2023 American Academy of Neurology Abstract Website

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

Objective:

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.

Background:

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.

Design/Methods:

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).

Results:

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).

Conclusions:

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.