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

Background and aims: The optimum initial dose of methotrexate for steroid-r equiring inflammatory bowel disease is not known. Aim: To compare directly the efficacy and toxicity of methotrexate 15 and 2 5 mg/week, and to explore the value of methotrexate blood levels as predict ors of outcome. Methods: A 16-week randomized single-blind comparison of subcutaneous metho trexate 15 or 25 mg/week was performed in 32 patients with steroid-requirin g Crohn's disease or ulcerative colitis. Patients who did not respond to me thotrexate 15 mg/week were further studied for an additional 16 weeks on me thotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate level s. 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 pa tients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity w as not different between the treatment groups. Methotrexate blood levels di d not predict efficacy or toxicity. Conclusions: For induction of remission in steroid-requiring inflammatory b owel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/we ek are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.