Introduction The case for methotrexate (MTX) therapy has been comprehensively compiled in Crohn’s disease, with trials showing its efficacy in both induction and maintenance of remission. By contrast, the evidence remains patchy for ulcerative colitis (UC). BSG guidelines recommend its trial as a second-line agent in those patients intolerant of, or resistant to, azathioprine (AZA) or mercaptopurine (MP). Previous studies show conflicting results for MTX in UC; with response rates between 22–33%, with a high rate of colectomy, 44%, in one of the studies. We aimed to review the clinical effectiveness of MTX in our cohort of UC patients who had previously tried, or failed, with thiopurine therapy.
Methods A retrospective analysis of patients taking MTX for UC was carried out. Subjects were identified from our inflammatory bowel disease database. All patients had trialled thiopurine therapy prior to MTX. Their outcomes on these treatments, including reasons for discontinuation, were recorded. It is current policy within our department to start with oral MTX (plus folate supplementation), initially 15 mg once weekly, increasing to 20mg or 25mg as necessary. Clinical response at 12 weeks and 12 months was used to assess efficacy of MTX treatment. The primary endpoint was steroid-free remission.
Results A total of 21 UC patients (male = 62%) were identified. Median age was 61 years (range 21–82). Disease pattern was extensive (43%), left-sided (19%), and recto-sigmoid (38%). Reasons for AZA/MP discontinuation were intolerance to therapy (38%), and failure of therapy (62%) despite dose optimisation.
Steroid-free remission was achieved in 11 patients (52%), and this appears sustained at 12 months follow-up. A further 4 patients (19%) report improved symptoms with MTX, but remain dependent on low-dose steroids (although it is noted that 1 of these patients has co-existent rheumatoid arthritis which may explain this). MTX was discontinued in 4 patients (19%) because of a lack of clinical response (n = 1), side-effects (n = 2) or planned pregnancy (n = 1). Side-effects reported with MTX were liver toxicity and skin rashes. A final 2 patients (10%) have shown promising results with MTX but are not yet eligible for 12-month follow-up. Of the 21 patients included, 20 remain on oral therapy, and one has switched to parenteral MTX. Of note, none of the MTX patients have progressed to colectomy, in contrast to previous studies.
Conclusion Our study has shown good efficacy with MTX, with approximately half of UC patients achieving steroid-free clinical remission at 12 months. In contrast to previous studies, our experience suggests it is a useful treatment option in patients previously failing or intolerant of optimised thiopurine therapy.
Disclosure of Interest None Declared.