Up to 8 Years of Ofatumumab Treatment Demonstrates Stable Long-term Safety Profile in Relapsing Multiple Sclerosis

Long-term safety data for ofatumumab (Kesimpta; Novartis), a fully human antiCD20 monoclonal antibody approved for relapsing multiple sclerosis (RMS), continue to demonstrate a consistent safety profile across up to 8 years of treatment, according to an updated analysis of data from ASCLEPIOS I/II, APOLITOS, APLIOS, ARTIOS, and the umbrella extension study ALITHIOS.¹ The data were presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18 to 22 in Chicago, Illinois.

According to the AAN abstract, exposure-adjusted incidence rates (EAIRs, per 100 patient-years) of 112.95 and 124.96 for any adverse event (AE) were observed in the overall and recently diagnosed, treatment-naive (RDTN) populations, respectively. Rates of serious AEs remained low in both groups (overall: 4.06; RDTN: 3.70), as did rates of serious infections (overall: 1.37; RDTN: 1.24), injection-related reactions (overall: 7.38; RDTN: 7.16), and malignancies (overall: 0.31; RDTN: 0.38). Notably, no heightened risk in any of these safety outcomes was observed over time.

Laboratory parameters remained largely stable over the observation period. Mean immunoglobulin G levels held steady through 7 years of treatment, while mean immunoglobulin M levels declined initially before stabilizing above the lower limit of normal. Mean lymphocyte and neutrophil counts were also stable and consistent with baseline values. Updated 8-year data, with a data cut off of September 25, 2025, are being presented at the AAN conference at which this abstract was submitted.

“The 8-year results will provide further insights into the long-term safety of ofatumumab in people living with relapsing MS (plwRMS) including RDTN plwRMS, supporting informed clinical decision-making,” first author Gabriel Pardo, MD, the founding director of the Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, and colleagues wrote in the abstract.¹

Earlier this year, data from AGNOS, an 18-month, phase 4 trial (NCT05084638) showed that treatment with ofatumumab led to effective reductions on biomarkers of neuroaxonal damage in patients with relapsing-remitting multiple sclerosis (RRMS).² The data, which were presented at the 2026 Americas Committee for Treatment & Research in Multiple Sclerosis (ATCRIMS), held February 5-7 in San Diego, showed that mean serum NfL levels in the ofatumumab group declined from 20.66 pg/mL at baseline to 10.54 pg/mL at month 6 and remained stable at 11.05 and 10.20 pg/mL at months 12 and 18, respectively. In healthy controls, sNfL levels were lower and relatively stable over time, measuring 7.96 pg/mL at baseline and ranging from 8.03 to 9.29 pg/mL through month 18.

Ofatumumab was approved for the treatment of MS in 2020. Late last year, NeurologyLive® spoke to Riley Bove, MD, an associate professor of neurology at the University of California, San Francisco, about the evolving role of ofatumumab in MS treatment since its approval.

“Since its approval, ofatumumab has become one of the mainstays of B-cell–depleting therapy,” Bove told NeurologyLive. “One of its distinguishing features is that it’s given as a subcutaneous injection that patients can self-administer at home, in contrast to infusion-based therapies. That convenience has been important for many patients.

“We now have data showing ofatumumab’s effectiveness as both a first-line therapy and as a switch therapy, as demonstrated in the ARTIOS study. We’re also seeing emerging data about its use around pregnancy and lactation. Across all these studies, ofatumumab continues to demonstrate high efficacy, and we haven’t observed new safety signals beyond those identified in the initial trials.”

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REFERENCES
1. Pardp G, Montalban X, Cohen J, et al. Ofatumumab treatment up to 8 years shows a favorable and consistent safety profile in people living with relapsing multiple sclerosis. Presented at: 2026 American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. Hendin B, Wray S, Chinea A, et al. P067 / P067 - Effect of Ofatumumab on NfL and GFAP Levels in Treatment-Naïve Patients With Early Relapsing Multiple Sclerosis: Results From the AGNOS Study. Presented at: 2026 ACTRIMS Forum; February 5-7; San Diego, CA. ABSTRACT P067.