IgE-mediated allergic reactions to ocrelizumab in multiple sclerosis: A retrospective cohort study

Background: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, is widely used in multiple sclerosis (MS). Infusion-related reactions (IRRs) are common, while IgE-mediated allergic reactions are rare and poorly characterized. Objectives: To evaluate the incidence and risk factors of IgE-mediated allergic reactions to ocrelizumab in MS patients. Methods: We retrospectively analyzed MS patients treated with ocrelizumab (2018-2024) at a single center. Severe IRRs (grade ≥3) underwent allergologic assessment, including skin prick tests (SPT) and intradermal tests (IDT). Predictors of IgE-mediated reactions were explored. Results: Among 387 patients, 94 (24.3%) developed IRRs; 19 (4.9%) were grade 3. Six cases (1.6%) were classified as IgE-mediated based on positive IDT and clinical presentation; all had negative SPTs. A history of allergic disease was more frequent among IgE-positive patients (66.7% vs. 26.5%, p=0.028). Allergy history (OR 11.5, p=0.009) and fewer ocrelizumab infusions (OR 0.60, p=0.047) were independent risk factors. Switching to ofatumumab was well tolerated in five out of six. Conclusions: IgE-mediated allergic reactions to ocrelizumab are uncommon but important to recognize. IDT with immediate reading is useful for diagnosis. A history of allergy may help identify high-risk patients. Ofatumumab is a safe alternative in confirmed cases.