title: Addition of another disease-modifying anti-rheumatic drug to methotrexate reduces the flare rate within 2 years after infliximab discontinuation in patients with rheumatoid arthritis: an open, randomized, controlled trial.
abstract: OBJECTIVE
  We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARDs) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare.
  
  
  METHODS
  RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with C-reactive protein) scores < 2.6 for ≥ 6 months with IFX were randomized either to receive addition of bucillamine (BUC) to MTX (BUC + MTX group; n = 24) or not (MTX group; n = 31) upon discontinuing IFX. The primary endpoint was the flare rate within 2 years of IFX discontinuation.
  
  
  RESULTS
  Six patients discontinuing MTX during the study were excluded from analyses. Seventeen patients (63.0%) experienced flares in the MTX group, which was significantly reduced in the BUC + MTX group (31.8%; p = 0.045). Further, the flare rates differed significantly between remission and non-remission by a Boolean definition upon IFX discontinuation in the MTX group (40.0% vs. 91.7%, respectively; p = 0.014), but they were comparable in the BUC + MTX group. BUC treatment was interrupted in seven patients due to rash, proteinuria and incompliance.
  
  
  CONCLUSIONS
  DMARDs combination therapy may be a better treatment strategy than MTX monotherapy for maintaining RA control after successful discontinuation of biological agents.
authors.affiliation: Department of Rheumatology/Clinical Immunology, Saitama Medical Center, Saitama Medical University , Kawagoe, Saitama , Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kurasawa
authors.forename: Hayato
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Amano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Hideto
authors.initials: H
authors.lastname: Kameda
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D003545:Cysteine; C026535:bucillamine; D008727:Methotrexate
keywords: Biological agents; Bucillamine; DMARD combination; Flare; Remission