Ocrelizumab Linked to Risk For Serious Infections in Patients With MS

Patients with multiple sclerosis (MS) receiving ocrelizumab are at higher risk for serious infection compared with those treated with platform injectable therapies, according to study results presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2025, held in Barcelona, Spain from September 24 to 26, 2025.

Although ocrelizumab and other B-cell–depleting therapies are highly effective in reducing disease activity and slowing disability progression in MS, there is concern about their long-term safety, particularly with respect to infections. To further evaluate this risk, researchers conducted an observational study using retrospective data from the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research.

The researchers analyzed outcomes for 2551 patients with MS treated with ocrelizumab and compared them with a propensity-matched cohort of 1307 patients who had received platform injectable therapies. The primary endpoint was the incidence of serious infections, with secondary analyses assessing time to first serious infection, associations between hypogammaglobulinemia and infection risk, and risk differences by age group.

Patients in the ocrelizumab group experienced a significantly higher risk for serious infection compared with the comparator cohort (odds ratio [OR], 1.98; 95% CI, 1.52-2.59; P <.001). The rates of serious infection were 4.21 vs 2.64 per 100 person-years for ocrelizumab and injectable therapies, respectively. In addition, patients on ocrelizumab reached a first serious infection sooner than those on platform injectables (hazard ratio, 1.86; 95% CI, 1.45-2.39).

Reductions in immunoglobulin G (IgG) or immunoglobulin M (IgM) were not significantly associated with increased infection risk in patients treated with ocrelizumab (IgG OR, 1.36; 95% CI, 0.99-1.89; P =.07; IgM OR, 1.21; 95% CI, 0.90-1.63; P =.21). Subgroup analyses by age did not reveal meaningful differences in infection risk within the ocrelizumab cohort.

“The results provide the magnitude of this risk in comparison to platform treatment and may facilitate shared decision making between patients and providers to select disease modifying therapy,” the study authors concluded.

Disclosures: This research was supported by Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.