A nationwide Swedish cohort study led by Karolinska Institutet researchers and published in JAMA Neurology reveals that multiple sclerosis patients treated with rituximab face a tenfold higher risk of developing inflammatory bowel disease compared to alternative treatments. Although the relative risk is significantly elevated, researchers note that the absolute risk remains low, with less than 2% of patients affected over 10 years. Clinicians are advised to balance these risks against relapse-prevention benefits.
Increased IBD risk with rituximab
- ▪In a study published in JAMA Neurology, the crude incidence rate of inflammatory bowel disease was 110 per 100,000 person-years for rituximab, compared with 13 for comparator disease-modifying treatments and 41 for the general population.
- ▪A total of 164 inflammatory bowel disease events occurred during follow-up in the Swedish cohort study, comprising 40 events with rituximab, four with comparator treatments, and 120 in the general population group.
- ▪After adjusting for demographics and multiple sclerosis characteristics, researchers found that the risk of inflammatory bowel disease was approximately 10 times higher with rituximab than with comparator disease-modifying treatments.
Breakdown and absolute risk of IBD cases
- ▪Among inflammatory bowel disease events recorded in the rituximab group during the Swedish cohort study, 62% were classified as Crohn's disease, compared with 29% in the general population comparator group.
- ▪In a fully adjusted model from the Swedish cohort study, treating 131 patients with rituximab for five years instead of comparator disease-modifying treatments resulted in approximately one additional case of inflammatory bowel disease.
- ▪Fewer than 2% of patients in any treatment group in the Swedish cohort study developed inflammatory bowel disease within 10 years of starting treatment.
Swedish study cohort and design
- ▪Karolinska Institutet researchers analyzed data from Swedish registers covering 9,251 multiple sclerosis patients aged 18 to 55 who initiated treatment with rituximab or comparator disease-modifying treatments between 2011 and 2023.
- ▪The Swedish cohort study evaluated 13,748 therapy episodes, consisting of 6,481 for rituximab, 2,976 for natalizumab, 2,767 for dimethyl fumarate, and 1,524 for fingolimod, matched against 61,065 general population episodes.
- ▪Researchers defined new-onset inflammatory bowel disease in the Swedish cohort study as two or more medical records on separate dates with ICD codes for Crohn's disease, ulcerative colitis, or indeterminate colitis.
Evidence for an anti-CD20 class effect
- ▪The prescribed prescribing label for the anti-CD20 drug ocrelizumab includes an official warning for immune-mediated colitis.
- ▪Karolinska Institutet researcher Peter Alping stated that the observed association between rituximab and inflammatory bowel disease is likely a class effect across anti-CD20 therapies based on drug biology.
- ▪Reports in the FDA Adverse Event Reporting System have raised safety concerns regarding inflammatory bowel disease risk following treatment with anti-CD20 drugs including rituximab, ocrelizumab, and ofatumumab.
Clinical recommendations for anti-CD20 use
- ▪Karolinska Institutet researcher Peter Alping advised caution when considering initiating anti-CD20 therapy in multiple sclerosis patients who have a pre-existing history of inflammatory bowel disease.
- ▪Karolinska Institutet researcher Peter Alping recommended that clinicians and multiple sclerosis patients remain vigilant for gastrointestinal symptoms during treatment with anti-CD20 therapies.
- ▪Karolinska Institutet researcher Peter Alping emphasized that the increased risk of inflammatory bowel disease must be weighed against the significant benefits of anti-CD20 drugs in preventing multiple sclerosis relapses.
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