Comparative effectiveness of ocrelizumab in subgroups of patients with multiple sclerosis: a multi-registry...

Ocrelizumab, a monoclonal antibody targeting CD20+ B cells, is a high-efficacy therapy for multiple sclerosis (MS).

Patients with relapse-onset MS treated with ocrelizumab, fingolimod, natalizumab or alemtuzumab for ≥6 months were identified from three registries: MSBase, OFSEP and Danish MS Registry. Pairwise comparisons were performed in the overall cohort and 14 predefined clinicodemographic subgroups based on sex, disease activity, MS duration, Expanded Disability Status Scale, prior therapy and reason for prior treatment cessation. Relapses, progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) were compared in pairwise-censored groups.

Fingolimod was associated with a higher annualised relapse rate (ARR) (0.14 vs 0.06, p<0.001), relapse risk (HR 2.26, 95% CI 1.98 to 2.58), RAW (1.62, 1.08 to 2.43) and lower risk of disability improvement (0.78, 0.63 to 0.96) than ocrelizumab. Superiority of ocrelizumab over fingolimod on relapses was maintained in all subgroups. Natalizumab was associated with marginally higher ARR (0.10 vs 0.07, p<0.001), relapse risk (1.35, 1.16 to 1.57) and RAW (1.77, 1.07 to 2.94) than ocrelizumab. Alemtuzumab was associated with higher ARR (0.18 vs 0.12, p<0.001) and relapse risk (1.48, 1.25 to 1.76) than ocrelizumab, but there was no evidence for a difference in risk of RAW. There was no evidence for a difference on PIRA in any comparisons. Ocrelizumab was superior to natalizumab and alemtuzumab on relapses in patients who were not treatment-naïve, experienced disease activity on the prior therapy or stopped prior therapy due to lack of efficacy.

Ocrelizumab provides superior control of relapses and RAW, especially among patients with prior on-treatment disease activity. Treatment of PIRA remains an unmet need.