Discussing COVID-19 Vaccinations and Disease-Modifying Therapies in Multiple Sclerosis

Amit Bar-Or, MD, FRCPC, FAAN, FANA

The safety and efficacy of the available COVID-19 vaccines in patients with multiple sclerosis (MS) has remained an ongoing topic of conversation, particularly for those who are on disease-modifying therapies (DMTs). Experts continue to evaluate different aspects of the SARS-CoV-2 virus and resultant vaccinations, with multiple studies initiated to further investigate antibody and cellular responses to vaccines in patients treated with varying DMTs. 

Amit Bar-Or, MD, FRCPC, FAAN, FANA, Melissa and Paul Anderson President’s Distinguished Professor; director, Center for Neuroinflammation and Neurotherapeutics; and chief, Multiple Sclerosis Division, department of neurology, Perelman School of Medicine, University of Pennsylvania, spoke with NeurologyLive following his presentation, “Vaccinations and DMTs,” at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), October 25-28. Bar-Or stressed that experts do not believe that being on any specific DMT poses risks for vaccination; however, there are considerations to be made in terms of maximal vaccine response, which may include patients ensuring their vaccinations are “up to speed” before initiating high-efficacy therapies like anti-CD20s. 

The message, which has been endorsed by the National Multiple Sclerosis Task Force of which Bar-Or is a part, is for patients with MS to get vaccinated, regardless of whether they are taking a DMT or if they are about to start. He provided additional commentary on his separate lecture, “Precision Neuroimmunology in Multiple Sclerosis – Are We There Yet?” outlining the heterogeneity of patients when it comes to perturbations such as immune therapy or a vaccine intervention. 

NeurologyLive: For patients recently diagnosed with MS in the current climate—with COVID-19 still playing a role and available vaccinations—how are decisions about DMTs impacted?

Amit Bar-Or, MD, FRCPC, FAAN, FANA: The important question of how does one advocate and discuss the initiation of new disease-modifying therapies in newly diagnosed individuals living with MS during the pandemic has been informed through some of the emerging data on the impact of certain disease-modifying therapies, or DMTs, on vaccine responses. While we continue to believe that vaccines are important in individuals living with MS, and that there's no added risk of the vaccine in individuals just by the virtue of him or her having MS, we also do not think that being on any of the DMTs pose risks of the vaccination—there are though some contexts in which the DMTs may limit the maximum vaccine response. That is a consideration that we now incorporate into discussions with patients starting new therapies, so that, for example, ensuring that your vaccinations are up to speed prior to initiating certain high-efficacy therapies, and may through the depletion of certain cells, take away from the maximal vaccine response, as well as advocating that people who are on DMTs already consider sometimes the timing of their DMT and vaccination to help maximize the vaccine response.

Looking at the different classes of drugs, what are your thoughts on risks or advantages that those varieties may pose for patients in this climate with the COVID-19 pandemic?

Since the approved COVID-19 vaccines are not in the category of live or attenuated vaccines, there's no risk associated with them in terms of contributing to infection, spreading infection, or causing infection-related complications in individuals who are vaccinated. That's a consideration that is important, especially with certain MS therapies, if the vaccines were live or attenuated. As neither of the RNA vaccines or the viral vector of vaccines that are approved are going to pose any such risk, we don't really think that the vaccines pose any risk with any of the approved MS therapies. It really is more of a question of whether you will mount the maximal vaccine response, not so much a safety consideration.

What would you say is the key takeaway for clinicians when it comes to COVID-19 vaccination the interaction with DMTs?

In terms of the current recommendations—and this is endorsed by the National MS Society Task Force that I've had the privilege of being part of—first of all, individuals living with MS ought to be vaccinated for COVID-19. There is little [evidence] to suggest any added risk by virtue of having a MS in terms of MS and MS disease activity, and while something rarely bad can happen to any one individual, overall, the risks of the vaccines and people with MS are indistinguishable from the general population and the imperative of being well vaccinated in the context of the pandemic is clearly outweighing any risks.

That's true also for individuals with MS on any of the DMTs. There's no risk posed by these vaccines in the context of the DMTs, and so the message to clinicians and patients is get vaccinated—get vaccinated, whether you are on a DMT already or about to go into DMT. Whenever you can get fully vaccinated prior to going on DMTs, that would be a good investment for the future in terms of being able to mount the maximal response, but if you're on a DMT, including a drug like anti-CD20, which will certainly abrogate, if not limit entirely the antibody response to the vaccine, it is not a waste of time to get vaccinated, you still should get vaccinated. We and others have now shown that even those individuals who do not mount good antibody responses—as one would expect in individuals who are B cell depleted—they nonetheless mount very good, and in some cases, even more than the healthy control level of protective T cell responses, both CD4 and CD8, that represent another very important limb of the protective vaccine response against any pathogen, including the COVID SARS-CoV-2.

Is there anything else you would like to add about your presentations at CMSC 2021?

One of the insights that we've gained from the vaccine studies in individuals with MS on disease-modifying therapies, including, for example, anti-CD20, is that it has given us some insights into how immune cells interact with one another inside a human receiving a vaccination. We've learned that when you deplete the B cells, changes in the T cells are informing us on what the B cells and T cells did prior to the B cell depletion. This perturbation of the immune response in the context of a vaccine, in some ways parallels what we do with MS treatments and perturbing the immune response in population of individuals.

We also talked about the importance of understanding the heterogeneity—people not being the same when it comes to any perturbation, be it an immune therapy, be it a vaccine type intervention, and learning how to measure the immune state. How the immune state has changed differently across individuals with these perturbations is giving us now very important insights into how to distinguish who does what, in what context, how to use that information, to perhaps better tailor treatment decisions, choices about what to initiate, what to switch to, when to stop, and so on and so forth.

Transcript edited for clarity. For more coverage of CMSC 2021, click here.