Effect of Longer-term Ofatumumab Treatment on Disability Progression and Brain Volume Change
Jeffrey Cohen1, Stephen Hauser2, Ronald Zielman3, Ayan Das Gupta4, Amin Azmon5, Jing Xi6, Gina Mavrikis Cox7, Derrick Robertson8, Heinz Wiendl9, Ludwig Kappos10
1Department of Neurology, Mellen MS Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA, 2UCSF Weill Institute for Neurosciences, Department of Neurology, University of California - San Francisco, San Francisco, CA, USA, 3Novartis Pharma B.V., Amsterdam, The Netherlands, 4Novartis Healthcare Pvt. Ltd., Hyderabad, India, 5Novartis Pharma A.G., Basel, Switzerland, 6China Novartis Institutes for BioMedical Research Co., Ltd, Shanghai, China, 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 8Multiple Sclerosis Division, Department of Neurology, University of South Florida, Tampa, FL, USA, 9University of Muenster, Muenster, Germany, 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, Basel, Switzerland

To assess confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), relapse-associated worsening (RAW), and brain volume change (BVC) in relapsing multiple sclerosis patients receiving ofatumumab for up to 5 years.


In the ASCLEPIOS I/II core studies, ofatumumab (3-/6-month[m] CDW: 10.90%/8.15%) delayed disability accrual compared with teriflunomide (3/6mCDW: 14.98%/11.95%). PIRA was the main contributor to overall 3m/6mCDW.


Results are presented for up to 4 years (ASCLEPIOS + ALITHIOS open-label extension) in patients on continuous ofatumumab and those switched from teriflunomide in the extension; 4- and 5-year data to be presented at congress. 6mCDW, PIRA (CDW events without confirmed relapses prior to CDW), RAW (event onset <90 days from a relapse), and BVC (percent brain volume change[PBVC] and annualized rates of change in brain volume[ABVC]) were assessed (full analysis set).


Of 1882 patients randomized in ASCLEPIOS I/II (ofatumumab/teriflunomide:946/936), 1367 entered ALITHIOS (continuous/switch:690/677). Most patients were free from 3m/6mCDW events during the studies (ofatumumab: 85.0%; teriflunomide: 80.7%). Up to 4 years (cut off: 25-Sep-2021), 119/946 (12.6%) and 148/936 (15.8%) patients had 6mCDW in the continuous and switch groups, respectively. In the continuous group, the 6mPIRA Kaplan-Meier cumulative event rate[KM-CER] remained low (11.0%) and 6mPIRA accounted for the majority of patients, i.e., 86/119 (72.3%; core:65.9%; extension:92.9%) whereas 6mRAW (KM-CER: 3.5%) accounted for only 30/119 (25.2%) patients (core:30.8%; extension:7.1%). Up to 4 years, overall mean PBVC remained low, –1.42% and –1.62% for the continuous and switch groups, respectively (at week 240). ABVC for continuous ofatumumab remained low in the core (–0.34%/year) and extension (–0.28%/year). In the switch group, ABVC was –0.42%/year(core) and –0.29%/year(extension).


With longer-term ofatumumab treatment, disability progression was predominantly PIRA, the annual rate of BVC remained low, and low rates of CDW/PIRA indicated that most patients remained free from disease progression. Outcomes favored early, compared with later, initiation with ofatumumab.