Efficacy of parenteral methotrexate in refractory Crohn's disease

Background: Methotrexate is steroid-sparing in short-term trials for refractory Crohn's disease. This study assesses the impact of dosing and administration on the long-term utility of methotrexate in Crohn's disease. Methods: The efficacy and tolerability of methotrexate were assessed in all refractory Crohn's disease patients treated at the University of Chicago from 1 September 1989 to 6 June 1997. Results: Seventy-six patients were identified: 43% male, mean age 35 years, mean Crohn's disease duration 9.5 years. Mean methotrexate duration was 55 weeks; mean dose was 20 mg/week. Drug administration was parenteral (78%), oral (13%), or combination (8%). Improvement occurred in 63% after a mean of 9 weeks, for a mean duration of 65 weeks. Remission occurred in 37% after a mean of 22 weeks, for a mean duration of 59 weeks. Improvement and remission were highest with parenteral therapy, but dose-independent. Parenteral therapy maintained remission in 46%. Improvement (P=0.05) and remission (P=0.01) were more likely for patients under 40. Improvement rates were higher with concurrent steroids (P=0.02) or antibiotics (P=0.01). Side-effects occurred in 46%, resulting in discontinuation in 18%. Prednisone was decreased in 78%, and stopped in 40%. Conclusions: Long-term therapy with methotrexate in Crohn's disease is safe, effective, steroid-sparing, and most efficacious in younger patients and when given parenterally.