Abstract
Background: Ocrelizumab, a monoclonal antibody targeting CD20+ B cells, is a high-efficacy treatment for relapse onset MS. The specific patient subgroups that benefit most from ocrelizumab remain uncertain.
Objective: Compare the effectiveness of ocrelizumab with fingolimod, natalizumab and alemtuzumab in clinically relevant scenarios.
Methods: Patients with relapse-onset MS treated with ocrelizumab, fingolimod, natalizumab or alemtuzumab for ⩾6 months were identified from MSBase, OFSEP and Danish MS registries. Pairwise comparisons were conducted in the overall cohort and 14 predefined subgroups by sex, disease activity, MS duration, EDSS, prior therapy and treatment cessation reason. Outcomes (relapses, progression independent of relapse activity [PIRA], relapse associated worsening [RAW], and disability improvement) were compared in pairwise-censored weighted groups.
Results: Fingolimod, natalizumab, and alemtuzumab had higher relapse rates (all p<0.001) and relapse risks (HRs: 2.26, 1.35, 1.48) versus ocrelizumab. Fingolimod and natalizumab had higher risk of RAW (HR 1.62; 1.77). Disability improvement was lower with fingolimod. Ocrelizumab superiority persisted across subgroups, particularly patients not treatment naïve, recently active, or who stopped prior therapy for inefficacy. There was no evidence for a difference in PIRA or disability improvement compared to natalizumab/alemtuzumab.
Conclusion: Ocrelizumab treatment provides superior control of relapses (±RAW), especially in patients with on-treatment disease activity. RAW is rare on high-efficacy therapy. Treatment of PIRA remains an unmet need.