A new retrospective study published in the Journal of Crohn's and Colitis offers the most comprehensive real-world look yet at methotrexate use in inflammatory bowel disease (IBD). Researchers analyzed data from 1,115 adult IBD patients across 15 French centers treated between 2015 and 2022 — the vast majority of whom had Crohn's disease.

The findings confirm that methotrexate is rarely used alone: 90.6% of patients received it as combination therapy alongside a biologic. The most common dose was 15 mg/week, typically given subcutaneously, and the median treatment duration was just over a year. Discontinuation was most often driven by inefficacy (32.5%), side effects (29.6%), or stopping combination therapy (20.4%).

Key Takeaways:

• Extraintestinal manifestations were linked to better treatment persistence in both Crohn's disease and ulcerative colitis
• Female sex was associated with lower persistence in Crohn's disease patients
• Serious adverse events were rare, occurring in only 0.8% of patients
• Most common side effects were GI-related (13.1%), liver toxicity (6.3%), and skin disorders (3.2%)

Why it matters: Methotrexate remains underused compared to thiopurines in IBD, and robust clinical trial data is limited. This large real-world dataset helps fill that gap, giving clinicians clearer guidance on dosing, persistence, and safety in everyday practice.