TOPLINE

A new real-world cohort study of more than 1100 patients with inflammatory bowel disease (IBD) provided important evidence on methotrexate use outside clinical trials, showing that it was prescribed predominantly as combination therapy with biologics and had a median treatment duration of approximately 1 year. Although adverse events were reported by a notable proportion of patients, serious toxicity was uncommon.

METHODOLOGY

• Methotrexate is an established but underused immunosuppressant in IBD, used mainly in Crohn’s disease and sometimes with anti-TNF therapy to reduce immunogenicity, while its benefit in ulcerative colitis remains unproven.
• Researchers conducted a retrospective, multicenter observational study across 15 French centers by including 1115 adult patients with IBD (859 with Crohn’s disease and 256 with ulcerative colitis) who were started on methotrexate between January 2015 and December 2022.
• Participants had a median age of 35.6 years at methotrexate initiation; 77.0% had Crohn’s disease, 75.1% had previously received anti-TNF biologics, and 34.5% had at least one extraintestinal manifestation. A minimum follow-up of 6 months was required after the initiation of methotrexate.
• The analysis not only assessed prescribing practices, treatment persistence, effectiveness using the Harvey-Bradshaw Index for Crohn’s disease and the partial Mayo score for ulcerative colitis, and safety outcomes but also identified factors associated with methotrexate persistence.

TAKEAWAY

• Methotrexate was mainly used as an adjunct to biologic therapy rather than as monotherapy, with combination therapy used in 90.6% of cases; 15 mg/wk was the most common overall induction and maintenance dose, and subcutaneous administration was more frequent than oral administration (57.8% vs 38.0%).
• The median treatment duration was 12.3 months; for Crohn’s disease, female sex (hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and the presence of extraintestinal manifestations (HR, 0.71; 95% CI, 0.58-0.86) were associated with methotrexate persistence, while for ulcerative colitis, only the presence of extraintestinal manifestations (HR, 0.63; 95% CI, 0.42-0.94) showed association with persistence.
• When methotrexate was discontinued, the most common reasons were inefficacy (32.5%), intolerance or side effects (29.6%), and stopping combination therapy (20.4%).
• Among 344 patients (31.7%) who experienced adverse events, the most commonly reported were gastrointestinal (13.1%), liver toxicity (6.3%), and skin disorders (3.2%), with nine patients (0.8%) developing serious adverse events.

IN PRACTICE

“This study has described for the first time the use of methotrexate in a large cohort of patients with IBD, its persistence, real-world use, and tolerability and identified factors associated with treatment persistence,” the authors of the study wrote.

“Methotrexate is less commonly used than thiopurines in combination with biologics. Most robust data on combination therapy are derived from thiopurines (eg, SONIC trial), while evidence for methotrexate remains limited to few randomized studies such as COMMIT, underscoring the relevance of real-life data to complement existing literature,” they added.

SOURCE

The study was led by Bénédicte Caron, Department of Gastroenterology, Nancy University Hospital, and INSERM, University of Lorraine, Nancy, France. It was published online in the Journal of Crohn’s and Colitis.

LIMITATIONS

The study had several limitations, including its retrospective nature and potential recall bias. Effectiveness could only be assessed descriptively rather than with a more robust comparative analysis. The cohort reflected real-world clinical practice where methotrexate is less commonly used than thiopurines in combination with biologics.

DISCLOSURES

The study received no external funding. Multiple authors reported having consulting, counseling, lecture, or speaking engagements or receiving personal fees, research grants, travel or transport support, or board memberships from pharmaceutical companies. Some also reported participating in educational activities or being part of advisory boards.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.