Emma C Tallantyre, Nicola Vickaryous, Valerie Anderson, Aliye Nazli Asardag, David Baker, Jonathan P Bestwick, Kathryn Bramhall, Randy Chance, Nikos Evangelou, Katila George, Gavin Giovannoni, Leanne Grant, Katharine E Harding, Aimee Hibbert, Gillian Ingram, Meleri Jones, Angray S Kang, Samantha Loveless, Stuart Moat, Neil P Robertson,
Abstract
Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.
Competing Interest Statement
ECT has received speaker fees, consultancy fees or travel expenses to attend educational meetings from Merck, Biogen, Roche and Novartis. NV, ANA, RC, MJ, JB, SNS, KG, BD, SL, AH, LG, GI, VA, KB, JS and MU have no conflicts of interest. AK has trademarked GloBody and filed patents for potential commercial development related to the GloBody technology KS has received speaker honoraria from Novartis, Biogen, Teva, Merck KG Aa, Sanofi-Genzyme, and Roche; sat on advisory boards for Novartis, Merck KG Aa, and Roche. He has received grant support from Biogen and Merck. GG has received speaker honoraria from AbbVie, Actelion, Biogen, Celgene, Sanofi-Genzyme, Genentech, Merck-Serono, Novartis, Roche and Teva; sat on advisory boards for AbbVie, Actelion, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche and Teva; and received research support from Sanofi-Genzyme, Takeda, and Merck SJ has received support for conferences, speaker, advisory boards, trials, Data and Safety Monitoring Boards, and projects with CSL Behring, Takeda, Swedish Orphan Biovitrum, Biotest, Binding Site, Grifols, BPL, Octapharma, LFB, Pharming, GSK, Weatherden, Zarodex, Sanofi, and UCB Pharma. None of these conflicts relate to the current work. RD has received speaker honoraria from Biogen Idec, Teva, Merck, Neurology Academy and Sanofi Genzyme; sat on advisory boards for Roche, Merck and Biogen; and received research support from Biogen, Merck and Celgene.
Clinical Trial
N/a
Funding Statement
Support for equipment and consumables used at University Hospital of Wales was provided by Cardiff and Vale UHB and Cardiff University. Kantaro Biosciences, LLC, kindly provided quantitative COVID-19 serologic test kits to measure antibody levels for participants in this study. Salary for Samantha Loveless was partly provided by the BRAIN Unit Infrastructure Award (Grant no: UA05). The BRAIN Unit is funded by Welsh Government through Health and Care Research Wales Work performed at Queen Mary University of London as part of this study at QMUL is funded by Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA with additional support from the MS community via crowdfunding. Assay development was funded by Barts Charity. This work was performed within the PNU, which is funded by Barts Charity.
https://www.medrxiv.org/content/10.1101/2021.07.31.21261326v1
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