Risk of infection in ocrelizumab-treated adults with multiple sclerosis aged 55 years and older: a retrospective cohort study

Summary: Background: Pivotal trials for ocrelizumab in multiple sclerosis (MS) excluded adults >55 years old. This study aimed to compare rates of infection and infection-related hospitalization between ocrelizumab-treated and unexposed older adults with MS. Methods: A retrospective cohort study was performed, analyzing the electronic medical records, June 2017–January 2026, at the Massachusetts General Hospital, comparing 800 older adults with MS who received at least 600 mg of ocrelizumab IV to 800 older adults who never received B-cell depleting therapies. Infection and related hospitalization rates were modeled using inverse probability of treatment weighting and negative binomial regression with person-time offsets. Findings: Among 1600 adults (n = 1111, 69.4% female; n = 1496, 93.5% White; median ages 64 (range 55–88) for ocrelizumab and 67 years (range 55–98) for unexposed), median follow-up was 3.5 vs. 8.2 years. There were 429 infection-related hospitalizations (164 ocrelizumab, 265 unexposed), 10 infection-associated deaths (2 ocrelizumab, 8 unexposed), and 4538 infections (1597 ocrelizumab, 2941 unexposed). After adjustment, ocrelizumab was associated with a higher infection-associated hospitalization rate (IRR 1.67; 95% CI 1.15–2.43; p = 0.008) and infections (IRR 1.42; 95% CI 1.20–1.68; p < 0.001). Higher disability and comorbidity independently increased the risk of both outcomes. Female sex was associated with a higher infection risk (IRR 1.36, 95% CI 1.12–1.64, p = 0.002), driven mostly by urinary tract infections, which accounted for 91.46% of the observed sex difference. Interpretation: In adults aged ≥55 years with MS, ocrelizumab was associated with higher rates of infection-related hospitalization and infections. Findings support individualized risk-benefit discussion, especially regarding UTIs in older patients of female sex, dedicated UTI monitoring and prevention protocols for older ocrelizumab-treated patients, and inclusion of this age group in future clinical trials. Funding: Investigator-initiated grant from Genentech .