The writing was on the wall for fingolimod…But it was written in invisible ink:-( The destiny of vaccination responses.

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When I was an scientific amoeba  beta interferon came along and worked in MS then we had a sea of papers in EAE telling us that beta interferon was immunomodulatory in mice. I thought who cares at that point as you know the answer in humans, why waste animals? Also you could see it was rather rubbish in animals except in the study that used human beta interferons in mice….They should have gone to SpecS|avers before doing a literature review because they would have found out that human beta interferons does not work in mice. so it should had no effect in EAE…so the mouse work was spurious to say the least.

The covid pandemic arrives and we show people with anti-CD20 make a blunted antibody response and guess what? People getting the jab made a poor antibody response. This is not the shocker as it was expected.However, fingolimod was more surprising. There was no indication that there was worsening if you caught covid-19 unlike anti CD20 and in the case reports some antibody response is made in most people…..Now months later after we get the vaccine data that fingolimod is an issue we find out that after covid+19, fingolimod blocks the anti-SARS cov2 response so it should have been predicted.

Easy when you know the answer:-) but.maybe they hadn’t done enough reading as the published vaccine data wasn’t mentioned. Maybe they should have gone to le SpecSavers before doing a literature review. Surprising, mycophenylate was in the medium risk category when it is a risk factor for poor vaccine response in transplantation. I guess that data wasn’t known at the time of submission:-)

Therefore the writing.should have been on the wall and we should know if fingo is the issue or is it a problem with all S1P1 modulators like siponimod, ponesimod, ozanimod. The manufactureres should have got this data my now. If it affects all I can explain it if not I can explain it…..I have been to SpecSavers maybe I am just waiting for the result to be known so I can pretend I guess the right answer all along.

However last year we put our neck on the line to predict the influence of COVID-19 on people with DMT and we suggested you did not need for the neuros to soil their pants.However, taking a bigger look at the reduced vaccine response isn’t that great about half-were negative and samples were taken hundreds of days after infection was enough time for a weak response to be made and disappear. If antibodies were so important why did people taking fingo not have hospitalisation like seemed to occur with anti-CD20. Maybe antibodies are not that important.

Anyway the punch line was that anti-CD20 and fingolimod taking people should get a vaccine. Maybe there is vaccine hesitancy but surely everybody should get a vaccine! . But sadly when they did anti-CD20 and fingolimod are the problem children from an antibody perspective.

I have yet to see fingolimod T cell data. However I have seen data from South America where every one on fingolimod responded to their vaccine. Lets hope this replicates in the countries using this particular vaccine type.

Bigaut K, Kremer L, Fabacher T, Lanotte L, Fleury MC, Collongues N, de Seze J. Impact of Disease-Modifying Treatments of Multiple Sclerosis on Anti-SARS-CoV-2 Antibodies: An Observational Study. Neurol Neuroimmunol Neuroinflamm. 2021 Jul 28;8(5):e1055. doi: 10.1212/NXI.0000000000001055. PMID: 34321333.

Objective: To compare the humoral response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with multiple sclerosis (MS) receiving different disease-modifying treatments (DMTs).

Methods: Patients with MS with coronavirus disease 2019 (COVID-19) and available anti-SARS-CoV-2 serology were included. The primary endpoint was the anti-SARS-CoV-2 immunoglobulin G (IgG) index. The multivariate analysis was adjusted for COVID-19 severity, SARS-CoV-2 PCR result, and the time between COVID-19 onset and the serology.

Results: We included 61 patients with available IgG index. The IgG index was lower in patients with fingolimod or anti-CD20 monoclonal antibodies compared with patients without treatment (p < 0.01), patients with interferon β-1a or glatiramer (p < 0.01), and patients with another DMT (p = 0.01). The IgG index was correlated with the time between COVID-19 onset and serology (r = -0.296 [-0.510; -0.0477], p = 0.02).

Conclusions: Humoral response after COVID-19 was lower in patients with MS with fingolimod or anti-CD20 mAb. These patients could therefore be at risk of recurrent infection and could benefit from anti-SARS-CoV-2 vaccination. The humoral response after vaccination and the delay before vaccination need to be evaluated.

Classification of evidence: This study provides Class IV evidence that patients treated with fingolimod or anti-CD20 monoclonal antibodies for MS have a lower humoral response after COVID-19 compared with patients without DMTs or with another DMTs.

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MouseDoctor

8 comments

    • Actually if you read our first covid-19 paper this is the conclusion that we made based on animals studies where you clear the virus before an antibody generates

  • This title and this stream of consciousness intro is very hard to understand. I have no idea what you’re saying with “Now months later after we get the vaccine data that fingolimod is an issue we find out that after covid+19, fingolimod blocks the anti-SARS cov2 response so it should have been predicted.”

    Then the whole post is like “yep now we know it’s bad” followed by “I have yet to see fingolimod T cell data. However I have seen data from South America where every one on fingolimod responded to their vaccine. Lets hope this replicates in the countries using this particular vaccine type.”

    So…we actually don’t know anything we didn’t know months ago? I love and appreciate this blog, but as a person for whom this is life and death, I don’t understand the point of this post.

    • MD’s posts always have this stream of consciousness flavour. It is part of his charm 😉

      Hopefully for most people this question doesn’t even matter as I see no reason why any neuro would still be prescribing mediocre drugs like fingolimod when there are half a dozen higher-efficacy treatments.

      • Well, speaking for myself: There may be half a dozen higher-efficacy treatments NOW, but there weren’t when I started taking fingolimod 10 years ago. And I’m reluctant to switch because (1) the possibility of rebound effects and (2) fingolimod has worked so well for me, there’s pretty much nowhere to go but down (unless we’re talking about something that cures MS or reverses existing damage, of course!) “Higher-efficacy” means it works better for more people, not that it works better for every single person, and since I *know* that I am one of the people for whom fingolimod works extremely well, I’m in a different situation than someone who has to guess how well it would work for them based on the literature (for whom I agree fingolimod would not be the first — or second or third — thing to try.)

  • Excellent article! Thank you for helping to advance my understanding which can only assist in caring for my loved ones. For me, the article was superbly expressed. The content and opinion presented in this blog has contributed immeasurably to the well-being of my family. Over the past several years the heads-up given here on relevant topics has unquestionably helped me provide better healthcare counsel to the most important people in my life. Thank you.

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