Vaccination-safe disease-modifying treatments

V

Long time, no COVID posts but today we have

Achiron A et al. Ther Adv Neurol Disord. 2021 14:17562864211012835. doi: 10.1177/17562864211012835.

Groups is Israel were first to report on the effects of two doses of COVID-19 vaccine. They showed that CD20 depleting antibodies and fingolimod inhibited the antibody response. This led to the suggestion by some that it may not be worth vaccinating people with MS. However, this view was questioned and this was rather supported when they looked at T cell responses as the vaccined made T cell responses.

Achiron A. Humoral immune response in multiple sclerosis patients following PfizerBNT162b2 COVID19 vaccination: Up to 6 months cross-sectional study. J Neuroimmunol. 2021;361:577746. doi: 10.1016/j.jneuroim.2021.577746

It was also seen that there was a T cell response with ocrelizumab, but not with fingolimod. So why is it suggested that that CD20-depleting antibodies may increase symptomatic disease (possibly invloving hospitalization), whereas this is not the case with fingolimod. Because as fingolimod was blocking T and B cell responses this should lead to worse outcomes, but it doesn’t.

So Interesting question. I dont have the answer.

However, maybe they simply did not look hard enough to see if fingolimod was worsening outcomes after COVID-19 infection. In the study showing worse outcomes after infection in vaccinated people treated with fingolimod and ocrelizumab they looked at information from 19,000 people (see below). To see worsening there has to be enough events of worsening if you look at 19,000 people and the risk is say 1% you see 190 people with infection if you look at 190 people you may see 1 or 2, which is too low to make a call. If we look at the numbers of people in the studies before this study they contained about 2500 people and they contain more people taking ocrelizumab than fingolimod so it will be easier to see a problem with ocrelizumab than fingolimod. It was shown that the antibody response wanes so there was a need for a booster.

This group were not the first to report what happened after the third dose? There was a greater response but data was not reported for ocrelizumab and fingolimod as they apparently were not deemed “vaccination-safe”.

So it is interesting that vaccination is coming into the MS drug vocabulary and the question is whether this will influence choice of treatments? Moving forward what do you think?

At the moment we get annual flu vaccines maybe COVID top-ups will influence your choice of treatment.

COVID-19 vaccination in patients with multiple sclerosis: Safety and humoral efficacy of the third booster dose.Dreyer-Alster S, Menascu S, Mandel M, Shirbint E, Magalashvili D, Dolev M, Flechter S, Givon U, Guber D, Stern Y, Miron S, Polliack M, Falb R, Sonis P, Gurevich M, Achiron A.J Neurol Sci. 2022 Jan 21;434:120155.Background: As immunity against SARS-COV-2 wanes following first and second doses of vaccination, a third dose is administered in several countries around the world. Similarly to the first doses, risks related to vaccination and humoral immune response in patients with multiple sclerosis (MS) need to be assessed.

Objective: Characterize safety and humoral immune response following the third dose of COVID-19 vaccination in a large cohort of MS patients.

Methods: We assessed the safety of the third dose of the BNT162b2-COVID-19 mRNA vaccination in adult MS patients and evaluated SARS-CoV-2 IgG response.

Results: Two hundred and eleven adult MS patients received a third dose of BNT162b2 COVID-19 vaccination. Median follow up time was 66 days from vaccine administration (IQR 54-84). The frequency of any adverse event was 54.5%, with the most common reported adverse events being fatigue, local pain at the injection site, fever and muscle or joint pain. Transient increase in MS symptoms was reported in 3.8% of patients, none of them requiring treatment. The rate of acute relapses treated with IV steroids was 3.3%. In a sub-group of 55 patients, 20 untreated and 35 treated with vaccination-safe disease-modifying treatments, SARS-CoV-2 IgG levels increased 21-fold (median ± SD 21.6 ± 53.05).

Conclusions: The third dose of COVID-19-BNT162b2 vaccine proved safe for MS patients, with no increased risk of relapse activity. Untreated patients and patients treated with vaccination-safe disease-modifying treatments show significant increase in SARS-CoV-2 IgG levels following the third dose of vaccination.

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MouseDoctor

9 comments

    • Yes there is a study supported by Novartis but they havent released the data, they presented it at ECTRIMS last year and it was half-way between good and not so good response, maybe better than fingolimod but maybe the same, the size was too small at the time. I beieve they are planning to release the info at an MS meeting….by which time it will be too late for any body to care….maybe it is the plant. If there is no mud to throw it cant stick, but I imagine it gets tarred with the fingollimod-brush because you would think they would want the info in the public domain if there was a good response

  • Thanks Dr Mouse. If someone changed off fingolimod to another DMT that doesn’t impact vaccine response, is there any info on how long fingolimod effects on poor b/t cell vaccine response last? longer than the drug wash out?

    • Unlikely once it has washed away but sometimes there is long term reduction in white bllood cells, which could be abit of time

  • Hello MD- ‘been trying to figure out a way to answer the question. You ask (I think) for reader opinion whether DMT effect on vax effectiveness might influence DMT choice. The variables are all over the place and I won’t start listing them here. But the new MSr only wants to be “cured”, and talk or learn about little else. The longer term MSr might know that opting out of Ocrevus treatment (for example), offers a range of futility in the near term so if you’re “in it”, you might as well stay in. It’s a mess with no help from Roche. (That’s nice of them.) Lots of questionable ethics flying around, in my opinion. Being newly diagnosed, I’d want to stop the MS no matter what and would (if I were younger) probably overlook covid and the flu and go with the strongest thing I could get my hands on (here in the US), even if it were carefully and forcefully drilled into me about the smoldering reality and the covid risks.

    What’s the risk? Increased risk of infection and reinfection and reinfection and all that might mean in terms of relationships, employment, and other acquired long term personal health issues. That doesn’t include the next unknown variant. It also doesn’t include whether I live in Texas or New Jersey and if people around me care. It’s a mess.

  • I wish there was a way to get T-cell data outside of studies like this. I finally made a normal antibody response after my third shot despite being on fingolimod and I’d love to know where that leaves me t-cell-wise.

  • Can you please correct the following sentences from your text so that they become clearly understandable? Thank you!!
    So why is it suggested that that CD20-depleting antibodies may increase severe [???] whereas this is not the case with fingolimod.
    However, maybe they simply did not [???] hard enough and perhaps fingolimod is used less than ocrelizumab so it (??) took longer to show itself(see below)

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