Efficacy of Early Ofatumumab vs Late Switch From Teriflunomide: Subgroup Analysis of the ALITHIOS Open-label Extension Study by Previous Disease-Modifying Therapy Exposure and Age
Heinz Wiendl1, Jeffrey Cohen2, Ralf Gold3, Jerome De Seze4, Derrick Robertson5, Sibyl Wray6, Francesco Sacca7, Ronald Zielman8, Amin Azmon9, Miriam King9, Simone Fantaccini9, Ludwig Kappos10
1University of Muenster, 2Department of Neurology, Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, 3Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, 4University Hospital of Strasbourg, 5Multiple Sclerosis Division, Department of Neurology, University of South Florida, 6Hope Neurology MS Center, 7Department (NSRO), University “Federico II” of Naples, 8Novartis Pharma B.V., 9Novartis Pharma AG, 10Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel
Objective:
To compare clinical and MRI outcomes in patients with relapsing multiple sclerosis initiating ofatumumab (OMB) in the phase 3 ASCLEPIOS I/II study (core) vs switching from teriflunomide (TER) to OMB in ALITHIOS (open-label extension), according to age and number of previous disease-modifying therapies (DMTs).
Background:
In ASCLEPIOS I/II (NCT02792218/NCT02792231), OMB (fully human anti-CD20 monoclonal antibody) reduced annualized relapse rate (ARR), MRI lesion activity, and delayed disability worsening vs TER. Patients entering ALITHIOS (NCT03650114) continued OMB or switched from TER to OMB.
Design/Methods:
Cumulative clinical and MRI outcomes (ARR, time to 3- or 6-month confirmed disability worsening [3/6mCDW], number of gadolinium-enhancing [Gd+] T1 lesions, annualized T2 lesion rate) were analyzed in patients who received and continued OMB (OMB-OMB) and patients who switched from TER to OMB (TER-OMB) according to number of previous DMTs (0, 1, 2, >2, any) and age (≤40y, >40y).
Results:
946/936 received OMB/TER in the core and 690/677 continued/switched to OMB in the open-label extension. ARR was significantly reduced by 68.3-76.6% in the TER-OMB group and reduced by 39.9-65.1% in the OMB-OMB group in the open-label extension. Lowest mean ARR was achieved in the OMB-OMB group for patients with ≤1 previous DMT (0.046-0.049). Switching to or continuing OMB was associated with a reduced risk of 3/6mCDW, with the greatest benefit observed in OMB-OMB patients with ≤1 DMT or age ≤40y. Near complete suppression of T1 Gd+ activity was observed in the TER-OMB group (90.00-100% across all subgroups) and sustained in the OMB-OMB group. New/enlarging T2 lesions showed a similar, though delayed, suppression in the TER-OMB group. Incidence of adverse events was consistent with ASCLEPIOS I/II.
Conclusions:
Switching from TER to OMB reduced clinical and MRI disease activity across all previous DMT and age subgroups, particularly for younger patients and those treated with ≤1 DMT, highlighting the importance of earlier treatment initiation.