Timing Matters: Influenza Vaccination Response in MS Patients on Ofatumumab

Vaccination remains a cornerstone of preventive care for people with multiple sclerosis (MS). But anti-CD20 therapies such as ofatumumab, which work by depleting B-cells, raise a practical question: how well can patients mount an immune response to vaccines once treatment has started?

A new phase 4 study published in Multiple Sclerosis and Related Disorders offers an answer by looking at responses to the inactivated influenza vaccine in patients receiving ofatumumab.

The study enrolled 63 adults with relapsing MS and divided them into three groups. One group received the influenza vaccine before starting ofatumumab, a second was vaccinated at least four weeks after beginning therapy, and a third served as a comparator, vaccinated while on interferon or glatiramer acetate. The goal was straightforward: measure how well patients achieved seroprotection, defined as a protective hemagglutination inhibition (HI) titer, four weeks after vaccination.

Immune Protection Findings

Across influenza A strains, most patients achieved protective antibody levels, though responses were stronger in those vaccinated before ofatumumab. For example, seroprotection against Cambodia and Victoria strains was close to 90 percent before treatment but dipped to 80 percent or lower once therapy had started.

The gap was more striking when looking at seroconversion rates: patients vaccinated after beginning ofatumumab converted less often, with some strains showing rates in the single digits. Those who received the vaccine first, or who were on interferon or glatiramer, mounted more robust responses.

In terms of safety, the influenza vaccine was well tolerated across all groups. Side effects reflected the known safety profile of ofatumumab, with injection-related reactions more common early in treatment. No unexpected safety signals emerged, and most adverse events were mild.

There are a few notable limitations to note here. This was a small study dominated by younger white women, which leaves out older adults who may face more challenges with vaccine response. The trial also stretched across multiple influenza seasons, introducing variability in vaccine strains. Finally, only antibody responses were measured—cellular immunity, which can play a major role in protection, was not assessed.

Why This Matters

For clinicians, the message is pragmatic. Patients with MS who are starting ofatumumab should ideally complete inactivated vaccinations, such as influenza, beforehand to maximize immune response. If that isn’t possible, vaccination during therapy can still provide some benefit, but protection may be less reliable. These results echo current guidance and highlight the ongoing need to tailor vaccine timing in the era of highly effective B-cell–depleting therapies.

Reference
Steingo B, Subei A, Riser E, et al. Immune response to influenza vaccine in patients with relapsing multiple sclerosis treated with ofatumumab: results from an open-label, multicenter, phase 4 study. Mult Scler Relat Disord. 2025;97:106382. doi:10.1016/j.msard.2025.106382.