Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease

Gastroenterology. 2014 Mar;146(3):681-688.e1. doi: 10.1053/j.gastro.2013.11.024. Epub 2013 Nov 21.


Background & aims: 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. number, NCT00132899.

Keywords: COMMIT; IBD; Inflammatory Bowel Disease; Randomized Controlled Trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • C-Reactive Protein / metabolism
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infliximab
  • Kaplan-Meier Estimate
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prednisone / therapeutic use
  • Treatment Outcome


  • Antibodies, Monoclonal
  • C-Reactive Protein
  • Infliximab
  • Prednisone
  • Methotrexate

Associated data