Long-term Safety of Ofatumumab in Patients With Relapsing Multiple Sclerosis
Stephen L. Hauser1, Anne H. Cross2, Kevin Winthrop3, Heinz Wiendl4, Jacqueline Nicholas5, Sven G. Meuth6, Paul S. Giacomini7, Francesco Saccà8, Ronald Zielman9, Ayan Das Gupta10, Xixi Hu11, Ratnakar Pingili11, Roseanne Sullivan11, Virginia DeLasHeras12, Wendy Su11, Ludwig Kappos13
1UCSF Weill Institute for Neurosciences, University of California, San Francisco, California, USA, 2Washington University School of Medicine, Saint Louis, Missouri, USA, 3Public Health and Preventive Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, Portland, Oregon, USA, 4University of Muenster, Muenster, Germany, 5OhioHealth Multiple Sclerosis Center, Columbus, Ohio, USA, 6Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany, 7Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, 8NSRO Department, University “Federico II” of Naples, Naples, Italy, 9Novartis Pharma B.V., Amsterdam, The Netherlands, 10Novartis Healthcare Pvt. Ltd., Hyderabad, India, 11Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA, 12Novartis Pharma AG, Basel, Switzerland, 13Research 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 the long-term safety and tolerability of ofatumumab treatment in patients with relapsing multiple sclerosis (RMS).


Ofatumumab, a fully-human anti-CD20 monoclonal antibody with a 20 mg subcutaneous monthly dosing regimen, is approved for treating RMS in adults. Previously published data demonstrated that ofatumumab treatment up to 30 months had a favorable safety profile and was generally well-tolerated. Longer-term safety of ofatumumab in RMS patients continues to be monitored.


Patients completing the core ASCLEPIOS I/II, APOLITOS and APLIOS clinical trials could enter ALITHIOS, an ongoing, open-label, umbrella extension trial. Here, we analyze the cumulative data for up to 4 years of ofatumumab treatment (data cutoff: 25-Sep-2021) in the overall (N=1969), continuous (ofatumumab in core+extension; N=1292) and newly-switched (teriflunomide core and ofatumumab extension; N=677) groups. The proportion of patients with treatment-emergent adverse events (AEs), serious AEs, serious infections including opportunistic infections, and malignancies will be assessed. Laboratory parameters including neutrophils, lymphocytes, and serum immunoglobulin (Ig) G and IgM levels will be analyzed.


In data reported from ALITHIOS with a cut-off of 29-Jan-2021, representing ofatumumab treatment for up to ~3.5 years, 83.8% of patients had ≥1 AEs (exposure-adjusted incidence rate [EAIR], 148.7) and 9.7% had ≥1 serious AEs (EAIR, 4.8) with a low incidence of serious infections (2.9%; EAIR, 1.4) and malignancies (0.6%; EAIR, 0.3). Updated safety data representing continuous ofatumumab treatment for up to 4 years will be presented, focusing on the incidence of serious infections including opportunistic infections, incidence of malignancies, and deaths. The long-term trend of IgG/IgM levels and their association with serious infections will also be investigated.


Safety findings for up to 3.5 years showed ofatumumab treatment to be well-tolerated with no new safety risks identified. This additional safety data will help confirm ofatumumab’s longer-term safety profile and provide further confidence to the MS community.