title: Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease.
abstract: OBJECTIVE
  Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone.
  
  
  METHODS
  In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50.
  
  
  RESULTS
  Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated.
  
  
  CONCLUSIONS
  The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment with prednisone. ClincialTrials.gov number, NCT00132899.
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: brian.feagan@robartsinc.com.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: John W D
authors.initials: JW
authors.lastname: McDonald
authors.affiliation: Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Enns
authors.affiliation: Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.affiliation: Department of Medicine, Western University, London, Ontario, Canada; London Health Sciences Centre, South Street Hospital, London, Ontario, Canada.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Ponich
authors.affiliation: Hôtel-Dieu de Lévis, Lévis, Quebec, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Bourdages
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Macintosh
authors.affiliation: Centre Hospitalier Universitaire de Québec-Pavillon St. François d'Assise, Quebec City, Quebec, Canada.
authors.forename: Chrystian
authors.initials: C
authors.lastname: Dallaire
authors.affiliation: Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Cohen
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
authors.affiliation: Hôpital St. Sacrement, Quebec City, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Paré
authors.affiliation: McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.affiliation: Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saibil
authors.affiliation: The Liver and Intestinal Research Centre, Vancouver, British Columbia, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Anderson
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Donner
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Wong
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Zou
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Vandervoort
authors.affiliation: Robarts Clinical Trials, Western University, London, Ontario, Canada.
authors.forename: Marybeth
authors.initials: M
authors.lastname: Hopkins
authors.affiliation: Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Greenberg
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D000069285:Infliximab; D011241:Prednisone; D008727:Methotrexate
keywords: COMMIT; IBD; Inflammatory Bowel Disease; Randomized Controlled Trial