ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Safety and Efficacy of B cell Therapy in Older People with Mul:ple Sclerosis
Provisionally accepted
Turlough Montague*
Yuuki KangKaren ThomasNicole Burke SimpsonCelia MillerSophie Chatterton
Ariadna Fontes VillalbaJohn Parratt- Royal North Shore Hospital, St Leonards, Australia
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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, 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 to younger cohorts, though immunoglobulin decline and discontinuation due to adverse effects highlight the need for monitoring.
Keywords: Anti-CD20 monoclonal antibodies, disease modifying therapies, Immunosenecence, multiple sclerois, Ocrelizumab, Ofatumumab, old age., PIRA
Received: 05 Sep 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Montague, Kang, Thomas, Burke Simpson, Miller, Chatterton, Fontes Villalba and Parratt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Turlough Montague
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