#MSCOVID19. Learning from arthritis….Anti-CD20 antibodies block vaccine responses

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We have seen one paper in MS…this is going to be repeated…Why because they use anti-CD20 (rituximab) in MS. In arthritis they are seeing blunting too.

Spiera et al. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases .http://dx.doi.org/10.1136/annrheumdis-2021-220604

There is a paucity of data on the effect of antirheumatic drugs on serological responses to COVID-19 vaccines. Anti-CD20 therapies deplete B-cells, with reconstitution often not beginning for 6–9 months after infusion, resulting in diminished humoral immune responsiveness…… serological response to vaccination was assessed using a semiquantitative anti-SARS-CoV-2 enzyme immunoassay…..Vaccination responsiveness was compared between patients receiving various antirheumatic medications. In patients treated with rituximab time between most recent administration of drug and vaccination was recorded. Exposure to rituximab was defined as having ever been treated, however, all patients were within 4.5 years (median (IQR) 0.70 (0.41–1.74)) years of last exposure. B-cell reconstitution at time of anti-SARS-CoV-2 antibodies measurement was documented, when available, for rituximab-treated patients………Eighty-nine patients met criteria for inclusion. Eighty-three subjects (93.26%) had received both doses of a COVID-19 vaccine at the time of immunoassay. Thirty patients (34%) were treated with rituximab.………A majority of the serologically negative results were among patients using rituximab (20/21)…..Among rituximab users, there was a significant difference in the number of days between those with a positive serological response (median, IQR 704.5 (540–1035) days i.e.= greater than 18 months) compared with those with a negative response (median, IQR 98 (64-164) days = less than 5 months) (p<0.001). B-cell reconstitution was available for 11 patients and there was a significant difference among those with a positive serological response (N=7) compared with those with a negative response, (N=4) (p=0.026).……..Patients who had even weak levels of B-cell reconstitution had higher rates of seropositive responses to vaccines, while B-cell depleted patients invariably demonstrated a negative serological response to vaccination. Importantly, absence of a detectable antibody response to COVID-19 vaccines does not imply absence of improved immunity relative to prior to vaccination in those patients, recognising that other facets of immunity may be enhanced by vaccination.

So this says if you want to make an antibody response it looks like it is better to wait until your B cells start to repopulate, however, this could be a considerably long wait and longer than the 6 months used between typical dosing. Now often in arthrtis they use drugs in addition to rituximab like methotrexate and this may add to the anti-vaccine response. However, will MS be better? I am not holding my breath. We will soon see an avalanche of data saying the same thing. This may give us a clue how long the delay would need to be to get a vaccine response or more likely show us if when you are not likely to respond. However I believe that waiting for 5 months to start just before the next infusion, is not the solution for some people.

So we best get those registries going to find out if people treated with anti-CD20 get re-infected and what happens when this happens. I suspect people will be OK, because people were generally OK when they got COVID-19 before vaccination.

On the plus side there is a reasonable chance you will make a T cell response and we have had examples of people commenting on the blog to say just this. Importantly if you do not make antibodies I believe there are ways to give you protective antibodies. For example the makers of the anti-CD20 MS drugs have anti-SARS-CoV-2 antibodies. Sadly they and the World focused on treating people infected with the virus, generally starting way too late to show any benefit, rather than using it as a prevention against infection. Those studies are ongoing with a different antibody in the UK, it should have been tested on front line health care workers ages and you would have had an answer by now. One trial is called Stormchaser…..maybe this should be done in India.

However, also remember there is a balance and in some instances B cell responses are damaging. We have suggested that prior immune responses to cross-reactive cold-causing coronavirus could be beneficial but in some cases they are damaging

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses McNaughton, A. L., et al. MedRXiv.10.1101/2021.05.04.21256571 

Disclaimer: Please note that the opinions expressed here are those of author and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

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MouseDoctor

11 comments

  • as mentioned on other articles but once again here:
    female 36y 6 cycles OCR with double jab Pfizer after 5m of last OCR dose (0% cd19/20 at time of vaccine)
    antibody outcome (measured twice 3 weeks apart) NEGATIVE
    ELISPOT t – cell test: IfNg 14.0 (SI) and 24.0 IL2 (SI) „significant antigene reaction“
    Lab says it could be a good vaccine reaction (the values are median to high what they have seen) but cannot write it officially as studies are not complete yet.
    so hope for cellular protection (which might be anyway the longer lasting) and so lower probability of severe COVID is there?

    • Yes, this is very reassuring and compatible with data showing the vast majority of pwMS on anti-CD20 therapy deal with COVID-19 very well. Why? It must be their T-cell responses. We are expecting this to happen with the vaccine.

      • We are seeing negative responses in people waiting for 5 months, there are a few weak positives but we are going through the samples.

      • The questions surrounding Ocrevus and vaccine efficacy is so frustrating and scary for those of us taking this DMT. Interestingly, my recent blood work came back with no B cells (last infusion was beginning of December 2020) yet quite a high number of T cells. I hope this is a result of full vaccination (2 doses of Pfizer) about 4 weeks prior and will provide some protection from Covid. As an aside, I imagine combination monoclonal antibodies can be useful in this population since Regeneron did a clinical trial and concluded an 81% efficacy of preventing symptomatic covid in household contacts. If so, lets hope intramuscular shots of this can be approved asap.

  • 47 years/m. 7 cycles of Ocrevus.
    Received vaccinations from Pfizer about 6 months after last infusion in January and February. Infusion of Ocrevus postponed until March. Took an AB test this week: Negative (<21.0 AU/ml).
    Bad news.

    • Not necessarily you probably have T-cell responses to the virus. Some immunity is better than no immunity.

      • Ocrelizumab patient here and antibody negative waiting T cell results. Hoping there are some based on feeling poorly post second jab.
        Question for you fine docs: given the covid risk are you now recommending all your patients who have been on ocrelizumab switch DMTs in order to resume normal activities and reduce risk of a covid induced relapse if the therapy is working on all clinical measures? Or is community immunity close enough to reach such that no change is recommended or needed??

  • I am from Holland where vaccination is well a bit slow. I am 38 and lucky enough to get some Astra they were going to throw away. Question: can i get a dose of ocrelizumab 10 days after my second jab?

    • Ocrelizumab makers recommend 6 weeks in MS
      Rituximab makers recommend 4 weekis in arthritis
      Biology says within about 2 weeks you should have made an antibody response

      I think the current BartsMS view is aim for 4 weeks but anything after 2 weeks this is online on the blog

      p.S> I am not a doctor and am not giving medical advice.

  • I have been on rituximab for 2 years and got my 2 shots starting 18.5 weeks after my last dose (still with 0 B cells). I got an antibody test 2 weeks later which was negative. That same day I took a T cell test and I just got my results today and it came out positive! So I’m pleased 🙂

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