Immunogenicity and Disease-Modifying Therapies


Jeffrey Dunn, MD, and Regina Berkovich, MD, PhD, provide an overview of the impact vaccinations and immunization may have on multiple sclerosis therapies, highlighting the ability of S1P treatments to remain effective.

Jeffrey Dunn, MD: We’ve lived through a historic time since 2019 with the SARS coronavirus COVID-19 infections, for which immunization has been widely recommended, has likely been effective in a historic way. There’s evidence from our colleague Amit Bar-Or in Philadelphia at the University of Pennsylvania and others to suggest that some medications that we might prescribe for multiple sclerosis [MS] can attenuate the efficacy of a vaccination against COVID-19. If a patient had MS and was on therapy and tried to get a COVID-19 vaccination, and had to worry that the vaccination may not be as effective, that’s a haunting concern. Can you take us through your approach to a patient who is trying to do all the right things. They know they have MS, they want to take therapy, but they don’t want to get COVID-19 either and they want to do right by that. What are the issues that come up with these treatments and vaccination and immunogenicity?

Regina Berkovich, MD, PhD: Let’s start with terminology and start with the definition of successful vaccination. Effective vaccination is prevention of severe disease, hospitalization, and death from COVID-19 and the need for excessive therapies like ventilation, special units. If that’s our assessment of the success of the vaccination, then we see that with majority of disease-modifying therapies, the COVID-19 vaccines were successful. But if you understand the success of vaccination from the standpoint of antibody production, in my view, it’s a narrow understanding of the effect of the vaccine. The point of vaccination is prevention of severe disease.

We’ve learned that antibodies alone may not explain the response to the vaccine. Apparently there is a T-cell response. But we don’t know. Maybe there are 3 more mechanisms that we don’t know about. I tell my patients not to rely on the level of antibodies because that can be misleading. We may not know all the mechanisms on how the response to the vaccine is being mounted. Clinical practice is still the best criteria. For example, take the S1P modulators. There was some concern coming from the Israeli study, published by our colleague Dr Anat Achiron, showing that with fingolimod, there might be a low percentage of the antibody production, but what does practice show? Do we see higher mortality with the fingolimod from COVID-19? The answer is no. Do we see the higher hospitalization? No. That should mean that the vaccination was successful in those individuals.

Jeffrey Dunn, MD: Our group at Stanford University did an assessment long term during the pandemic of patients receiving B-cell therapy, looking at their humoral and cellular response. To your point, what we saw was a decreased production of antibodies in response to vaccination, but measurable T-cell reactivity as measured by an interferon gamma release assay was intact. In our limited experience of that cohort we saw them do well clinically. Antibodies don’t equate to immunity. We’ve seen that.

Regina Berkovich, MD, PhD: I agree. Even within that same class—and we keep referring to S1P modulators because it’s fascinating class—it has 4 medications we all actively use, and they’re different. That’s what I tell my colleagues. Whenever I hear, “Why do we need another S1P modulator”—because they’re different. We may see different results with different S1P modulators. We had data coming from Israel on fingolimod, but we’re looking forward to see more data coming from other S1P modulators.

Jeffrey Dunn, MD: It’s an ongoing investigation. One more question in this module. We know that immunogenicity is important. It’s going to be important for COVID-19 and potentially also for future vaccinations. We know that different disease-modifying therapies appear to have different profiles and different impacts on immunogenicity. Are there certain concerns you have, or are there certain medications that are FDA approved for MS that you would favor or that you might find yourself staying away from, in a patient you’d consider high risk of developing COVID-19 who needs the full benefits of vaccination?

Regina Berkovich, MD, PhD: We’ll need to look into the clinical reports from the countries with the highest mortality rates, such as Italian experiences, and see what they reported there. I would see some concern with the less reversible longer-acting B-cell depleters.

Transcript Edited for Clarity

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