Safety and efficacy of B-cell therapy in older people with multiple sclerosis

Background: The MS population is aging, with nearly one-third now over 55 years. This group is underrepresented in trials and less often prescribed high-efficacy therapy (HET). Although phase III studies of ocrelizumab and ofatumumab confirmed efficacy in younger patients, the risk-benefit profile in older people with MS (opwMS) is less established given reduced relapse activity and higher risks of infection and malignancy. Methods: We retrospectively reviewed opwMS (≥ 55 years) treated with ocrelizumab or ofatumumab at a tertiary centre, evaluating clinical outcomes, MRI activity, and adverse events. Results: Among 140 patients (67% (94) female, mean age 63), median disease duration was 16 years and B-cell therapy duration 44 months; 91% (127) had prior DMT exposure. During treatment, 77.9% (109) achieved NEDA-3, EDSS remained stable (3.38 to 3.44, p=0.67), and PIRA was reduced by 15%. Adverse events occurred in 50.7% (71%), leading to discontinuation in 10.7% (15). Immunoglobulin levels fell significantly (IgM, IgA, and IgG). In 47 patients ≥ 65 years, adverse event rates were similar, 69.6% (33) achieved NEDA-3, but EDSS increased (p=0.034). Conclusion: Over 44 months, B-cell therapy in opwMS (mean age 63) showed safety and efficacy comparable with younger cohorts, although immunoglobulin decline and discontinuation due to adverse effects highlight the need for monitoring.