A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis

Aliment Pharmacol Ther. 1999 Dec;13(12):1597-604. doi: 10.1046/j.1365-2036.1999.00667.x.

Abstract

Background and aims: The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known.

Aim: To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome.

Methods: A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels.

Results: After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity.

Conclusions: For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Inflammation / drug therapy
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / blood
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Single-Blind Method
  • Time Factors
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Methotrexate