Some Clarity Around Multiple Sclerosis and COVID-19

This transcript has been edited for clarity.

Hello. I'm Stephen Krieger from Mount Sinai in New York, reporting for Medscape on the recent European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress held in October 2021.

Unfortunately, ECTRIMS 2021 did not take place in Vienna as originally planned, but instead was held virtually from the comfort of our own homes and offices for the second year in a row. That was obviously due to the ongoing COVID-19 pandemic, which not only changed the setting but really comprised a lot of the content for this important multiple sclerosis (MS) meeting.

I'd like to summarize a little bit of what was discussed at this congress for you.

ECTRIMS Makes a Statement

One key update from the meeting was the release of the ECTRIMS international statement about COVID-19 and risks related to MS. The statement repeated earlier findings that, as a general rule, people with MS don't seem to develop more severe forms of COVID-19 compared with healthy controls. The main factors associated with poorer COVID-19 outcomes in people with MS are similar to those in the general population: advancing age, obesity, comorbid conditions like diabetes, being male, and — in the United States — being Black. Disability itself increased risks for COVID-19 morbidity.

I think we have to be all the more careful with our more physically disabled patients with MS and keep these other risk factors in mind as we treat our patients.

The statement also added that the COVID-19 vaccines are safe for people with MS, which also aligns with the National Multiple Sclerosis Society statement on that topic. We believe that the vaccines are effective for people with MS, although the exception may be for those treated with S1P modulators like fingolimod, and anti-CD20 B-cell depleters like ocrelizumab and rituximab.

That was a big topic at ECTRIMS 2021, trying to figure out the extent to which those medicines change vaccine efficacy, as we'll soon discuss.

Higher Rates of Death in US Patients With MS

Maria Pia Sormani from Italy presented work from an array of COVID-19 registries in MS [this abstract has not posted online]. One thing that she immediately pointed out was the incredible heterogeneity of the data that have been captured internationally in the MS community. For instance, MS death rates from COVID-19 in Italy, France, Turkey, and Sweden were all around 1%. For MS patients in the United States, however, ICU admissions were five times higher and death rates were closer to 3%.

That may reflect some reporting bias, in which more severe cases are more likely to be reported, particularly in the United States, where we don't have a national healthcare system and registry capturing all cases. But it definitely poses a challenge for analyzing cases of COVID-19 and MS.

With respect to our medicines, Pia Sormani reported that the B-cell–depleting agents ocrelizumab and rituximab were associated with a roughly two times higher risk for more severe disease. Rituximab may be the most associated with this, in part because of how long some people with MS have been on it; this is a drug that has been out for a long time. So, duration of treatment with a cell-depleting agent seems to be associated with higher COVID-19 risks.

The other factor that seemed related was the use of intravenous steroids within a month of contracting COVID-19. I think that speaks to our desire to use steroids a little bit more judiciously in the COVID era, and also to be mindful of risks for patients on cell-depleting agents.

Gauging the Effect of MS Therapies on Vaccine Efficacy

In a separate presentation, Pia Sormani shared the Italian experience with the COVID-19 vaccines: the CovaXiMS project. They found strong antibody responses after vaccination with all of the MS disease-modifying therapies — again, except for rituximab, ocrelizumab, and fingolimod, where the antibody numbers were much lower.

Of interest, they found that, across the board, the Moderna vaccine generated approximately a three times higher antibody response than the Pfizer vaccine, which is interesting and may comport with data that we're seeing in the general population.

Achiron and colleagues in Italy had shown similar results that B-cell–depleting agents and S1P modulators like fingolimod decreased the antibody production after vaccination. However, what we don't really know yet is whether antibody levels truly indicate the degree of the immune response after vaccination.

In somewhat analogous work, Apostolidis and colleagues and Amit Bar-Or's group at the University of Pennsylvania provided strong evidence that there is, in fact, immune priming by COVID-19 vaccination in patients, even those treated with anti-CD20 B-cell depleters. They made this conclusion by looking at T-cell responses, which seemed fundamentally normal after vaccination, even in patients treated with B-cell–depleting agents.

We don't yet know how that really translates into vaccine efficacy and resistance to COVID-19. That hasn't been fully explored. Thankfully, there have been very few breakthrough infections on these agents — too few to really draw any conclusions about whether antibody responses are a sufficient indicator of host vaccine immunity. They probably aren't. But of course, there will be more data emerging on that topic.

Anecdotal Experience With Monoclonal Antibodies

I would add from my own experience — and this was not presented at ECTRIMS — that I've taken advantage of the US Food and Drug Administration's approval of the monoclonal antibodies, such as Regeneron's, to treat COVID-19. I've found in my practice that when patients with MS who are on S1P modulators or B-cell depleters receive these monoclonal if they contract COVID-19, it does seem, at least anecdotally, to really attenuate the severity of infection.

We're currently trying to put together the data from ECTRIMS with some that we have available to us in clinical practice. That's the strategy that I've been discussing with my MS patients on immune medicines, certainly in recent months.

That's the executive summary of ECTRIMS 2021, which was very focused on COVID-19. I hope this has served as a practical update for you.

Reporting for Medscape, I'm Stephen Krieger.

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