title: Effects of Concomitant Methotrexate on Large Joint Replacement in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors: A Multicenter Retrospective Cohort Study in Japan.
abstract: OBJECTIVE
  To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors.
  
  
  METHODS
  A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias.
  
  
  RESULTS
  Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6-8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20-0.65). Additionally, propensity score-matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032).
  
  
  CONCLUSIONS
  Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oguchi
authors.affiliation: Nagoya Medical Center, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Toyohashi Municipal Hospital, Toyohashi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Tokyo Shinjuku Medical Center, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yabe
authors.affiliation: Toyota Kosei Hospital, Toyota, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kanayama
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobunori
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Funahashi
authors.affiliation: Ichinomiya Municipal Hospital, Ichinomiya, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hanabayashi
authors.affiliation: Toyohashi Municipal Hospital, Toyohashi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirabara
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toki
authors.initials: T
authors.lastname: Takemoto
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Terabe
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Asai
authors.affiliation: Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D019643:Arthroplasty, Replacement / Q000379:methods / Q000706:statistics & numerical data*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan; D007595:Joint Prosthesis; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D008727:Methotrexate