Efficacy and tolerability of methotrexate therapy for refractory Crohn's disease: a large single-centre experience

Aliment Pharmacol Ther. 2012 Jan;35(2):284-91. doi: 10.1111/j.1365-2036.2011.04925.x. Epub 2011 Nov 24.


Background: Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohn's disease (CD) as a first-line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited.

Aims: To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines.

Methods: Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow-up with maintenance therapy, were assessed via physician's global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis.

Results: Sixty-six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow-up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients.

Conclusions: These data suggest that methotrexate is effective in terms of initial response in Crohn's disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Methotrexate / adverse effects*
  • Remission Induction
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Immunosuppressive Agents
  • Methotrexate