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ECTRIMS 2021 | COVID-19 vaccination in patients with MS

Maria Pia Sormani, PhD, University of Genoa, Genoa, Italy, discusses the effect of SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis (MS) treated with disease modifying therapies, based on the findings of a large, prospective, multicenter cohort study. Serological assessments were conducted prior to vaccination and 4 weeks after the second vaccine dose to quantify the SARS-CoV-2 antibody response. Analysis of over 1400 patients with pre-vaccine assessment data showed that 11.5% had detectable SARS-CoV-2 antibodies, of whom over 60% were unaware of having been infected. A total of 780 patients had pre- and 4-week post-vaccination assessments, which revealed an 86.8% antibody positivity rate. In line with findings in other countries, patients receiving ocrelizumab, rituximab, or fingolimod had significantly reduced antibody responses compared to patients receiving other DMTs or untreated patients. The time interval between receiving ocrelizumab or rituximab and receiving the vaccine was found to substantially impact vaccine success. Additionally, vaccination with mRNA-1273 elicited greater antibody responses than the BNT162b2 vaccine. Dr Sormani comments on the implications of these findings moving forward. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress 2021.

Transcript (edited for clarity)

We planned a very large study. The plan was to have about 2000 vaccinated patients to be tested with antibody level tests before the first vaccination cycle, and one month after the second vaccination dose. All of them were vaccinated with the mRNA vaccines because in Italy, that was the rule for frail patients. And at the time of the ECTRIMS presentation, we had 1400 patients who had the pre-vaccination test and among them, we found that 11...

We planned a very large study. The plan was to have about 2000 vaccinated patients to be tested with antibody level tests before the first vaccination cycle, and one month after the second vaccination dose. All of them were vaccinated with the mRNA vaccines because in Italy, that was the rule for frail patients. And at the time of the ECTRIMS presentation, we had 1400 patients who had the pre-vaccination test and among them, we found that 11.5% were positive to antibody level detection. This is a very high percentage. I can tell you that the estimate of the people who have been infected in Italy is around 8%, but in this sample, the percentage was much higher.

And interestingly, among those who were positive, that were 165 patients, just 60 of them were aware of having been infected by COVID. So 100, more than 100 patients. So, that is 64% of those who were infected, were not aware of their COVID infection, so they were completely asymptomatic. And this is really relevant because this is a special population, it’s a population of people with a comorbidity, with MS that is a chronic disease. This is also reassuring, telling us that the large of them had COVID without any symptoms, any evident symptoms. So this was, the first interesting result coming out from this analysis.

The results were confirming what was previously observed in Israel, that was the first cohort studied in the world. So, anti-CD20, ocrelizumab and rituximab, patients had reduced antibody levels as compared to all the other drugs and also to untreated patients and also patients on fingolimod. So this result was confirming what was already observed. The interesting results is maybe two-fold. First of all, it seems that rituximab was less impactful than ocrelizumab, but then when we studied the dependency of the antibody levels from the distance between the last drug infusion and the vaccination date, we found that there was a highly dependent relationship. So, I mean the longer, the duration from last infusion to the vaccination date, the higher the antibody levels detected. In Italy while ocrelizumab patients are infused every six months, rituximab patients are infused at longer duration because I mean, rituximab is given off-label, so there’s not a fixed interval between the two doses. So on the average, rituximab patients had much longer interval between the last infusion and the vaccination date. So this may be explains the difference between, between the two anti-CD20 drugs.

Another interesting results is about the difference in the antibody levels between Moderna and Pfizer. Moderna was able to produce a much higher antibody levels than Pfizer, three times higher. That was constant across all the age group, all sex, all the disease modifying therapies. So this can be a relevant observation with clinical implications because, especially for fingolimod patients, for ocrelizumab patients who have low antibody titers, maybe proposing a boost with the third dose with Moderna can help increasing the antibody levels. Of course, all these observation are limited to the antibody levels, that is just one part of the immunity that is caused by the vaccine. So there are other results coming out of cellular immunity that is telling us another part of the story.

And finally, an update that the interesting results is the follow-up of these patients and the incidence of breakthrough infections in fully vaccinated patients. So, if we consider about 1500 for fully vaccinated patients, this is our dominator. In the presentation, I reported nine breakthrough infections. There’s a mistake in the slides just to clarify. But since the day I recorded the presentation to today, we had two additional new cases. So we had the overall 11 breakthrough infection. It is interesting to know that among them six were treated with ocrelizumab, one was treated with rituximab, three were treated with fingolimod and just one was untreated, but with a past history of rituximab treatment. So, all the cases that we detected were in a drug class that was showing lower antibody levels. The good news is that all these cases were mild cases, so no one of them require hospitalization. They develop COVID, symptomatic COVID, but without any severe consequence.

I see what neurologists thinks, and usually they have the tendency to give priority to the therapy for MS. So I don’t think there’s the wish to interrupt the treatment for MS, to minimize the COVID risk or to boost the vaccine efficacy. Of course, there are some rules that can be taken based on this data, for example, delaying as much as possible the vaccination from the time of last infusion in anti-CD20 patients. So maybe delaying two or three months, cannot be problematic, but then you will be able to cause a much higher antibody response that will protect the patients for longer time. And in my view also, vaccinating patients with Moderna can be also, a no cost possible solution for the third dose for these kind of patients. Sometimes it’s not completely practical because it depends on the different hospital, which kind of vaccine they have at their disposal. In Italy, the Pfizer BioNTech is mostly used mRNA vaccine, but anyway, I think this can be taken into consideration for, for the third dose.

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Disclosures

Dr Sormani reports the following disclosures:
Consulting fees from Biogen, Roche, Novartis, Sanofi, Merck, Immunic, Geneuro, and GSK.