Ocrelizumab Carries a Higher Infection Burden in Older Adults With MS
Among adults aged 55 years and older living with multiple sclerosis, ocrelizumab was associated with more infections and more infection-related hospitalizations than no exposure to B-cell depleting therapy. The signal matters because the pivotal trials that established the drug’s role in MS largely left this age group out, even though older patients make up a growing share of clinical practice and often bring a heavier burden of disability, frailty, and comorbidity to treatment decisions.
The cohort study drew from electronic medical records at Massachusetts General Hospital between June 2017 and January 2026 and included 1,600 adults: 800 treated with at least 600 mg of intravenous ocrelizumab and 800 who had never received B-cell depleting therapies. Median age was 64 years in the ocrelizumab group and 67 years in the unexposed group. Women made up 69.4% of the cohort, and 93.5% of participants were White.
The follow-up window was longer in the unexposed group, with a median of 8.2 years versus 3.5 years among those receiving ocrelizumab, a difference that reflects the complexity of retrospective care and long-term observation rather than a simple head-to-head trial structure. Even with weighting and regression methods designed to reduce baseline imbalance, the clinical picture remained consistent: older adults on ocrelizumab experienced more infectious complications.
Infection-Related Hospitalization Rose Alongside Overall Infections
Across the full cohort, there were 4,538 infections and 429 infection-related hospitalizations. Of those events, 1,597 infections and 164 hospitalizations occurred in the ocrelizumab group, compared with 2,941 infections and 265 hospitalizations in the unexposed group. Infection-associated deaths were uncommon, with 10 total deaths recorded: 2 among ocrelizumab-treated patients and 8 among unexposed patients.
After adjustment using inverse probability of treatment weighting and negative binomial regression with person-time offsets, ocrelizumab was associated with a higher rate of infection-related hospitalization (IRR 1.67; 95% CI 1.15-2.43; p = 0.008) and a higher rate of infections overall (IRR 1.42; 95% CI 1.20-1.68; p < 0.001). Those estimates point in the same direction: in an older MS population, B-cell depletion tracked with more clinically meaningful infectious harm, not just more minor outpatient events.
The biological logic is straightforward. Ocrelizumab depletes CD20-positive B cells, a mechanism that can blunt humoral immune responses and reduce the ability to generate or sustain protective antibody responses against common pathogens. In older adults, immune senescence, cumulative disability, bladder dysfunction, and repeated healthcare exposure can stack on top of that mechanism, creating an environment where infection risk becomes harder to contain.
Disability, Comorbidity, and Urinary Tract Infections Shaped the Risk Profile
Higher disability and higher comorbidity each independently increased the risk of both infection outcomes. In routine neurology practice, that is the population in which infection risk often becomes the main reason to reconsider continued immunotherapy. Limited mobility, catheter use, impaired bladder emptying, aspiration risk, and slower recovery from common bacterial infections can turn otherwise manageable infections into hospitalizations.
Female sex was also associated with a higher infection risk overall (IRR 1.36; 95% CI 1.12-1.64; p = 0.002). The difference was driven mostly by urinary tract infections, which accounted for 91.46% of the observed sex difference. In practical terms, urinary infections were not a marginal finding buried in the data; they were the dominant explanation for why women in this cohort experienced more infections.
That pattern fits everyday MS care. Older women with neurologic disability often face a convergence of urinary retention, incontinence, recurrent bacteriuria, and interrupted symptom reporting, all of which can let a lower-tract infection progress before it is recognized. In a patient receiving B-cell depletion, a UTI may be more than a nuisance infection—it may be the event that triggers emergency evaluation, antibiotic exposure, delirium, or admission.
The investigators’ conclusion aligns with that bedside reality. The findings support a more individualized risk-benefit discussion for older adults, especially those with female sex and recurrent urinary infections, before and during ocrelizumab therapy. A blanket approach to treatment is difficult to justify when age, disability, and comorbidity materially change the infection profile.
What Neurology Practice Needs to Account for Now
This cohort does not overturn ocrelizumab’s role in MS, but it does narrow the context in which the drug should be used in older patients. The safety question in a 30-year-old with active inflammatory disease is not the same as the safety question in a 72-year-old with progressive disability and recurrent UTIs. Older adults have less physiologic reserve, more competing causes of infection, and more to lose from hospitalization.
The most actionable implication is not simply to count infections after the fact. It is to anticipate them. Older ocrelizumab-treated patients likely warrant dedicated UTI surveillance, bladder-focused prevention strategies, and deliberate reassessment of whether ongoing B-cell depletion is still delivering enough benefit to justify the infectious burden. In patients with repeated urinary infections or escalating disability, the threshold for modifying therapy will often need to be lower than it would be in younger adults.
The study also exposes a larger gap in MS evidence generation. Adults older than 55 years remain underrepresented in pivotal immunotherapy trials, even though they are increasingly common in clinical practice. Without their inclusion, safety estimates are forced to come from retrospective data such as this one, where treatment selection and follow-up duration can never be perfectly equalized. Future trials that enroll older adults with MS will be needed to clarify whether infection risk changes by disability level, comorbidity burden, or repeated exposure over time.
For now, the data offer a direct warning: in older adults with MS, ocrelizumab was linked to more infections, more infection-related hospitalizations, and a urinary tract infection burden that fell disproportionately on women. The study was investigator initiated with funding from Genentech, but the clinical question it raises is larger than any single sponsor or center—how to preserve disease control in an aging MS population without pushing infection risk beyond what patients can safely absorb.