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

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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.