Rituximab use in multiple sclerosis patients was linked to a higher risk of inflammatory bowel disease (IBD) in a Swedish population-based cohort, researchers reported.
Higher IBD Risk Observed
The crude incidence rate of IBD reached 110 per 100,000 person-years among rituximab users, compared with 13 per 100,000 for other disease-modifying therapies and 41 per 100,000 in the general population. The difference was driven primarily by the rituximab group.
After adjusting for age, sex and MS characteristics, the hazard ratio for comparator therapies versus rituximab was 0.10 (95% CI 0.04-0.22), indicating a markedly lower risk with the alternatives. The analysis therefore suggested that the relative increase was substantial, even though the absolute numbers remained modest.
Even so, the cumulative incidence of IBD remained under 2% at ten years for the rituximab cohort, showing that absolute risk stays low despite the relative increase.
Study Details and Findings
Anti-CD20 drugs are among the most effective agents for reducing acute inflammatory activity in MS. Although rituximab never received formal approval for the disease, it has become Sweden’s most frequently prescribed off-label MS therapy. The investigators noted that its widespread use made the safety signal particularly important for clinicians.
Recent safety alerts have highlighted possible IBD associations with rituximab, ocrelizumab and ofatumumab; the ocrelizumab label already carries a warning for immune-mediated colitis. Safety discussions around anti-CD20 agents have traditionally focused on severe infections and diminished vaccine responses, prompting the team to examine gastrointestinal outcomes specifically.
The Swedish MS Register supplied the data set, and it identified 9,251 patients who initiated rituximab or a comparator drug, natalizumab, dimethyl fumarate or fingolimod, between 2011 and 2023. Each case was matched to population controls, allowing a direct comparison of event rates across groups.
Therapy episodes totaled 13,748: 6,481 for rituximab, 2,976 for natalizumab, 2,767 for dimethyl fumarate and 1,524 for fingolimod, plus 61,065 matched general-population episodes.
During the observation period, 164 IBD events were recorded: 40 among rituximab users, 4 with comparator drugs, and 120 in the population sample. Crohn’s disease accounted for 62% of rituximab-related cases versus 29% in the broader cohort, indicating a skew toward that subtype in the exposed group.
In a fully adjusted model, the number needed to harm at five years was 131 (95% CI 93-228) for rituximab compared with other DMTs.
The outcome definition was based on ICD codes for Crohn’s disease, ulcerative colitis or indeterminate colitis recorded on separate dates. Although colonoscopy data were unavailable, stricter ICD-based criteria yielded consistent risk estimates, supporting the reliability of the findings.