Efficacy and tolerability of methotrexate therapy for refractory Crohn's disease: a large single-centre experience

Background Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohns disease (CD) as a first-line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited. Aims To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines. Methods Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow-up with maintenance therapy, were assessed via physicians global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis. Results Sixty-six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow-up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients. Conclusions These data suggest that methotrexate is effective in terms of initial response in Crohns disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.