Ofatumumab Reduces Clinical and Radiological Activity in People with Recently Diagnosed Treatment-naive Relapsing Multiple Sclerosis Irrespective of Baseline Serum Neurofilament Light Chain Levels
Gabriel Pardo1, Ludwig Kappos2, Anne Cross3, Jens Kuhle4, Xavier Montalban5, Natalia Khachanova6, Alit Bhatt7, Rebecca Piccolo8, Jing Xi9, Ibolya Boer10, Douglas Arnold11, Enrique Alvarez12, Tjalf Ziemssen13
1Oklahoma Medical Research Foundation, 2RC2NB, University Hospital Basel, 3Washington University School of Medicine, 4Neurologic Clinic and Policlinic and MS Center, 5Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia, 6Russian National Research Medical University N.I. Pirgov, 7Novartis Healthcare Pvt. Ltd, 8Novartis Pharmaceuticals Corporation, 9Novartis, 10Novartis Pharma AG, 11Montreal Neurological Institute, McGill Univ, 12University of Colorado, 13University Clinic Dresden
Objective:
To compare the efficacy of ofatumumab versus teriflunomide in reducing relapses and new/enlarging T2 (neT2) lesions in recently diagnosed (within 3 years) treatment-naive (RDTN) people with relapsing multiple sclerosis (pwRMS) based on their baseline serum neurofilament light chain (sNfL) levels.
Background:
Data from the Phase 3 ASCLEPIOS I/II trials (ofatumumab versus teriflunomide in pwRMS) demonstrated that baseline sNfL levels were prognostic for on-study lesion formation in the overall population, including a subgroup of RDTN participants.
Design/Methods:
A baseline sNfL cut-off was predefined by the median sNfL value for the overall population across the ASCLEPIOS I/II trials; RDTN participants were stratified into high (≥median [9.3 pg/mL]) and low (<9.3 pg/mL) sNfL categories. Adjusted annualized relapse rates (ARR) and annualized neT2 lesion rates were assessed with ofatumumab versus teriflunomide in each sNfL category over the study duration (up to 30 months). The effect of treatment on the proportion of participants achieving no evidence of disease activity (NEDA-3) at Month 12 and 24 was also compared within each sNfL category.
Results:
Across 576 RDTN participants with baseline sNfL available, annualized relapse rates were reduced by 63.4% (p=0.002) and 37.2% (p=0.119) in the high and low sNfL categories, respectively, with ofatumumab versus teriflunomide. Ofatumumab reduced the annualized rate of neT2 lesions by 85.5% and 85.8% versus teriflunomide for high and low sNfL categories, respectively (both p<0.001). A higher proportion of participants achieved NEDA-3 status with ofatumumab versus teriflunomide treatment, regardless of baseline sNfL levels (p<0.001 in both sNfL groups at all timepoints).
Conclusions:
Ofatumumab was consistently associated with reductions in clinical and radiological activity versus teriflunomide in RDTN participants regardless of their baseline sNfL levels. The results support the benefit of using high-efficacy therapies, such as ofatumumab, at an early stage in the MS disease course irrespective of sNfL levels.