Ofatumumab for multiple sclerosis with disability accumulation

Background: The ASCLEPIOS/APLIOS/APOLITOS/ALITHIOS trials highlighted the benefits of ofatumumab in reducing relapse rates and disability progression in multiple sclerosis (MS). However, its effects on patients with severe disability status remains uncertain. This study aimed to clarify the outcomes of ofatumumab in MS patients with high Expanded Disability Status Scale (EDSS) scores and prolonged disease durations. Methods: This is a retrospective cohort study of MS patients treated with ofatumumab at an MS center in Japan. At 12 months of treatment, patients with MS starting ofatumumab were classified into the treatment-responsive or treatment-resistant groups based on ofatumumab continuity, incidence of relapses with EDSS worsening, progression independent of relapse activity (PIRA). We used logistic regression analysis to identify factors associated with ofatumumab response. Results: Seventy patients were included in the analysis; 39 (56 %) patients were relapsing-remitting (RR), and 31 (44 %) patients were secondary progressive (SP) MS. Mean age at ofatumumab initiation, age at onset, and disease duration were 48.0, 33.9, and 14.1 years, respectively. The median EDSS was 4.5 (3.0-6.5); 38(56 %) patients were classified as resistant. The resistant rates by disease type were 33 % (13/39) and 81 % (26/31) for RR and SP MS, respectively. On multivariate analysis, EDSS and No evidence of disease activity (NEDA) 3 were independent factors for ofatumumab responsiveness (OR, 1.74, 0.04; 95 % CI, 1.17-2.73, 0.00-0.47; p = 0.01, 0.04). Conclusion: Ofatumumab may yield more favorable effects when initiated in patients with MS with lower EDSS scores.