Methotrexate for inflammatory bowel disease: the MICI-METHO multicenter retrospective cohort study

Methotrexate has demonstrated efficacy in Crohn's disease (CD) as monotherapy and is increasingly used in combination therapy. We investigated for the first time the use of methotrexate in a very large cohort of patients with inflammatory bowel disease (IBD) in a real-world setting.

This was an observational, retrospective, multicenter study including consecutive adult IBD patients treated with methotrexate in monotherapy or combination therapy between January 2015 and December 2022 in 15 French centers.

Among the 1115 patients included, 77% had CD and 34.5% had at least one extra-intestinal manifestation (EIM). Regarding prior treatments, 44.0% of patients had been exposed to azathioprine and 75.1% to anti-tumor necrosis factor agents. The primary indication for methotrexate was IBD (81.5%), followed by EIM (rheumatological [11.9%] or dermatological [3.9%]). Methotrexate was prescribed in combination therapy in 90.6% of cases. The most frequent induction and maintenance dose was 15 mg/week (47.5% and 51.1% respectively). The persistence rate of methotrexate was 27.7 months in CD and 22.4 months in ulcerative colitis (UC). For CD, factors associated with persistence were female gender (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.05-1.51) and the presence of EIM (HR 0.71; 95% CI 0.58-0.86), and for UC, the presence of EIM (HR 0.63; 95% CI 0.42-0.94). Among the 344 (31.7%) patients who experienced an adverse event related to methotrexate, nine experienced a serious adverse event.

The French multicenter MICI-METHO study is the first to provide a comprehensive overview of the real-world use, persistence, and safety of methotrexate in patients with IBD.