COMMENTARY

The Latest on Multiple Sclerosis and COVID-19 Vaccines

Stephen Krieger, MD

Disclosures

September 23, 2021

This transcript has been edited for clarity.

Hi. I'm Dr Stephen Krieger from Mount Sinai in New York, reporting for Medscape on the current approach to treating patients with multiple sclerosis (MS) in the evolving COVID-19 pandemic, particularly as it relates to vaccinations and booster shots.

I'm recording this about a year and a half into the COVID-19 pandemic in the United States. During that time, we've learned a lot about how this disease affects people with MS. The principal takeaways have been that people with MS are not more vulnerable to COVID-19, though patients who are older, more disabled, and have more comorbidities certainly are.

We've also learned that our disease-modifying therapies do not profoundly increase the risks associated with COVID-19, although patients on higher-potency medicines may have an increased risk for mortality from COVID-19. That difference, we believe, is quite small.

For the most part, we've been counseling all of our patients in the same way with respect to maintaining COVID precautions during times and in regions of increased transmission and prevalence, irrespective of what type of disease-modifying therapy they're on.

Vaccine Efficacy and Response in Patients With MS

The National Multiple Sclerosis Society put out a position statement strongly advocating for MS patients to take one of the authorized vaccines for COVID-19. We've strongly encouraged our patients to get vaccinated to protect themselves from the disease. With the increasing surge of the Delta variant in the United States, that has taken on even greater importance as we try to protect the MS community.

Vaccines have been available for 6 or so months in the United States, and we've learned a bit about how our disease-modifying therapies may impact their efficacy. There was a study done out of Israel by Achiron and colleagues that found there was decreased rate of antibody production after vaccination of MS patients treated with both B-cell–depleting agents and oral sphingosine-1-phosphate (S1P) modulators.

It's not terribly surprising that B-cell–depleting agents would decrease the level of circulating postvaccine antibody; however, it was something of a surprise that the S1P modulators seem to have a similar effect, at least in this study. What these agents have in common is that they both decrease circulating numbers of B cells: depleting them for anti-CD20 and blocking their movement out of lymphocytes into circulation for the S1P modulators. So, it may be the case that the absence of circulating B cells is sufficient to blunt the antibody response after COVID-19 vaccination.

What we don't know, however, is the extent to which the antibody response to the vaccination truly is an indicator of its efficacy.

There is emerging data that the vaccines work not just through antibody production but through T-cell pathways as well. Work from Dr Amit Bar-Or's laboratory at the University of Pennsylvania, currently available on a preprint server and forthcoming in the peer-reviewed literature, looked at both B- and T-cell responses after the mRNA vaccines in patients treated with anti-CD20 agents. They found that although there was a significant attenuation of antibody response in the anti-CD20 population, the T-cell response, both CD4 and CD8, was extensive. This indicates that even in the absence of demonstrable postvaccine antibodies, there may be a robust immune priming that occurs. That offers a bit of reassurance to patients who have been on anti-CD20 agents for MS, received one of the COVID vaccines, and did not mount an antibody response.

We'll be presenting data from Mount Sinai at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress in October, which will share our experience with disease-modifying therapies and postvaccine antibodies. That will have similar findings about the attenuation of antibody response in patients on anti-B-cell therapies.

Who Should Receive Boosters and When?

A current topic of much interest when it comes to the timing of vaccines is the use of boosters. In early August, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) granted an extension of the authorization for emergency use of the vaccines to allow for booster doses in patients deemed immune compromised or immune suppressed.

Based on the data that I previously described, we are viewing patients on the cell-depleting MS therapies, as well as the S1P modulators, as falling into that category of being immune compromised and meriting a booster dose of one of the mRNA vaccines. I expect that the National Multiple Sclerosis Society will put out a statement to that effect as well. The takeaway point will be all patients with MS being treated with S1P modulators, anti-CD20 B-cell–depleting therapies, and other high-potency treatments that deplete immune cells (eg, alemtuzumab or oral cladribine) should receive a booster vaccine for COVID.

Then the question becomes, how can we properly time those boosters? For therapies given infrequently, such as the every-6-month infusions of anti-CD20 agents, the recommendation is going to be, whenever possible, to time the booster dose 3 or 4 months after their last infusion. That timing may not always be possible, but the rationale for it is that allowing for some degree of B-cell reconstitution may maximize the likelihood of the vaccine's generating an immune response. But in areas with very high prevalence of the Delta variety of COVID, it may be even better to get vaccinated sooner rather than waiting the requisite 3 or 4 months after the last round of anti-B-cell infusion therapy.

It will become a personal decision, but the takeaway is going to be that those patients on our higher-efficacy MS therapies should get a booster vaccine, which is in line with what the FDA and the CDC has allowed. We want to try to optimize the timing to maximize the likelihood that the vaccine will be successful. In the meantime, we urge patients, particularly those in areas of high COVID prevalence, to maintain the sorts of precautions, such as masking and distancing, that we have become all too familiar with over the past year and a half.

The science will continue to evolve. I expect there'll be more information after the ECTRIMS congress in October, which I expect will be very focused on the intersection of the pandemic with the MS community. We'll certainly return with more updates then.

For Medscape, and Mount Sinai in New York, I'm Stephen Krieger.

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