Methotrexate in Crohn's disease: results of a randomized, double-blind, placebo-controlled trial

Hepatogastroenterology. 1999 May-Jun;46(27):1724-9.


Background/aims: Immunosuppression with methotrexate may be useful in the treatment of Crohn's disease. We tested the efficacy of methotrexate in refractory Crohn's disease in a randomized, controlled trial.

Methodology: Randomized, double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn's disease, 33% of whom had previously failed therapy with 6-mercaptopurine. Patients were given placebo or oral methotrexate 15 mg/week, or adjusted up to 22.5 mg/week, for up to 1 year or until treatment failure. Outcome was assessed by reduction in prednisone dosage, Crohn's Disease Activity Index, hospital admission, and laboratory parameters.

Results: Four patients were dropped from the study for non-compliance and one because of intercurrent illness, and 28 patients could be evaluated. Fewer methotrexate-treated patients (6/13 or 46%) had flares of Crohn's disease as compared to placebo-treated patients (12/15 or 80%), but this did not achieve statistical significance (p<0.1). There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients (3/13 or 23%) as compared to the placebo-treated patients (0/15 or 0%) (p<0.2). Laboratory indices of inflammation did not differ between the two groups.

Conclusions: The methotrexate-treated group showed a trend toward fewer Crohn's disease flares, balanced by an increased number of significant side effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Recurrence


  • Immunosuppressive Agents
  • Methotrexate