Five-Year Safety and Efficacy Outcomes with Ofatumumab in Patients with Relapsing Multiple Sclerosis
Stephen L. Hauser, Jeffrey A. Cohen, de Sèze, Sven G. Meuth, Paul S. Giacomini, Jin Nakahara, Celia Oreja‐Guevara, Derrick Robertson, Sibyl Wray, Alit Bhatt, Xixi Hu, Jing Xi, Rebecca Piccolo, Valentine Jehl, Roseanne Sullivan, Ibolya Boer, Heinz Wiendl, Ludwig Kappos
Abstract
INTRODUCTION: Ofatumumab demonstrated superior efficacy and similar safety versus teriflunomide in ASCLEPIOS I/II in people with relapsing multiple sclerosis; no new safety concerns and sustained efficacy were observed up to 4 years in the open-label extension study ALITHIOS. Here, we further characterise the safety and efficacy of ofatumumab up to 5 years by discussing infection outcomes in the COVID-19 era and providing a comprehensive overview of participant disability outcomes. METHODS: Safety (N = 1969; participants who received ≥ 1 dose of ofatumumab in ASCLEPIOS I/II, APLIOS, APOLITOS, or ALITHIOS) and efficacy sets (N = 1882; participants randomised to ofatumumab [OMB-OMB] or teriflunomide [TER-OMB] in ASCLEPIOS I/II, regardless of whether they entered ALITHIOS) were analysed. Data cutoff: 25 September 2022. RESULTS: The exposure-adjusted incidence rates (per 100 patient-years) of adverse events (AEs, 124.65), serious AEs (4.68), serious infections (1.63), and malignancies (0.32) remained consistent with previous findings up to 5 years of follow-up, with no new safety signals identified. With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse rates (ARR) remained low, and magnetic resonance imaging (MRI) activity was almost completely suppressed with OMB-OMB through years 1-5; after switching from teriflunomide (years 2-3), pronounced reductions in ARR/MRI activity were observed with low rates sustained through years 3-5. During year 5, 9 of 10 participants in both groups were free of disease activity (NEDA-3). CONCLUSION: Ofatumumab has a favourable benefit-risk profile that is sustained up to 5 years. TRIAL REGISTRATION: ALITHIOS (NCT03650114): https://clinicaltrials.gov/ct2/show/NCT03650114.