title: A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis.
abstract: OBJECTIVE
  A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT).
  
  
  METHODS
  In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks.
  
  
  RESULTS
  The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI.
  
  
  CONCLUSIONS
  The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
authors.affiliation: Saitama Medical Center and the Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Abe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Kondo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nagaya
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007596:Joints / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010147:Pain Measurement; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D000069285:Infliximab; D008727:Methotrexate