Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?
COVID-19
SARS-CoV-2 vaccine
anti-CD20
booster dose
fingolimod
multiple sclerosis
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
21
04
2023
received:
10
02
2023
accepted:
28
04
2023
medline:
6
7
2023
pubmed:
8
5
2023
entrez:
8
5
2023
Statut:
ppublish
Résumé
Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4-3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1-2.7, p = 0.012), compared to patients treated with other DMTs. All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff.
Sections du résumé
BACKGROUND AND PURPOSE
Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses.
METHODS
This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.
RESULTS
Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3-100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3-50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2-4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4-3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1-2.7, p = 0.012), compared to patients treated with other DMTs.
CONCLUSIONS
All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff.
Substances chimiques
COVID-19 Vaccines
0
Fingolimod Hydrochloride
G926EC510T
Rituximab
4F4X42SYQ6
Antibodies, Viral
0
Types de publication
Observational Study
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2357-2364Investigateurs
Alessandro Maglione
(A)
Alessia Di Sapio
(A)
Alice Laroni
(A)
Aniello Iovino
(A)
Antonio Mannironi
(A)
Antonio Uccelli
(A)
Barbara Nucciarone
(B)
Carlo Serrati
(C)
Carolina Gabri Nicoletti
(CG)
Caterina Lapucci
(C)
Chiara Rosa Mancinelli
(CR)
Cinzia Cordioli
(C)
Daiana Bezzini
(D)
Daniele Carmagnini
(D)
Davide Brogi
(D)
De Stefano Nicola
(S)
Doriana Landi
(D)
Eduardo Nobile Orazio
(E)
Eleonora Cocco
(E)
Elisabetta Signoriello
(E)
Enri Nako
(E)
Ester Assandri
(E)
Fabiana Marinelli
(F)
Federica Baldi
(F)
Francesca Caleri
(F)
Gabriele Siciliano
(G)
Gaia Cola
(G)
Germana Perego
(G)
Giacomo Lus
(G)
Giampaolo Brichetto
(G)
Gianmarco Bellucci
(G)
Giorgio Da Rin
(G)
Girolama Alessandra Marfia
(GA)
Giulia Vazzoler
(G)
Giuseppe Liberatore
(G)
Giuseppe Trivelli
(G)
Graziella Callari
(G)
Ilaria Gandoglia
(I)
Irene Schiavetti
(I)
Jessica Frau
(J)
Livia Pasquali
(L)
Loredana Petrucci
(L)
Lorena Lorefice
(L)
Lucia Ruggiero
(L)
Marco Salvetti
(M)
Margherita Monti Bragadin
(M)
Maria Chiara Buscarinu
(MC)
Maria Gagliardi
(M)
Maria Pia Sormani
(MP)
Maria Teresa Ferrò
(MT)
Maria Teresa Rilla
(MT)
Marinella Clerico
(M)
Mario Alberto Battaglia
(MA)
Marzia Fronza
(M)
Massimo Del Sette
(M)
Matilde Inglese
(M)
Matteo Scialabba
(M)
Michele Bedognetti
(M)
Monica Ulivelli
(M)
Nicola De Rossi
(N)
Paola Gazzola
(P)
Rachele Bigi
(R)
Raffaele Dubbioso
(R)
Roberta Reniè
(R)
Rosa Iodice
(R)
Sabrina Fabbri
(S)
Sarah Rasia
(S)
Sergio Parodi
(S)
Simona Rolla
(S)
Stefan Platzgummer
(S)
Stromillo Maria Laura
(S)
Tiziana Tassinari
(T)
Valentina Carlini
(V)
Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. 2021;14:175628642110128.
Capuano R, Bisecco A, Conte M, et al. Six-month humoral response to mRNA SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab and fingolimod. Mult Scler Relat Disord. 2022;60:103724.
Sormani MP, Inglese M, Schiavetti I, et al. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies. EBioMedicine. 2021;72:103581.
Schiavetti I, Cordioli C, Stromillo ML, et al. Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies. Mult Scler. 2022;28(13):2106-2111.
Resman RK, Korva M, Knap N, Avšič ŽT, Poljak M. Performance of the rapid high-throughput automated electrochemiluminescence immunoassay targeting total antibodies to the SARS-CoV-2 spike protein receptor binding domain in comparison to the neutralization assay. J Clin Virol. 2021;139:104820.
Sormani MP, Schiavetti I, Inglese M, et al. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy. EBioMedicine. 2022;80:104042.
Achiron A, Dolev M, Menascu S. COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021. Mult Scler J. 2021;27:864-870.
Guerrieri S, Lazzarin S, Nozzolillo A, Filippi M, Moiola L. Serological response to SARS-CoV-2 vaccination in multiple sclerosis patients treated with fingolimod or ocrelizumab: an initial real-life experience. J Neurol. 2021;269(1):39-43.
Inoue T, Shinnakasu R, Kawai C, et al. Antibody feedback contributes to facilitating the development of omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees. J Exp Med. 2023;220(2):e20221786.
Capuano R, Altieri M, Conte M, et al. Humoral response and safety of the third booster dose of BNT162b2 mRNA COVID-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod. J Neurol. 2022;269:6185-6192.
Achiron A, Mandel M, Gurevich M, et al. Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod. J Neurol. 2022;269(5):2286-2292.
Madelon N, Heikkilä N, Sabater Royo I, et al. Omicron-specific cytotoxic T-cell responses after a third dose of mRNA COVID-19 vaccine among patients with multiple sclerosis treated with ocrelizumab. JAMA Neurol. 2022;79(4):399-404.
Brill L, Rechtman A, Zveik O, et al. Humoral and T-cell response to SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab. JAMA Neurol. 2021;78(12):1510-1514.
Canetti M, Barda N, Gilboa M, et al. Immunogenicity and efficacy of fourth BNT162b2 and mRNA1273 COVID-19 vaccine doses; three months follow-up. Nat Commun. 2022;13(1):7711.
Korosec CS, Farhang-Sardroodi S, Dick DW, et al. Long-term durability of immune responses to the BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex. Sci Rep. 2022;12(1):21232.