Injection-Related Reactions with Subcutaneous Administration of Ofatumumab in Relapsing Multiple Sclerosis: Data from Clinical Studies and Post Marketing Experience
John Kramer1, Ratnakar Pingili2, Ronald Zielman3, Ayan Das Gupta4, Pranava Katkuri4, Wendy Su2, Elisabeth Lucassen2, Dee Stoneman5, Olaf Hoffmann6
1St. Thomas Medical Partners, Nashville, Tennessee, USA, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States, 3Novartis Pharma B.V., Amsterdam, Netherlands, 4Novartis Healthcare Pvt. Ltd., India, 5Novartis Pharma AG, Basel, Switzerland, 6St.Josefs-Krankenhaus Potsdam

To characterize the risk of injection-related reactions (IRRs: systemic and local-site) observed in relapsing multiple sclerosis (RMS) patients treated with ofatumumab in clinical trials and post-marketing surveillance.


In the core ASCLEPIOS I/II trials, IRRs were predominantly reported with the first ofatumumab injection. Most were mild-to-moderate in severity and non-serious in nature. No life-threatening/hypersensitivity reactions leading to discontinuation were observed. Updated information on IRRs is now available from the open-label extension study ALITHIOS and post-marketing surveillance.


Data from patients treated with ofatumumab in the core ASCLEPIOS I/II trials and ALITHIOS study (overall, N=1969; patients who received continuous ofatumumab, N=1292; patients newly switched from teriflunomide to ofatumumab, N=677) and post-marketing surveillance (cut-off: 29-Jan-2021) were included in the analysis. Incidence of both systemic and local-site IRRs, their severity and seriousness were reported. The most commonly associated symptoms are summarized.


Systemic/local-site IRRs were observed in 24.6%/11.5% in overall; 25.6%/13.2% in continuous and 22.6%/8.3% in newly-switched groups. Upon first injection, incidence of systemic/local-site IRRs in overall, continuous, and newly-switched groups were 17.4%/2.9%, 17%/3.4%, and 18.2%/2.1%, respectively. Majority (99.5%) were mild-to-moderate (Grade 1/2) in severity. No life-threatening IRRs were observed during the study. In the overall population, systemic and local-site IRRs led to treatment discontinuation in 5 and 1 patient, respectively. The most common systemic IRR symptoms (≥5%) with all injections were fever, headache, chills, fatigue, and local-site IRR symptoms (≥3%) were erythema/redness and pain. From the post-marketing, 6 serious cases were assessed as potential systemic IRRs (HCP/non-HCP: 2/4): 1 patient was hospitalized with weakness. In addition, 5 patients reported serious hypersensitivity reactions (HCP/non-HCP: 1/4) including 1 anaphylaxis.


Systemic and local-site IRRs reported upon first injection with ofatumumab in the ALITHIOS trial and post-marketing surveillance were mostly mild-to-moderate in severity. These results are consistent with the Phase 3 ASCLEPIOS I/II trials.