You have seen the data but you can now read the full paper
We have been examining the B cell repopulation potential from a trial data set, where access was provided by Roche. Thanks for that
If it is the case that a certain level of B cell numbers are associated with a COVID-19 related antibody response after vaccination. we asked how many people on standard ocrelizumab dosing would reach that level at 6 after dosing and then what would happen at 9, 12, 15, and 18 months after the last dose, if there was a drug holiday, remembering the 6 monthly dosing keeps the B cells inhibited.
CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis
David Baker, Amy MacDougall, Angray S Kang, Klaus Schmierer, Gavin Giovannoni, Ruth Dobson
MedRXiv doi: https://doi.org/10.1101/2021.09.26.21264023
BACKGROUND: CD20 depletion is a highly-effective treatment for relapsing multiple sclerosis that maintains B cells at low levels through six monthly dosing of 600mg ocrelizumab. This dosing schedule is associated with inhibition of seroconversion following SARS-CoV-2 vaccination, in contrast to the high levels of seroconversion following treatment with alemtuzumab and cladribine tablets. A number of emerging reports suggest that repopulation of 1-3% B cells facilitates seroconversion after CD20-depletion. The frequency of this occurring following repeated ocrelizumab treatment, after other DMT, and after treatment cessation is largely unknown.
METHODS: Relapse data, lymphocyte and CD19 B cell numbers were extracted from phase II ocrelizumab extension study (NCT00676715) data supplied by the manufacturer via the Vivli Inc, trial data-request portal. Repopulation data of oral cladribine from the phase III CLARITY study (NCT00213135) was supplied by the European Medicines Agency; and the alemtuzumab phase III CARE-MS I (NCT00530348) and CARE-MS II (NCT00548405) trial data were supplied by the manufacturer via the clinicalstudydatarequest.com portal.
RESULTS: Only 3-5% of people with MS exhibit 1% B cells at 6 months after the last infusion following 3-4 cycles of ocrelizumab, compared to 50-55% at 9 months, and 85-90% at 12 months. During this time relapses occurred at consistent disease breakthrough rates compared to people during standard therapy. In contrast most people (90-100%) exhibited more than 1% B cells during treatment with either cladribine or alemtuzumab.
CONCLUSIONS. Few people repopulate peripheral B cells with standard ocrelizumab dosing, however an extending the dosing interval by 3-6 months may allow many more people to potentially seroconvert in the relative absence of excess relapse-activity. Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. This may help protect against severe COVID-19.
This paper may help you to decide what you are going to do. Remember it is an un-peer-reviewed paper. It has been submitted for such review
David Baker, Amy MacDougall, Angray S Kang, Klaus Schmierer, Gavin Giovannoni, Ruth Dobson Seroconversion following COVID-19 vaccination: Can we optimize protective response in CD20-treated individuals? Submitted for publication
Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence the severity of COVID-19. There has been increasing concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following natural SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. This may be optimized in the anti-CD20-treated population by vaccinating prior to treatment onset or extended-interval/delayed dosing in those established on therapy, with monitoring of B cell numbers until B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may require exogenously supplied antibodies or prophylactic antiviral agents to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.
So whilst we are on the subject of COVID…sorry Steve:-(…..another T and B cell paper….but this time abit more info on fingolimod or is it both Fingo and Siponimod…..if so what were the two on the bottom (non converters) taking. You can see that even if you make an antibody response on ocrelizumab. the levels are about 10 times less than other DMT and controls….now if you put J&J/AZ into this mix the levels would be ten times less than Pfizer/Moderna, so a reason to try and avoid if you have the options
Sabatino JJ, Mittl K, Rowles W, Mcpolin K, Rajan JV, Zamecnik CR, Dandekar R, Alvarenga BD, Loudermilk RP, Gerungan C, Spencer CM, Sagan SA, Augusto DG, Alexander J, Hollenbach JA, Wilson MR, Zamvil SS, Bove R. Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity. medRxiv [Preprint]. 2021 Sep 20:2021.09.10.21262933.
Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.
There were only 7 people treated with S1P1 modulator. This is another example where if you test for anti-Spike you are more positive than if you do anti receptor binding domain….Nothing new there really.
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