TOPLINE

Among adults aged 55 years or older with multiple sclerosis (MS), those exposed to ocrelizumab, an antibody therapy for individuals with MS, had higher rates of infection-related hospitalization and infection overall than those who were never exposed to any B-cell-depleting therapy, with urinary tract infections (UTIs) emerging as the leading type of infection observed.

METHODOLOGY

• Researchers conducted a retrospective cohort study using electronic medical records from Massachusetts General Hospital to examine the safety profile of ocrelizumab among individuals with MS.
• They included 1600 participants with MS aged 55 years or older: 800 who received ≥ 600 mg of intravenous ocrelizumab (median age, 64 years; ocrelizumab group) and 800 who never received B-cell-depleting therapies (median age, 67 years; unexposed group). 
• The primary outcome was the infection-related hospitalization rate, and the secondary outcome was the reported infection rate. The median follow-up duration was 3.5 years in the ocrelizumab group vs 8.2 years in the unexposed group.
• Researchers used inverse probability of treatment weighting and negative binomial regression to adjust for confounders.

TAKEAWAY

• Overall, 429 hospitalizations linked to infection (164 in the ocrelizumab group and 265 in the unexposed group), 10 deaths attributed to infection (two in the ocrelizumab group and eight in the unexposed group), and 4538 individual infection events (1597 in the ocrelizumab group and 2941 in the unexposed group) were recorded in the cohort.
• After adjusting for baseline differences, exposure to ocrelizumab was associated with higher rates of infection-related hospitalization (incidence rate ratio [IRR], 1.67; P = .008) and overall infection (IRR, 1.42; P ≤ .001) than no exposure to B-cell-depleting therapies.
• Women in the cohort showed a 36% higher rate of infection than men in the cohort (IRR, 1.36; P = .002), and further analysis attributed 91.46% of this disparity specifically to UTIs.
• A higher comorbidity burden and a higher baseline Expanded Disability Status Scale score each independently predicted a greater risk for both hospitalization (IRR, 1.34 and 1.56, respectively) and infection (IRR, 1.21 and 1.16, respectively; all P < .001).
• In a model restricted to UTIs alone, ocrelizumab exposure (IRR, 1.94; P < .001) and female sex (IRR, 1.97; P = .001) were each independently associated with a higher risk for UTIs.

IN PRACTICE

"Our 1:1 allocated study of 1600 older adults with MS, each diagnosed, evaluated, and characterized by a neurologist since the introduction of ocrelizumab onto the U.S. market, allows longer-term follow-up of ocrelizumab treated people with MS, including the risks of infections, hospitalization-associated infections, and deaths," the study authors wrote.

SOURCE

The study was led by Seungwon Lee, Northwestern University in Chicago. It was published online on September 24, 2026, in The Lancet Regional Health - Americas.

LIMITATIONS

The retrospective design, inconsistent follow-up, and possible immortal time bias may have skewed risk estimates, an issue compounded by substantial missing baseline disability data. The study findings stemmed from one academic with predominantly White population, which limited generalizability.

DISCLOSURES

This study was funded by an investigator-initiated grant from Genentech. One author reported receiving funding from Amgen, Genentech, Novartis, and TG Therapeutics and consulting fees from Alexion, Amgen, Genentech/Roche, and Novartis. The other authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.