#MSCOVID The Third Jab…The news doesn’t get better for the problem treatments

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Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis on Ocrelizumab or Fingolimod.
Palomares Cabeza V, Kummer LYL, Wieske L, Hagen RR, Duurland M, Konijn VAL, van Dam KPJ, Stalman EW, van de Sandt CE, Boekel L, Verstegen NJM, Steenhuis M, Rispens T, Tas SW, Wolbink G, Killestein J, Kuijpers TW, van Ham SM, Eftimov F, Brinke AT, van Kempen ZLE; Target-to-B! (T2B!) SARS-CoV-2 study group.Neurol Neuroimmunol Neuroinflamm. 2022 May 6;9(4):e1178.

Objectives: To evaluate whether a third vaccination shows an added effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell responses in patients with multiple sclerosis treated with ocrelizumab or fingolimod.

Methods: This is a substudy of a prospective multicenter study on SARS-CoV-2 vaccination in patients with immune-mediated diseases. Patients with MS treated with ocrelizumab, fingolimod, and no disease-modifying therapies and healthy controls were included. The number of interferon (IFN)-γ secreting SARS-CoV-2-specific T cells at multiple time points before and after 3 SARS-CoV-2 vaccinations were evaluated.

Results: In ocrelizumab-treated patients (N = 24), IFN-γ-producing SARS-CoV-2-specific T-cell responses were induced after 2 vaccinations with median levels comparable to healthy controls (N = 12) and patients with MS without disease-modifying therapies (N = 10). A third vaccination in ocrelizumab-treated patients (N = 8) boosted T-cell responses that had declined after the second vaccination, but did not lead to higher overall T-cell responses as compared to immediately after a second vaccination. In fingolimod-treated patients, no SARS-CoV-2-specific T cells were detected after second (N = 12) and third (N = 9) vaccinations.

Discussion: In ocrelizumab-treated patients with MS, a third SARS-CoV-2 vaccination had no additive effect on the maximal T-cell response but did induce a boost response. In fingolimod-treated patients, no T-cell responses could be detected following both a second and third SARS-CoV-2 vaccination.

So confirmation of our and other results in that the third vaccination doesnt make many more people seroconvert with ocrelizumab or fingolimod. There is a T cell response from blood cells with ocrelizumab but not with fingolimod. So I think the i is dotted and the t is crossed. Don’t expect much more from the forth vaccination. We have already seen this data from other immunosuppressed conditions. So the big question we have to explain is what is happening with fingolimod. Will the same happen with the other imods…I am predicting they wont be as bad….but let’s see the data.

COI: None relevent except we have reported this already

Disclaimer: These are the authors views and only the authors views

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  • I’m on Ocrevus and I’ve had 5 jabs here in Germany. I’m considered totally unvaccinated based on antibody and T cell cover. Thankfully Evusheld is licensed here in Germany so received that last week. Shame it’s still unavailable in so many countries. For people for whom vaccination is ineffective it is a game changer while it remains effective against current strains. I mean even if it wasn’t as effective as it was pre Omicron it’s still a hell of a lot better than what 5 failed Covid vaccines have offered me.

  • PwMS on Fingolimod here. Today, while having my 4th dose, my face was probably so disappointed that the nurse asked me why I look so sad. I told her my short story with Gilenya and so she asked me “Why are you keep taking doses if this doesn’t work for you or why don’t you switch to another drug?” I really did not have any answers neither my doctor seems to have. Anyone that could help out there? 😞

  • Does the same apply for people treated with these drugs who have had covid 19? I’ve had three vaccines and covid in March, currently considering a fourth jab

  • So what does this mean for those of us taking Fingolimod?

    I have had four Pfizer covid jabs already and have my fifth vaccination (second booster) coming up.
    I have also had Covid in January 22 – when I was given molnupiravir antivirals as well.

    So is life now a choice between taking the risk of going back to normal (but without vaccine protection) or self imposed shielding from Covid, or stopping Fingolimod and then suffering MS rebound and disability?

    My ms nurse specialist and my neurologist offer no support or way forward…

  • Well considering the mechanism of action with anti-cd20s and fingolimod, my guess is it won’t matter how many jabs you give. The result will stay the same. What needs to be changed is medication interval, and finding safe ways to treat MS effectively while still getting decent vaccine responses.

