P0704 A Multicenter Study Evaluating the Persistence, Effectiveness, and Safety of Methotrexate in Patients with Inflammatory Bowel Disease: The MICI-METHO Study
Authors: Caron B , Kirchgesner J , Nachury M , Bouguen G , Uzzan M , Buisson A , Le Cosquer G , Vuitton L , Seksik P , Petit S , Wils P , Nancey S , Altwegg R , Hupe M , Fumery M , Roblin X , Laharie D , Hebuterne X , Baumann C , Vicaut E , Peyrin-Biroulet L 
Published: January 2025

Abstract

Background
Methotrexate has demonstrated efficacy in Crohn’s disease (CD) as monotherapy and is increasingly used in combination therapy. There is no consensus regarding its use in clinical practice, and it remains underused. The aims of this study were to describe the use of methotrexate in patients with inflammatory bowel disease (IBD) in France, and assess its persistence and safety.

Methods
This was an observational, retrospective, multicenter study involving adult patients with IBD treated with methotrexate in monotherapy or combination therapy between January 2015 and December 2022. All patients were followed for at least 6 months after the initiation of treatment.

Results
A total of 1115 patients were included from 15 French centers. Among them, 510 were men (45.7%). The median age at diagnosis was 24 [17.9–36.4] years, and the median age at initiation of methotrexate was 35.6 [24.8–50.3] years. The majority of patients had CD (77%), and 378 (34.5%) patients had at least one extra-intestinal manifestation (EIM). Regarding prior treatments, 45.8% of patients had been exposed to azathioprine and 78.2% to anti-TNF agents.
The median treatment duration was 12.3 [5.9–29.9] months. The primary indication for methotrexate was IBD (81.5%), followed by EIM (rheumatological (11.9%) or dermatological (3.9%)). The most frequently used induction doses were 15 mg/week (47.5%) and 25 mg/week (31%), while the most common maintenance dose was 15 mg/week (51.1%). The treatment was mainly administered by subcutaneous injection (57.8%) or orally (38%). Methotrexate was prescribed in combination therapy in 90.6% of cases.
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 sex (Hazard Ratio (HR) 1.258; 95% Confidence Interval (CI) 1.051–1.506) and the presence of EIM (HR 0.709; 95% CI 0.583–0.862). In UC, the presence of EIM (HR 0.629; 95% CI 0.420–0.944) was associated with treatment persistence.
The main reasons for discontinuation of methotrexate were inefficacy (32.5%), intolerance (29.6%), and cessation of combination therapy (20.4%). A total of 344 (31.7%) patients experienced an adverse event related to methotrexate, and 9 patients experienced a serious adverse event. After discontinuation of methotrexate, 53.8% of patients continued treatment as monotherapy, 40% required another treatment, and 6.1% underwent surgical intervention.

Conclusion
The French multicenter MICI-METHO study is the first to provide a comprehensive overview of the real-world use, effectiveness, and safety of methotrexate in patients with IBD. A better understanding of this treatment could improve its use in IBD management.