Risk of Inflammatory Bowel Disease After Anti-CD20 Treatment in Multiple Sclerosis.

IMPORTANCE

Anti-CD20 biologics are widely used as disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), but recent reports have raised concerns about an increased risk of inflammatory bowel disease (IBD) during treatment. This study aimed to assess treatment-associated IBD risk in individuals with RRMS.

OBJECTIVE

To compare the risk of new-onset IBD across different therapies for RRMS and relative to the general population.

DESIGN, SETTING, AND

PARTICIPANTS

This was a population-based cohort study conducted in Sweden. Through the Swedish MS register, initiations of rituximab, natalizumab, dimethyl fumarate, and fingolimod were identified between January 1, 2011, and December 31, 2023, in individuals with RRMS aged 18 to 55 years with at least 10 years of lookback time (5 years for dispensed drugs) and no evidence of previous IBD. These initiations were matched with general population comparator episodes selected from the Swedish population.

EXPOSURES: Rituximab, comparator DMTs (natalizumab, dimethyl fumarate, fingolimod), or general population comparator.

MAIN OUTCOMES AND MEASURES: New-onset IBD, defined as 2 or more records on separate dates with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes K50 (Crohn disease), K51 (ulcerative colitis), and/or K52.3 (indeterminate colitis).

RESULTS

Among the 13 748 therapy episodes (6481 rituximab, 2976 natalizumab, 2767 dimethyl fumarate, 1524 fingolimod) in 9251 individuals (range in mean ages of the exposure groups, 35-38 years) and 61 065 matched general population episodes, 164 IBD events occurred during follow-up (40 with rituximab, 4 with comparator DMTs, and 120 in the general population). The crude incidence rate of IBD was 110 (95% CI, 76-147) per 100 000 person-years for rituximab, 13 (95% CI, 3-30) for the comparator DMTs, and 41 (95% CI, 34-48) for the general population. After adjustment for demographics and MS characteristics, the hazard ratio for the comparator DMTs vs rituximab was 0.10 (95% CI, 0.04-0.22). In the rituximab group, 62% of IBD events were classified as Crohn disease compared with 29% in the general population. The number needed to harm for rituximab vs the comparator DMTs was 131 (95% CI, 93-228) at 5 years, after full adjustment.

CONCLUSIONS AND RELEVANCE: Results of this cohort study show that rituximab was associated with an increased risk of IBD compared with other modern MS therapies, after adjustment for differences in characteristics at therapy start. Clinicians and individuals with MS should consider IBD risk in treatment decisions and remain vigilant for gastrointestinal symptoms during anti-CD20 therapy.