Twenty-Four-Month Real-World Outcomes of Ofatumumab in Relapsing-Remitting Multiple Sclerosis: A Multicenter Retrospective Cohort Study.

Background/Objectives: Real-world evidence on ofatumumab (OFA) beyond 12 months remains limited in relapsing-remitting multiple sclerosis (RRMS). We assessed 24-month effectiveness and safety, compared treatment-naïve and previously treated patients, and explored predictors of failure to achieve No Evidence of Disease Activity-3 (NEDA-3). Methods: This multicenter retrospective cohort study included adult RRMS patients treated with OFA in routine clinical practice. Effectiveness analyses were restricted to patients with complete 24-month follow-up and full clinical and magnetic resonance imaging (MRI) assessment (complete-case analysis). Outcomes included relapses, MRI activity, Expanded Disability Status Scale (EDSS) progression, NEDA-3, and adverse events (AEs). Exploratory multivariable logistic regression was used to assess baseline predictors of NEDA-3 non-achievement. Results: Of 258 patients who initiated OFA, 148 had completed 24-month clinical and MRI follow-up and were evaluable for effectiveness. Over 24 months, 71.5% achieved NEDA-3; relapses occurred in 15.5% of patients, MRI activity in 15.5%, gadolinium-enhancing lesions (GELs) in 4.7%, and EDSS progression in 17.6%. Disease activity was minimal during months 12-24, with relapses in 2.7%, MRI activity in 2.0%, and no GELs. In unadjusted analyses, no statistically significant differences were observed between treatment-naïve and previously treated patients. Higher baseline EDSS was associated with failure to achieve NEDA-3. In the 24-month safety subgroup, AEs were recorded in 28.4% of patients; infections occurred in 26.4% of patients (all grade 1-2), and no serious adverse events were observed. Conclusions: In this multicenter real-world cohort, OFA was associated with low inflammatory disease activity over 24 months in RRMS patients with complete follow-up. These findings should be interpreted cautiously because the effectiveness analysis was restricted to a complete-case cohort and safety data were collected retrospectively.