjoerd M
authors.initials: SM
authors.lastname: van der Kooij
authors.forename: Jeska K
authors.initials: JK
authors.lastname: de Vries-Bouwstra
authors.forename: Yvonne P M
authors.initials: YP
authors.lastname: Goekoop-Ruiterman
authors.forename: Derkjen
authors.initials: D
authors.lastname: van Zeben
authors.forename: Pit J S M
authors.initials: PJ
authors.lastname: Kerstens
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Gerards
authors.forename: Johannes H L M
authors.initials: JH
authors.lastname: van Groenendael
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.forename: Ferdinand C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: Cornelia F
authors.initials: CF
authors.lastname: Allaart
authors.forename: Ben A C
authors.initials: BA
authors.lastname: Dijkmans
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001175:Arthrography; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D000069285:Infliximab; D007555:Isoxazoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012460:Sulfasalazine / Q000008:administration & dosage; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007555:Isoxazoles; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D000069285:Infliximab; D000077339:Leflunomide; D011241:Prednisone; D008727:Methotrexate