Ocrelizumab Discontinuation vs. Continuation After Safety Events: Comparative Insights from MSBase

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Introduction: Ocrelizumab (OCR), a CD20+ B-cell depleting monoclonal antibody, is a highly effective therapy for Multiple Sclerosis (MS). However, safety concerns may lead to treatment discontinuation, raising questions about the clinical consequences of such decisions.

This propensity score-matched study utilized data from the MSBase registry to compare outcomes between patients discontinuing OCR due to safety concerns ("Switchers") and those continuing treatment ("Continuers"). Matching was performed using inverse probability of treatment weighting (IPTW) to balance treatment duration and baseline characteristics. Primary outcomes included annualized relapse rate (ARR), time to first relapse, 24-48 weeks confirmed disability worsening (CDW), and progression independent of relapse activity (PIRA).

From an initial cohort of 310 Switchers and 1,315 Continuers, 66 patients who experienced at least one safety event and switched from OCR were matched with 66 Continuers. PS-IPTW analyses revealed higher ARR in Switchers (0.08, 95% CI: 0.05-0.14) versus Continuers (0.038, 95% CI: 0.02-0.07; p=0.040). Time to first relapse showed no significant difference (HR=2.23, 95% CI: 0.68-7.28; p=0.183). Trends toward increased CDW24 weeks risk (PS-IPTW HR=2.11, 95% CI: 0.93-4.75; p=0.073), while no significant difference was found at 48 weeks (HR=1.81, 95% CI: 0.83-3.30; p=0.201). PIRA risk showed a trend toward an increase in Switchers (HR=2.45, 95% CI: 0.95-6.29; p=0.063).

In this propensity-score-matched analysis, OCR discontinuation due to safety concerns was associated with increased relapse activity and trends toward greater disability progression. These findings highlight the importance of maintaining therapeutic intensity and systematic monitoring during treatment transitions to mitigate safety risks Conclusion: Further research is needed to develop strategies for effectively managing adverse events to optimize patient outcomes.