What Is Known About COVID-19 Vaccine Response in MS


News Network | <b>Consortium of MS Centers 2022: News Network</b>

Daniel Kantor, MD, discussed his presentation at the 2022 CMSC annual meeting on COVID-19 vaccine response in patients with multiple sclerosis who are being treated with sphingosine 1 phosphate receptor modulators.

WATCH TIME: 6 minutes

For more coverage from CMSC 2022, click here. A transcript of the conversation is below.

Matt Hoffman: I'm here with Dr. Daniel Kantor, sitting down at CMSC.

Daniel Kantor, MD: Thank you for having me.

Matt Hoffman: I want to talk a little bit about a poster you're presenting on COVID-19 vaccine response on patients treated with ozanimod (Zeposia; Bristol Myers Squibb) and other S1P receptor modulators. To start from a point if you weren't familiar with the work—abroad overview, how did we get to this point? What prompted this study?

Daniel Kantor, MD: What prompted the study is this virus called coronavirus.­­ The novel coronavirus-19 and the COVID-19 pandemic made a lot of questions for the MS community. The first question was, is the MS community more at risk? And the next question is, once there was a vaccine, what does that mean in terms of vaccine response?

For the first question, it looks like overall, people with multiple sclerosis are not more at risk than other people with other autoimmune diseases or frankly, with other conditions in general. People on certain medications may be at a higher risk, and one of the things we noticed is that when you deplete or push down the B cells—well, B cells are important in in response to viruses in response to vaccines. There are very popular medications we use now in multiple sclerosis or ocrelizumab (Ocrevus; Genentech), we use ofatumumab (Kesimpta; Novartis), and some people are still using off label rituximab (Rituxan; Genentech/Biogen). It looked like those people had more severe COVID-19, perhaps more intensive care unit visits, and so then, the question was overall, if you give a vaccine, would they have the same responses as it would in somebody without multiple sclerosis not on any of those medicines.

The first part of that question is that a lot of us around the world scrambled to try to answer that. Some people, what they did is they looked back at their patients, and they looked at case series, and they said, “Well, these people were on these medicines, and they got the vaccine, how many of them got COVID,” et cetera, et cetera. There are obviously problems with that kind of design. What we designed was a prospective study. The prospective study was looking at people who were in anyway choosing to get the vaccine because not everyone chose to get the vaccine. But in anyway choosing to get the vaccine, and then the question is, well, if we look at your immune markers beforehand, your lab markers beforehand, your questionnaires beforehand, and then after you get the vaccine and after you get the second shots, what happens when we follow those people out for the rest of the year?

The way it was designed was actually to look specifically at one of the novel S1P receptor modulators. Many people remember the legacy S1P receptor modulator, and it was unselective, this medicine Gilenya, or fingolimod. There have been questions and other people’s studies that suggested that well, it doesn't just look like B cells are a problem, it looks like if you sequester the immune cells inside the lymphoid organs, then maybe that's not good for that vaccine response. But maybe it's different when you don't have an effect on S1P4. When you think about ozanimod, it's selected for S1P1 and S1P5—these two receptors, but not S1P4. Because of that, it might be that we see some sort of different response. So, we wanted to test that.

The primary end point of the trial is to look at the vaccine response. So, have they had a change in their immunoglobulin response to the spike protein, and has it happened 4 weeks after the second vaccine. We have the data, it's fresh, that's why it's late breaking here. The data shows us that yes, actually, when you gave it to people with ozanimod, 100% of the people actually went ahead and had the response.

Then we look in the poster at other questions, we looked at other disease modifying agents also. I would have loved to do the study where we actually have 30 subjects for patients in each arm for each disease-modifying agent—but we’re blessed in MS. Now there's more than 20—depends on how you count them—disease-modifying agents. So, we looked at 30 on ozanimod, and we looked at 30 at all other comers. When looked at the other 30, what we saw is if you ignore the 1 patient who was on fingolimod and then the 3 patients on ocrelizumab, then yes, those people also had a really good response. When you looked at the people—and I don't want to make conclusions about 1 and 3 patients, it's very hard to make any—but overall, the primary end point was really about ozanimod, and that actually did show an immune response.

Now, we didn't just look at the immune response, we looked at the quantitative the number of immune responses. What's interesting is the numbers are still protective. They're a little lower than other medications. So, a little lower than people who are taking glatiramer acetate (Copaxone; Teva), or the beta interferons, for example, but they're still protected. Then we also looked at T cell markers. Now the problem is, to do a really good T cell study, you need fresh samples. This study was distributed across the United States, the idea was to get virtual enrollment, and we send phlebotomists to people's homes. We couldn't necessarily send it to one of the very scientific labs that do amazing jobs at T cell response. But there is a company called Adaptive Biotechnologies that got an EUA—emergency use authorization—to look at T cell response in a binary fashion: yes and no. It was made not for vaccine response, actually for whether you were infected with SARS-CoV-2 (COVID-19) or not, but many of us use it to also look at vaccine response. Remember, we're not getting a gradient of response, we're really just getting a yes versus no. Even though the patients on ozanimod had a lower, still protected, but a lower antibody response, they still have protective T cell responses. That was what was significant about this study.

Transcript edited for clarity.