Discontinuation of ocrelizumab in multiple sclerosis: reoccurrence of disease activity

BACKGROUND: The optimal strategy after discontinuation of B-cell depleting therapies like ocrelizumab in people with multiple sclerosis (pwMS) remains uncertain, particularly regarding delayed disease reactivation, disability progression and required treatment duration before cessation. METHODS: In this prospective two-centre observational cohort study with propensity score-matched (PSM) analysis, we evaluated recurrence of disease activity and disability worsening after ocrelizumab discontinuation. PwMS fulfilling the 2017 McDonald criteria were enrolled between January 2018 and December 2023 at two German MS centres. Participants received ocrelizumab for ≥12 months with no inflammatory activity in the preceding 12 months. Of 655 eligible patients (continuers, n=578; discontinuers, n=77), 290 were included after 4:1 PSM. The primary exposure was discontinuation, mainly due to infection concerns during COVID-19 (81%) or hypogammaglobulinaemia (16%). Main outcomes were time to combined inflammatory activity (CIA) and progression independent of relapse activity (PIRA). Receiver operating characteristic (ROC) identified optimal treatment duration. RESULTS: After median follow-up of 28.5 months, there was no significant difference in CIA risk between groups (HR: 0.91, 95% CI 0.08 to 10.79) or for PIRA (HR: 4.8, 95% CI 0.38 to 60.2). Beyond 24 months after discontinuation, disease activity remained stable, with a numerical rise that did not reach statistical significance. ROC analysis suggested no further reduction of activity beyond 29-30 months of therapy, but increasing reactivation risk after >32 months off-treatment. CONCLUSIONS: For stable pwMS, ocrelizumab discontinuation after about 30 months on-treatment appears safe short-term, though vigilant monitoring is warranted beyond 2 years off-treatment due to potential delayed reactivation.