Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II

Jutta Gärtner; Stephen L Hauser; Amit Bar-Or; Xavier Montalban; Jeffrey A Cohen; Anne H Cross; Kumaran Deiva; Habib Ganjgahi; Dieter A Häring; Bingbing Li; Ratnakar Pingili; Krishnan Ramanathan; Wendy Su; Roman Willi; Bernd Kieseier; Ludwig Kappos

doi:10.1177/13524585221078825

Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II

Mult Scler. 2022 Sep;28(10):1562-1575. doi: 10.1177/13524585221078825. Epub 2022 Mar 10.

Authors

Jutta Gärtner¹, Stephen L Hauser², Amit Bar-Or³, Xavier Montalban⁴, Jeffrey A Cohen⁵, Anne H Cross⁶, Kumaran Deiva⁷, Habib Ganjgahi⁸, Dieter A Häring⁹, Bingbing Li¹⁰, Ratnakar Pingili¹⁰, Krishnan Ramanathan⁹, Wendy Su¹⁰, Roman Willi⁹, Bernd Kieseier⁹, Ludwig Kappos¹¹

Affiliations

¹ Department of Paediatrics and Adolescent Medicine, Division of Paediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Göttingen, Germany.
² UCSF Weill Institute for Neurosciences, Department of Neurology, University of California - San Francisco, San Francisco, CA, USA.
³ Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁵ Department of Neurology, Mellen MS Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
⁶ Department of Neurology, Section of Neuroimmunology, Washington University School of Medicine, St Louis, MO, USA.
⁷ Department of Pediatric Neurology, University Hospitals Paris Saclay, Hôpital Bicêtre, National Reference Center for Rare Inflammatory Brain and Spinal Diseases, Le Kremlin-Bicêtre, France.
⁸ Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, UK/Statistics Department, University of Oxford, Oxford, UK.
⁹ Novartis Pharma AG, Basel, Switzerland.
¹⁰ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
¹¹ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, and Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital of Basel, University of Basel, Basel, Switzerland.

Abstract

Background: In the phase III ASCLEPIOS I and II trials, participants with relapsing multiple sclerosis receiving ofatumumab had significantly better clinical and magnetic resonance imaging (MRI) outcomes than those receiving teriflunomide.

Objectives: To assess the efficacy and safety of ofatumumab versus teriflunomide in recently diagnosed, treatment-naive (RDTN) participants from ASCLEPIOS.

Methods: Participants were randomized to receive ofatumumab (20 mg subcutaneously every 4 weeks) or teriflunomide (14 mg orally once daily) for up to 30 months. Endpoints analysed post hoc in the protocol-defined RDTN population included annualized relapse rate (ARR), confirmed disability worsening (CDW), progression independent of relapse activity (PIRA) and adverse events.

Results: Data were analysed from 615 RDTN participants (ofatumumab: n = 314; teriflunomide: n = 301). Compared with teriflunomide, ofatumumab reduced ARR by 50% (rate ratio (95% confidence interval (CI)): 0.50 (0.33, 0.74); p < 0.001), and delayed 6-month CDW by 46% (hazard ratio (HR; 95% CI): 0.54 (0.30, 0.98); p = 0.044) and 6-month PIRA by 56% (HR: 0.44 (0.20, 1.00); p = 0.049). Safety findings were manageable and consistent with those of the overall ASCLEPIOS population.

Conclusion: The favourable benefit-risk profile of ofatumumab versus teriflunomide supports its consideration as a first-line therapy in RDTN patients.ASCLEPIOS I and II are registered at ClinicalTrials.gov (NCT02792218 and NCT02792231).

Keywords: Relapsing multiple sclerosis; neurofilament light chain; no evidence of disease activity; progression independent of relapse activity; recently diagnosed; treatment-naive.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized / adverse effects
Humans
Multiple Sclerosis* / chemically induced
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / diagnosis
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Recurrence
Toluidines / adverse effects

Substances

Antibodies, Monoclonal, Humanized
Toluidines
ofatumumab

Associated data

ClinicalTrials.gov/NCT02792218
ClinicalTrials.gov/NCT02792231