Role of Evusheld in Preventing COVID Infections in Multiple Sclerosis

Svetlana P. Eckert, MD

Evusheld (AstraZeneca), a combination of tixagevimab and cilgavimab, was FDA approved for the emergency use for treating the pre-exposure prophylaxis of COVID-19 in certain adults and pediatric patients. Patients with neuroinflammatory diseases who are treated with potent immunosuppressive therapies are shown to be at higher risk of more severe COVID-19 outcome and have significantly reduced seroconversion after routine SARS-CoV-2 vaccination.¹

Recently, at the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 23-25, in San Diego, California, a poster presented data on real-world efficacy of Evusheld in preventing breakthrough COVID-19 infections in immunosuppressed patients with neuroinflammatory diseases.¹ A total of 31 patients were followed for six months after administration of Evusheld, with findings showing a significantly reduced number and severity of breakthrough COVID-19 infections during the Omicron wave.

Svetlana P. Eckert, MD, clinical assistant professor of neurology at Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, New York sat down with NeurologyLive® at ACTRIMS to discuss the findings in detail. She provided an overview of the study and the motivations behind conducting it, as well as herher initial reactions to the results. She explained the significance of these findings, and how the study investigators plan to build upon this research in future studies.

NeurologyLive®: What were the reasons for conducting this study?

A lot of our patients with MS are on immunosuppressive medications. Some of them suppress the immune system more than others so it was really important, especially at the beginning of COVID pandemic, to protect those patients from severe COVID disease. But we know—and there's more and more evidence coming out—that there's certain patients on stronger immunosuppressive therapies such as S1P inhibitors, and B-cell depletion therapy, who ended up not mounting response to the COVID vaccines. Evusheld helps prevent infection in some of those patients and had been approved to do so. We started using that clinically, but we really wanted to figure out how we can improve the response to the vaccines and whether the spike antibody positivity affects clinical outcomes. We looked at patients 31 patients who received Evusheld and 126 control patients, some of which were seronegative for the antibodies. Those patients who did not receive Evusheld had a much higher rate of infection with COVID. Breakthrough infection was 34% in that group, as opposed to only 6% in the patients who received Evusheld.

How significant are these findings considering several patients will use immunosuppressives frequently?

It is extremely significant because a lot of times, even today, they were talking a lot about the timing of immunization with the cell-depleting therapies, which is very important. Are you going to wait for those six months after the last ocrelizumab infusion? Or can you do something to protect the patients in the meantime? One of the best ways to do this seems like it's going to be Evusheld or something similar in the future. Also, the patients that did end up having breakthrough COVID infection—2 out of the 31—also had relatively mild disease. There were a much higher rate of severe or moderate COVID infection in the group that did not receive Evusheld.

How does the use of Evusheld potentially reduce the risk of exacerbations of MS related to vaccination?

There's a few points to that, number one: instead of asking the patient's body itself to produce the antibodies, we are providing the antibody that would mark the virus for destruction earlier, and potentially prevent the spread of infection from the nasal passages to the rest of the body that could contribute to the development of more severe COVID. The other thing that is helpful mechanistically in this case is that when you give Evusheld, it is it passive immunization that is being provided to patients. It’s not like the patients develop an antibody response or that their immune system goes into overdrive. There's much less potential to cause any possibility of pseudo exacerbations or even true exacerbations of MS related to the vaccination itself.

Can this approach be applied in other neurological disorders?

It's important to mention that Evusheld is approved as emergency use authorization for the treatment or providing immunity protection against COVID to patients across the board who are immunosuppressed. It was not specifically approved for patients with MS alone. Unfortunately, it now seems to be less effective against the newer COVID variants. We primarily conducted our study during the time of the omicron variant, which clearly still makes a difference. But I think that the future is going to be working on a similar medication that would provide immunity for patients with newer variants. The manufacturer is definitely working on that actively, as there’s a study that is in the works called SUPERNOVA. We look forward to working on that and looking at some results of those studies.

What does the future hold for passive protection of patients against COVID-19 and what steps need to be taken to provide it?

I think that one of the things we need to work on is educating that this medication is out there. For the susceptible patients with MS, it's going to be a game changer in a way because if patients don't respond to a vaccine, then what is the next step? Right now, because I mentioned it was emergency use authorization, it was withdrawn in January of this year because it's no longer seems to be effective for some of the variants of the spike protein. Right now we don't have any passive protection for the patients. We need to hurry up and catch up with the COVID variants and provide this for our patients.

Transcript edited for clarity.

Click here for more coverage of ACTRIMS 2023.

REFERENCES
1. Eckert S, Jakimovski D, Mirmosayyeb O, et al. Tixagevimab and Cilgavimab: Evusheld Prophylaxis Prevents Breakthrough COVID-19 Infections in Immunosuppressed Population: 6-Month Prospective. Presented at ACTRIMS Forum 2023; February 23-25; San Diego, California. Abstract P120.