title: Concomitant Methotrexate Protects Against Total Knee Arthroplasty in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors.
abstract: OBJECTIVE
  To determine the effects of concomitant methotrexate (MTX) on the incidence of total knee arthroplasty (TKA) resulting from the progression of joint destruction in patients with rheumatoid arthritis (RA) during longterm treatment with tumor necrosis factor (TNF) inhibitors.
  
  
  METHODS
  A total of 155 patients with RA (310 knee joints) received TNF inhibitors at our institute between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or swollen) knee joints in 68 patients were retrospectively studied over the course of a minimum of 5 years of followup. The median (interquartile range) followup period was 8.1 (7.0-9.3) years. All data were analyzed using the knee joint as the statistical unit of analysis. TKA during treatment with TNF inhibitors was used as the outcome variable in predictive analyses. The cumulative incidence of TKA was compared by concomitant or no MTX use (MTX±).
  
  
  RESULTS
  There were 79 subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates, the cumulative incidence of TKA for the MTX+ group was significantly lower than that for the MTX- group (24% vs 45% at 5 yrs, respectively, p = 0.035). Multivariate analysis using the Cox proportional hazards model revealed that concomitant MTX (HR 0.44, 95% CI 0.22-0.89), Larsen grade (HR 2.93, 95% CI 1.94-4.41), and older age at baseline (HR 1.04, 95% CI 1.01-1.08) were independent predictors of TKA.
  
  
  CONCLUSIONS
  Concomitant MTX reduces the incidence of TKA by 56% in patients with RA during longterm treatment with TNF inhibitors.
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine. asai@med.nagoya-u.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Nobunori
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Koji
authors.initials: K
authors.lastname: Funahashi
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Toki
authors.initials: T
authors.lastname: Takemoto
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Kenya
authors.initials: K
authors.lastname: Terabe
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Asai
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: From the Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.S. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Takahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Funahashi, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; Y. Yoshioka, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Takemoto, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; K. Terabe, MD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Asai, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; N. Ishiguro, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine; T. Kojima, MD, PhD, Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kojima
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery*; D019645:Arthroplasty, Replacement, Knee / Q000379:methods* / Q000534:rehabilitation; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011859:Radiography; D020127:Recovery of Function; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: KNEE JOINT; LONGTERM EFFECT; METHOTREXATE; RHEUMATOID ARTHRITIS; TOTAL KNEE ARTHROPLASTY; TUMOR NECROSIS FACTOR INHIBITOR