The Potential Need for a COVID-19 Vaccine Booster in Multiple Sclerosis

Joshua Katz, MD

The recently announced COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders trial, initiated by the National Institutes of Health (NIH), will aim to evaluate the effectiveness of an additional dose of the vaccine in immunocompromised patients. Funded by the National Institute of Allergy and Infectious Diseases (NIAID), the trial will include patients with multiple sclerosis (MS), pemphigus, rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis.

Joshua Katz, MD, codirector, Elliot Lewis Center for Multiple Sclerosis Care, assistant professor of neurology, Tufts University School of Medicine; and chairman, Clinical Advisory Committee, New England Chapter, National MS Society, sat down with NeurologyLive to discuss the clinical implications of the trial as experts work to gain more insight as to how to best improve antibody response in this patient population.

While not directly associated with the NIAID trial, Katz shed light on existing data on patients with MS and the variation in vaccine response according to specific disease-modifying therapies (DMTs). While experts have not seen clear differentiation between vaccine type (Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen), according to Katz, bigger issues surround the interaction with different DMTs, namely anti-B-cell therapies and sphingosine-1-phosphate (S1P) receptor modulator drugs.  

NeurologyLive: What insights are you hoping we’ll glean from the NIH trial?

Joshua Katz, MD: It's a really important question because we found that a lot of our patients with multiple sclerosis, depending on their medication, don't make a full response to the COVID-19 vaccines. Then the question is: Are they going to benefit from a booster or not? There are really 2 different questions here. One is whether or not we'll be able to measure an antibody and T-cell response to the vaccine, and then the second question—which is related, but not necessarily the same—is: What's the clinical benefit? Because at the moment, we don't really have a way of directly connecting antibody levels and T-cell function with a level of protection. 

What are the implications and importance for a successful COVID-19 booster for immunocompromised patients and patients with MS?

Of course, for the general population, we're hoping that the boosters provide adequate protection from the Delta variant. So, we need 2 things: we needed to reduce infectivity—which it looks like the current vaccines don't do that good a job of—and then maybe a booster will reduce the potential to spread the disease. Obviously, we want it to provide a higher level of protection because we're now seeing breakthrough cases.

I guess the good news for MS patients is that for the most part, they don't appear to be more susceptible to getting COVID or having more severe infections if they do get COVID. That seems to be true, at least in my population, for patients who are on immunosuppressive medications. The good news is that right now, they appear not to be getting sicker than the average population either if they do get COVID, but we don't really have a lot of experience it with the breakthrough cases. I'm sort of waiting with bated breath to find out if my patients who have been vaccinated, but who didn't have a good response to the first vaccine, are going to show signs that they're more susceptible to breakthrough infections.

What has data shown among those with MS who are vaccinated? Does it differ from vaccine to vaccine?

Well, one of the biggest published studies so far was a paper that came from Israel that looked at patients who were on several different disease-modifying therapies, and their response was only to the Pfizer vaccine. So far, what we've seen in our patients is that it doesn't appear to make a big difference which vaccine they received in terms of their likelihood of making antibodies, although I'll tell you that the numbers between the different vaccines are small, so I can't say that with certainty.

The bigger issue is that certain medications clearly reduce the antibody response to the vaccine, and others don't appear to do that—[that is] the biggest differences among the disease modifying therapies in terms of the response to the vaccines.

How does a patient’s given DMT play a role in their response to the vaccines?

The class of medications that are known as anti-B-cell therapies, which include Ocrevus (ocrelizumab; Genentech), Rituxan (rituximab; Genentech/Biogen), and Kesimpta (ofatumumab; Novartis). Not surprisingly, because they deplete B cells and because B cells are essential for making antibody responses, we've seen that roughly 80% of patients who are on those drugs are not having an antibody response.

Now, we did a small pilot study, where we also check people's T-cell responses, and the good news there is that everybody on the anti-B-cell therapies who didn't have an antibody response, still had a T-cell response. Then the question is, what level of protection does that provide? We still don't have the answer to that, and the hope is that the T-cell response is going to provide adequate protection from severe COVID, but we don’t know.

The other class of drugs that had a big impact on the response to the vaccines, are the S1P modulator drugs, which include Gilenya (fingolimod; Novartis), ozanimod (Zeposia; Bristol Myers Squibb), Mayzent (siponimod; Novartis), and Ponvory (ponesimod; Janssen), and those drugs also have about an 80% failure rate [in making an] antibody response rate in our patients. There, it's actually hard to check the T-cell function because those drugs can lower the lymphocyte count, so it's been difficult to measure, and we have even less information.

Is there anything else that you would like to add?

There's still a lot that we don't know, and I think we're all just hoping that we'll get the information, and it's going to be good news. I'd really like to be able to tell people that getting a booster is going to make a difference in their antibody response, and I don't know yet. 

Transcript edited for clarity.

REFERENCE

NIH launches study of extra COVID-19 vaccine dose in people with autoimmune disease. News release. National Institutes of Health. August 27, 2021. Accessed September 9, 2021. https://www.nih.gov/news-events/news-releases/nih-launches-study-extra-covid-19-vaccine-dose-people-autoimmune-disease