    I know that a T-cell focused covid vaccine that targets more proteins than Spike is being developed, studied and tested in Norway. It will be interesting to see if this will provide better protection for anti-cd20 patients if it gets approved. If not, my guess is that the best way to protect anti cd20 patients in general will be to skip an entire course of treatment and vaccinate at month 11, or to monitor B-cells and vaccinate when protection is expected to be sufficient (>3%?). Vaccinating prior to starting treatment should also be done of course, but covid will mutate anyway so it’ll just be a temporary solution. I also think one should consider other treatments than anticd20 in general in patients who have multiple comorbidities. These are my main takeaways from all the research i’ve seen here.

    • I think it would be interesting to see if a different dosing interval had an impact like it has for some other drugs. I am awre that a dealling dose study is being done with siponimod but it is as if saying nothing about COVID and yoour drug means its not a problem, Int terms of T cell vaccine on anti CD20 …many people taking an anti-CD20 make an adequate T cell response and also getting omicron which most of us will means you get a T cell responses…The interesting think is fingolimod, we essentially know what to do, but neuros are not doing it as the landscape has changed..

      You may have a point vaccinations now take a new place in our thoughts and anti-CD20 will remain a problem that other agents dont have…if you have convenience and efficacy and no vaccine issues then food for thought

      • Good point with the omicron induced T-cells. Natural infection is likely to take care of this aspect.

        I still think anti-cd20 is a great treatment in general, both in terms of general side-effect profile and efficacy. Just look at how (relatively) few people quit anti-cd20 once they’ve started. And I think that after 3-4 cycles of treatment most patients will be protected from relapses for a least a year. Consider the swedish data. Thus, skipping a dose for a vaccine response is probably going to be ok for most people.

        Compare then Lemtrada, which is quite likely to give long-lasting thyroid problems. And then there’s natalizumab with the PML-risk. And Cladribine, which I still don’t believe to be as effective as anti-cd20. So I guess that just as with the other MS-treatments, anti-cd20 will be right for some people and wrong for others. Say you are 50> with several comorbidities. Then I think you should probably take another drug because of the infection-risk and vaccine problems. But for younger patients with fewer comorbidities who do not want to go for the induction-therapies, I think anti-cd20 is still a very good choice.

  • If you have had COVID your vaccination responses are normally much better. but if you have had covid and dealt with it you will deal with it again I am sure. Until vaccinations were reported fingolimod was not reported to cause worse disease so it needs an explanation as anti-CD20 behaved as predicted.

  • I’m not sure if anyone will be able to answer this, my wife is finally almost testing negative after 18 days, I caught Covid from her on day 13 so am still testing quite a strong positive, my question is can I reinfected my wife after she has cleared the virus due to her being B-Cell depleted and not being able to make antibodies, the last thing I want to do is reinfect her after she has cleared it, at the minute I’m wearing a mask around her and sleeping downstairs just incase.

    • I suspect you will be ok…if she has cleared the virus she has enough active cells to get rid of it again it takes a few weeks for the levels to drop and with T cells once they are there they remain

  • I have had 4 vaccines over about 12 months (I am not in the UK and it was partly due to some bureaucracy going on), Covid (Omicron) on top and my immune reaction seems to develop nicely enough. It might be relevant to add that my total count of lymphocytes in circulation has been between 0.7 and 0.9 over the last several years. I am female, turn 59 this August, diagnosed with MS since first noticed clinical symptoms in August 2010 and on Fingolimod since September 2011.
    After the fourth vaccine, values were:
    IgG CMI A – AU/ml = 377.5 and = IgG 2. Unit – BAU/ml = 53.6
    After Covid two months later (Omicron with hardly any symptoms) they were
    3798.0 and 539.9 respectively.
    I saw my values move up over time (afer 2 doses, they were only 162 and 23 respectively and had dropped to very little after six months.
    Interesting, I think.
    The issue probably is that if you are on Fingolimod, you may or may not react to the vaccine – and you do not know in which category you will fall. So I think it would be wrong to tell people not to have the vaccine “because it won’t work anyway”. It just might, at least to an extent.

    • Good point I wish the manufacturers of each drug had tried to optimized as response if they need to.

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