#MSCOVID19 Third Dose Boostsers. A little, I mean only a little better for ani-CD20 but not for fingolimod.

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Apologises for interupting NDG day, but I think it is important news. I know you are all bored with COVID-19 but you have choices to make and therefore you need data. Here is some third dose-booster data (100 using rituximab, 1 ocrelizumab, and 29 fingolimod) and as I have predicted it is not good reading. Although some people who did not make a response after 2 doses made a response after 3, the majority did not. This was the case with fingolimod

The mean time between the last jab of full vaccination and revaccination was 94 days and 78 days (so about 3 months) in patients treated with anti-CD20 and fingolimod, respectively.

Below 70 units was consisdered negative

Higher absolute lymphocyte (regardless of treatment) and CD19-B-cell counts (in patients receiving anti-CD20 therapy) were significantly associated with the development of protective humoral immunity

The most common side-effects were transient local pain and fatigue in both groups. No patients experienced serious adverse effects after revaccination.

What we dont know is the interval between anti-CD20 and vaccination. It is clear that the third dose increases vaccine responses but if you want to optimise this, probably you need a delay. What this all means for infection rate is unknown and it is importance that you do not get disease breakthrough. Remember you make. T cell response with anti-CD20 but not the case with fingolimod with provisos for this.

Given this universally poor response surely it is now time to be stategic to try and optimise the response

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Marton Konig

Efficacy and safety of a third SARS-CoV-2 vaccination in multiple sclerosis vaccine non-responders Konig, M., Torgauten, H. M., Overas, M. H., Chopra, A., Lorentzen, A. R., Tran, T. T., Mjaaland, S., Aaberge, I. S., Myhr, K.-M., Wergeland, S., Berge, T., Harbo, H. F., Torkildsen, O. F. G., Holmoy, T., Celius, E. G., Munthe, L. A., Vaage, J. T., Lund-Johansen, F., Nygaard, G. O. MedRXiv 2021 10.1101/2021.10.15.21264977 —

Importance: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect against coronavirus disease of 2019 (COVID-19) is recommended for patients with multiple sclerosis (pwMS). However, approximately 80% of all pwMS treated with anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod have low or absent humoral immunity after vaccination with two doses of SARS-CoV-2 mRNA vaccines. The efficacy and safety of a third vaccine dose in this group is largely unknown.

Objective: To characterize the humoral immunogenicity and the safety of a third dose of mRNA-COVID-19 vaccine in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity (i.e., anti-SARS-CoV-2 IgG <70 arbitrary units (AU) and <5 AU, respectively) after two vaccinations.

Design, setting and participants: 130 anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination against SARS-CoV-2, received a third dose of SARS-CoV-2 mRNA vaccine. Humoral immunity (i.e., antibody response against SARS-CoV-2) and the frequency and characteristics of side-effects were analyzed in all participants.

Exposures: A third vaccine dose against SARS-CoV-2 with BNT162b2- or mRNA-1273-COVID-19 vaccine.

Main outcomes and measures: Patient- and treatment-specific variables were acquired using a digital questionnaire, the Norwegian Immunization Registry and hospital journals. Humoral immunity was assessed by measuring SARS-CoV-2 SPIKE receptor-binding domain (RBD) IgG response. Low/absent humoral immunity was assumed in cases of AU<70 after anti-SPIKE protein-based serology 3-5 weeks after revaccination.

Results: A third dose of SARS-CoV-2 mRNA vaccine increased anti-SARS-CoV-2 SPIKE RBD IgG levels significantly. The proportion of patients with assumed protective humoral immunity (anti-SARS-CoV-2 SPIKE RBD IgG > 70 AU) were 25% among patients using anti-CD20 therapy and 7% among those treated with fingolimod. No adverse events were registered during the study period.

