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EBioMedicine
. 2021 Sep 19;103581.
doi: 10.1016/j.ebiom.2021.103581. Online ahead of print.
Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies
Maria Pia Sormani 1 , Matilde Inglese 2 , Irene Schiavetti 3 , Luca Carmisciano 3 , Alice Laroni 2 , Caterina Lapucci 2 , Giorgio Da Rin 4 , Carlo Serrati 5 , Ilaria Gandoglia 6 , Tiziana Tassinari 7 , Germana Perego 8 , Giampaolo Brichetto 9 , Paola Gazzola 10 , Antonio Mannironi 11 , Maria Laura Stromillo 12 , Cinzia Cordioli 13 , Doriana Landi 14 , Marinella Clerico 15 , Elisabetta Signoriello 16 , Jessica Frau 17 , Maria Teresa Ferrò 18 , Alessia Di Sapio 19 , Livia Pasquali 20 , Monica Ulivelli 21 , Fabiana Marinelli 22 , Graziella Callari 23 , Rosa Iodice 24 , Giuseppe Liberatore 25 , Francesca Caleri 26 , Anna Maria Repice 27 , Susanna Cordera 28 , Mario Alberto Battaglia 29 , Marco Salvetti 30 , Diego Franciotta 31 , Antonio Uccelli 2 , CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
Affiliations
- PMID: 34563483
- DOI: 10.1016/j.ebiom.2021.103581
Abstract
Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response.
Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression.
Findings: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days).
Interpretation: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS.
Funding: FISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.
Keywords: Coronavirus; Immunomodulatory therapies; Multiple sclerosis.