• Yi Chao Foong, Daniel Merlo, Melissa Gresle, Katherine Buzzard, Michael Zhong, Wei Zhen Yeh, Vilija Jokubaitis, Mastura Monif, Olga Skibina, Serkan Ozakbas, Francesco Patti, Pierre Grammond, Maria Pia Amato, Tomas Kalincik, Dana Horakova, Eva Kubala Havrdova, Bianca Weinstock-Guttman, Jeanette Lechner Scott, Cavit Boz, Maria Jose Sa, Helmut Butzkueven, Anneke van der Walt, Chao Zhu, and MSBASE study group.
• Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
• J. Neurol. Neurosurg. Psychiatr. 2024 Mar 7.

BackgroundOngoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60.MethodsUsing data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI).ResultsA total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years.ConclusionIn older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

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