Conclusion and relevance: A third dose of mRNA-COVID-19 vaccine was associated with significantly increased levels of anti-SARS-CoV-2 SPIKE RBD IgG, and hence assumed protective humoral immunity – in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination. The effect of a third vaccine dose was limited and more prominent among those treated with anti-CD20 therapy.

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MouseDoctor

11 comments

  • Hello MD – Thank you for this post and your timing is great! I’m asking the question to my MS team, 3rd full vaccine (pref a different one to your last) or, booster and sticking to the same?

    My local surgery are not able to help and I await a response from my MS team. I’m conscious that most pwMS on CD20 therapies will be seeking the same answers. From this finding is it still best to get another vaccine booster and hope for the best! Surely, we should have a blood test to check how safe we are – or is too expensive, I hear your say! What about the expense of catching Covid and potentially being hospitalised. It would make more sense just to routinely test us all on immune suppression therapies and then the person will know and can then make a decision to venture out and about more!

    Feeling a bit vulnerable and not sure if I should be going to the gym or cinema. It feels quite normal at the gym – no masks, people not really social distancing (starting to forget – that includes me too :0

    • If you had adeonovirus (JnJ or AZ) for first two doses the preference for third/booster is an RNA for booster, if you had RNA for first two doses then third will be RNA again, moderna gives a higher antibody response than pfizer. The reason for switch to RNA is it induced higher antibody responses.

      Another booster and hope for the best or wait….it is a personal choice…I know what I would do but it is not for me to advise. Your risks of COVID depend on your comorbidities e.g age. As someone with risks, I am cautious and so I want to know if feels normal no masks yes thats why we have 40,000 cases a day:-).

      As for blood test I agree. I would like to know a

    • Dear Jane

      I am very happy that MouseDoctor mentioned our results in his blog and wrote a nice summary. I thought I can try to answer your question from our point of view while we wait for the response from MouseDoctor.

      Your are asking a very good question. In our study (in Norway), we chose to offer revaccination with the Moderna vaccine to the majority of our patients as this type of vaccine has shown to be more effective (mounting an antibody response, i.e., a humoral immunity) in a study published by dr. Sormani (Sormani MP, Inglese M, Schiavetti I, Carmisciano L, Laroni A, Lapucci C, et al. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies. EBioMedicine. 2021:103581.). However, it is important to remember that we still don’t have a clear correlate of protection and we do know that the activation of T-lymphocytes (i.e., cellular immunity) has an important role as well when it comes to overall immunity.

      An other good study from the Bar-Or group in Pennsylvania (Apostolidis SA, Kakara M, Painter MM, Goel RR, Mathew D, Lenzi K, et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat Med. 2021.) shows that despite “poor” antibody production after full-vaccination, the activation of T-cells is quite good in the anti-CD20 group (i.e. rituximab, ocrelizumab).

      I hope this information helps you a bit on the way. I wish you all the best.

      Best regards,

      Marton
      (the corresponding author of the mentioned study)

    • are you getting the usual……from the GP, speak to neuro, from neuro, speak to GP?
      I just spoke to receptionist in neuro who says their pharmacist emailed GPs a MONTH ago telling them that people on Ocrevus et al should be given the 3rd PRIMARY dose. a MONTH for god’s sake!! She also quoted that because I had Ocrevus in early Sept, it has to be 12 weeks after until I can get it in any case.

      She said I couldn’t have a copy of the email because it’s internal only. So, been on to GPs who “will look into it and get back to me” I’m not holding my breath.
      Can’t get the booster instead yet on the online system cos not 26 weeks (22).

      I am SOOOOOOOOOOOOOOOOOOOOO sick of sitting in the house afraid to go out. (I did have an MS nurse tell me at end of Aug to get out and about + meet up with family and friends and I am at no more risk than anyone else) erm helloooooooo 4/5 ocrevus users have made no immune response to covid vax

      Why does everything medical have to be so hard?
      I wouldn’t go anywhere near a gym, all that hard breathing in and out. #covidIsAirborne

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