Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

the CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS

doi:10.1016/j.ebiom.2021.103581

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

the CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS

Research output: Contribution to journal › Article › peer-review

187 Scopus citations

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′.

Original language	English
Article number	103581
Journal	eBioMedicine
Volume	72
DOIs	https://doi.org/10.1016/j.ebiom.2021.103581
State	Published - Oct 2021
Externally published	Yes

Keywords

Coronavirus
Immunomodulatory therapies
Multiple sclerosis

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10.1016/j.ebiom.2021.103581

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@article{0f723e02d87041fe9c9eb29d035d8da8,

title = "Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies",

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{\textquoteleft}Progetto Z844A 5 × 1000′.",

keywords = "Coronavirus, Immunomodulatory therapies, Multiple sclerosis",

author = "{the CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS} and Sormani, {Maria Pia} and Irene Schiavetti and Luca Carmisciano and Matilde Inglese and Alice Laroni and Caterina Lapucci and Antonio Uccelli and {Da Rin}, Giorgio and Carlo Serrati and Ilaria Gandoglia and Tiziana Tassinari and Germana Perego and Giampaolo Brichetto and Paola Gazzola and Antonio Mannironi and Stromillo, {Maria Laura} and Cinzia Cordioli and Doriana Landi and Marinella Clerico and Elisabetta Signoriello and Jessica Frau and Ferr{\`o}, {Maria Teresa} and {Di Sapio}, Alessia and Livia Pasquali and Monica Ulivelli and Fabiana Marinelli and Graziella Callari and Rosa Iodice and Giuseppe Liberatore and Francesca Caleri and Repice, {Anna Maria} and Susanna Cordera and Battaglia, {Mario Alberto} and Battaglia, {Mario Alberto} and Marco Salvetti and Diego Franciotta and Alessandro Maglione and Alessio Signori and A. Laron and Aniello Iovino and Repice, {Anna Maria} and Antonio Mannironi and Carlo Serrati and Nicoletti, {Carolina Gabri} and Mancinelli, {Chiara Rosa} and Cinzia Cordioli and Daiana Bezzini and Daniele Carmagnini and Davide Brogi and D. Qranciotta",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = oct,

doi = "10.1016/j.ebiom.2021.103581",

language = "English",

volume = "72",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

AU - the CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS

AU - Sormani, Maria Pia

AU - Schiavetti, Irene

AU - Carmisciano, Luca

AU - Inglese, Matilde

AU - Laroni, Alice

AU - Lapucci, Caterina

AU - Uccelli, Antonio

AU - Da Rin, Giorgio

AU - Serrati, Carlo

AU - Gandoglia, Ilaria

AU - Tassinari, Tiziana

AU - Perego, Germana

AU - Brichetto, Giampaolo

AU - Gazzola, Paola

AU - Mannironi, Antonio

AU - Stromillo, Maria Laura

AU - Cordioli, Cinzia

AU - Landi, Doriana

AU - Clerico, Marinella

AU - Signoriello, Elisabetta

AU - Frau, Jessica

AU - Ferrò, Maria Teresa

AU - Di Sapio, Alessia

AU - Pasquali, Livia

AU - Ulivelli, Monica

AU - Marinelli, Fabiana

AU - Callari, Graziella

AU - Iodice, Rosa

AU - Liberatore, Giuseppe

AU - Caleri, Francesca

AU - Repice, Anna Maria

AU - Cordera, Susanna

AU - Battaglia, Mario Alberto

AU - Salvetti, Marco

AU - Franciotta, Diego

AU - Maglione, Alessandro

AU - Signori, Alessio

AU - Laron, A.

AU - Iovino, Aniello

AU - Repice, Anna Maria

AU - Mannironi, Antonio

AU - Serrati, Carlo

AU - Nicoletti, Carolina Gabri

AU - Mancinelli, Chiara Rosa

AU - Cordioli, Cinzia

AU - Bezzini, Daiana

AU - Carmagnini, Daniele

AU - Brogi, Davide

AU - Qranciotta, D.

PY - 2021/10

Y1 - 2021/10

N2 - 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′.

AB - 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′.

KW - Coronavirus

KW - Immunomodulatory therapies

KW - Multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=85121098563&partnerID=8YFLogxK

U2 - 10.1016/j.ebiom.2021.103581

DO - 10.1016/j.ebiom.2021.103581

M3 - Article

C2 - 34563483

AN - SCOPUS:85121098563

SN - 2352-3964

VL - 72

JO - eBioMedicine

JF - eBioMedicine

M1 - 103581

ER -

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies

Abstract

Keywords

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