Inflammatory Bowel Disease Risk After Anti-CD20 Treatment in MS

RESEARCHERS have found that anti-CD20 treatment in multiple sclerosis (MS) has been associated with a higher risk of inflammatory bowel disease (IBD) than other modern disease-modifying therapy (DMT) options, according to a new Swedish population-based cohort study.

Anti-CD20 Treatment in MS

Anti-CD20 biologics have become widely used as DMT for relapsing-remitting MS, but recent reports have raised concerns about IBD during treatment. The risk of new-onset inflammatory bowel disease with anti-CD20 treatment in MS had not previously been assessed at population level.

Swedish Register Cohort Design

Initiations of rituximab, natalizumab, dimethyl fumarate, and fingolimod between January 2011 and December 2023 were identified in individuals with relapsing-remitting MS aged 18–55 years and no previous IBD, then matched with general population comparator episodes.

Overall, 13,748 therapy episodes (6,481 rituximab, 2,976 natalizumab, 2,767 dimethyl fumarate, and 1,524 fingolimod) in 9,251 individuals and 61,065 general population episodes were analysed. The primary outcome was new-onset IBD, defined as two or more records on separate dates for Crohn disease, ulcerative colitis or indeterminate colitis.

Inflammatory Bowel Disease Incidence Rates

During follow-up, 164 IBD events occurred (40 with rituximab, four with comparator DMTs and 120 in the general population). The crude incidence rate per 100,000 person-years was 110 (95% confidence interval [CI]: 76–147) for rituximab, 13 (95% CI: 3–30) for comparator DMTs and 41 (95% CI: 34–48) for the general population.

After adjustment, the hazard ratio for comparator DMTs versus rituximab was 0.10 (95% CI: 0.04–0.22). The number needed to harm for rituximab versus comparator DMTs was 131 (95% CI: 93–228) at 5 years.

Crohn disease accounted for 62% of IBD events with rituximab versus 29% in the general population, and 30% of those with IBD on rituximab discontinued treatment just before or within 2 years of diagnosis.

Implications for Treatment

These findings have indicated that rituximab is associated with an increased risk of IBD compared with other modern MS therapies. Clinicians and individuals with MS should consider inflammatory bowel disease risk in anti-CD20 treatment decisions and remain vigilant for gastrointestinal symptoms, although the observational design means causality cannot be inferred.

Reference

Kallin S et al. Risk of inflammatory bowel disease after anti-CD20 treatment in multiple sclerosis. JAMA Neurol. 2026;DOI:10.1001/jamaneurol.2026.3439.