Use of Methotrexate to Induce and Maintain Remission in Crohn's Disease: A Regional Cohort Study

Abstract

Introduction/aim: There is limited data on the use of Methotrexate (MTX) for induction and maintenance of remission in children with histologically confirmed, chronic and non-remitting Crohn's Disease (CD). We therefore aimed to review our patients treated with MTX, in terms of both induction and maintenance of remission. Methods: A retrospective and prospective cohort study of patients with CD, resistant to or intolerant of Azathioprine (AZA), who were treated with MTX (16 week induction course of s/c MTX (15mg/m2) followed by the equivalent oral dose) from 1/8/97 to 31/12/05 at our regional centre. Paediatric Crohn's Disease Activity Index (PCDAI) was used as a well-validated score to objectively measure disease activity during treatment; PCDAI ≤10 indicated full remission, ≤15 indicated partial remission and a score >30 indicated severe disease. Results: 27 patients were treated with an induction course of s/c MTX; 25 (93%) patients entered remission. These 25 patients had CD diagnosed at a mean (range) age of 11.4yrs (4.0-15.6) and received MTX at a mean (range) age of 13.5yrs (9-18.0). The median PCDAI at start of treatment was 35 (IQR 22.5-40). Median time to partial/complete remission was 15 weeks (IQR 8-16), with a median duration of follow-up of 114 weeks (IQR 85-179). 8 (32%) entered clinical remission with PCDAI≤15 and maintained long-term remission (6 full remission, 2 partial remission). 17 (68%) of patients relapsed, 5 (20%) having only a single relapse and all re-entering remission (1 requiring surgery and 1 requiring a further s/c course of MTX). 12 (48%) patients had ≥2 relapses, with 7 of these patients receiving Infliximab, 1 receiving Adalimubab, 4 requiring surgery and 2 further patients undergoing assessment for surgery; 5 (20%) of these have still not entered remission. On MTX treatment, 9 (36%) had mild nausea/vomiting and 13 (52%) had raised ALT (2 subsequently undergoing liver biopsy, with treatment then continued). Summary/conclusions: MTX appears to be effective in inducing (93%) and maintaining (52% ≤ 1 relapse in median of >2 years follow-up) remission in patients who have failed to remit on AZA and also appears to be well tolerated and safe. Those who have had multiple relapses have all had complicated clinical courses and severe intractable disease. However, a stronger evidence base is needed from well- designed RCTs for both induction and maintenance of remission of CD by MTX.