Comparing Mechanisms and Advantages of MS Medication Ofatumamab

At the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, new findings on ofatumumab (Kesimpta; Novartis) drew significant attention for their implications in relapsing multiple sclerosis (MS). Among them were results from the ARTIOS trial, which evaluated patients switching from fingolimod or fumarate-based therapies after breakthrough disease, showing striking reductions in both relapses and MRI activity. In addition, long-term extension data reinforced the durability of ofatumumab’s efficacy and safety profile, underscoring its role as a central B-cell–depleting therapy in the MS landscape.

In this NeurologyLive^® Special Report mini-series, Riley Bove, MD, an associate professor of neurology at the University of California, San Francisco, breaks down the latest evidence and shares key takeaways for clinical practice. Across four short episodes, Bove explores how ofatumumab differs from other therapies, interprets the new ARTIOS results, reflects on its evolving use since approval, and looks ahead to the questions still shaping MS treatment research.

In episode 1, Bove outlines how ofatumumab’s mechanism as a B-cell depleting therapy differs from oral disease-modifying treatments such as fingolimod and fumarates. She explains why eliminating circulating B cells can yield highly effective disease control compared with immunomodulation approaches. The discussion also highlights practical considerations, including administration differences and the implications for long-term treatment planning.

Transcript is edited for clarity.

Riley Bove: Ofatumumab is a B-cell–depleting medication. It’s a monoclonal antibody, and the antibody targets a component on the surface of B cells. By doing that, it effectively eliminates the B cells from circulation.

B cells are a subset of immune cells, a type of lymphocyte. While we don’t think B cells are the ones directly causing the damage in MS, we do believe they play more of an “activating” or “cheerleader” role in the disease process. We’ve seen that when we deplete B cells, patients tend to do very well.

So, a B-cell–depleting therapy is quite different from the oral medications—such as fingolimod or fumarates—in that it is considered a highly effective option. It’s encouraging that we can now have these conversations about multiple therapeutic mechanisms and approaches, which is a testament to how far MS treatment has advanced.