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Effect of SARS-CoV-2 mRNA Vaccination in MS Patients Treated With Disease Modifying Therapies

21 Pages Posted: 20 Jul 2021

See all articles by Maria Pia Sormani

Maria Pia Sormani

University of Genova - Section of Biostatistics; IRCCS Ospedale Policlinico San Martino

Matilde Inglese

IRCCS Ospedale Policlinico San Martino

Irene Schiavetti

University of Genova - Department of Health Sciences

Luca Carmisciano

University of Genova - Section of Biostatistics

Alice Laroni

University of Genoa - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI)

Caterina Lapucci

IRCCS Ospedale Policlinico San Martino

Giorgio Da Rin

IRCCS Ospedale Policlinico San Martino - Laboratory Medicine

Carlo Serrati

Imperia Hospital - Department of Neurology

Ilaria Gandoglia

Galliera Hospital - Neurology Unit

Tiziana Tassinari

Ospedale Santa Corona Pietra Ligure (Sv) - S.C. Neurologia

Germana Perego

SC Neurologia ASL 4 Chiavarese

Giampaolo Brichetto

AISM Rehabilitation Center

Paola Gazzola

Centro Sclerosi Multipla S.C. Neurologia Asl 3 Genovese

Antonio Mannironi

Sant’Andrea Hospital - Department of Neurology

Maria Laura Stromillo

Università degli Studi di Siena - Clinica Neurologica e Malattie Neurometaboliche

Cinzia Cordioli

Centro Sclerosi Multipla ASST Spedali Civili di Brescia

Doriana Landi

Tor Vergata University and Hospital - Multiple Sclerosis Clinical and Research Unit

Marinella Clerico

Università di Torino - Dipartimento di Scienze Cliniche e Biologiche

Elisabetta Signoriello

Università della Campania Luigi Vanvitelli - Centro Sclerosi Multipla

Jessica Frau

Università di Cagliari - Centro Sclerosi Multipla Ospedale Binaghi Cagliari - ATS Sardegna

Maria Teresa Ferrò

ASST Crema - Neuroimmunology

Alessia Di Sapio

Regina Montis Regalis Hospital - Department of Neurology

Livia Pasquali

University of Pisa - Neurology Unit

Monica Ulivelli

University of Siena - Department of Medicine, Surgery and Neuroscience

Fabiana Marinelli

Fabrizio Spaziani Hospital - Multiple Sclerosis Center

Graziella Callari

UOC Neurologia e Centro SM Fondazione Istituto G. Giglio

Rosa Iodice

Università Federico II di Napopi - Clinica Neurologica

Giuseppe Liberatore

IRCCS Humanitas Research Hospital - Neuromuscular and Neuroimmunology Service

Francesca Caleri

F. Tappeiner Hospital Meran (BZ) - MS Center

Anna Maria Repice

Careggi University Hospital - Department of Neurology 2

Susanna Cordera

Ospedale Regionale - Department of Neurology

Mario Alberto Battaglia

University of Siena - Department of Life Sciences

Marco Salvetti

Sapienza University of Rome - Department of Neuroscience, Mental Health and Sensory Organs, Center for Experimental Neurological Therapies (CENTERS)

Diego Franciotta

IRCCS Ospedale Policlinico San Martino - Autoimmunology Laboratory

Antonio Uccelli

Università degli Studi di Genova - Center of Excellence for Biomedical Research (CEBR)

CovaXiMS Study Group

Independent

More...

Abstract

Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. 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 for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics).

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 multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p<0·001), fingolimod (26-fold decrease, p<0·001) and rituximab (17-fold decrease, p<0·001) were significantly reduced as compared to untreated patients. mRNA-1273 vaccine resulted in a systematically 3·5-fold higher antibody level than the BNT162b2 vaccine (p<0·001).

Interpretation: In pwMS, therapy with anti-CD20 and fingolimod led to a reduced humoral response to SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·5-higher antibody titers than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 or fingolimod. Since it is still unknown the role of T-cells vaccine response, further information is required about the role of cellular immunity triggered by vaccination to better define the most appropriate strategy to vaccinate pwMS under specific DMTs.

Funding Information: FISM [2021/Special-Multi/001]; the Italian Ministry of Health grant ‘Progetto Z844A 5x1000’.

Declaration of Interests: MPS reports grants from Roche, during the conduct of the study; personal fees from Biogen, Merck, Roche, Sanofi, personal fees from Novartis, Medday, Geneuro, Celgene, Mylan, outside the submitted work; MI reports consulting fees from Roche, Merck-Serono, Novartis, Sanofi-Genzyme, Biogen; AL has received personal compensation from Novartis, Sanofi Genzyme, Biogen, Merck, and Roche for public speaking and advisory boards. AL received funding for research by Fondazione Italiana Sclerosi Multipla, the Italian Ministry of Health, and the Italian Ministry of University; CC reports personal fees from Novartis, personal fees from Biogen Idec, personal fees from Almirall, personal fees from Merck Serono, outside the submitted work; DL reports consulting fees Roche, Biogen, Teva, Mylan, Sanofi-Genzyme, fess for advisory boards from Bristol-Celgene, Merck, Novartis, JF reports consulting fees fromSanofi, Biogen, Admirall; ADS reports personal consulting fees from Biogen, Novartis, Genzyme; MS reports research support and personal consulting fees from Merk, Sanofi, Novartis, Biogen, Roche; AU has received personal compensation from Novartis, Biogen, Merck, Roche and Sanofi Genzyme for public speaking and advisory boards. AU received funding for research by Fondazione Italiana Sclerosi Multipla, the Italian Ministry of Health and the European Community. IS, LC, CL, GDR, CS, IG, TT, GP, PG, GPB, AM, MLS, MC, ES, MTF, LP, MU, FM, GC, RI, GL, AMR, FC, SC, MAB, DF, have nothing to dislcose.

Ethics Approval Statement: The study is done in compliance with the principles of the Declaration of Helsinki. The protocol is approved by the regional (CER Liguria: 5/2021 - DB id 11169- 21/01/2021) and the centralized national ethical committee AIFA/Spallanzani (Parere n 351, 2020/21). Written informed consent was obtained from all participants before starting any study procedures.

Keywords: multiple Sclerosis, Coronavirus, Immunomodulatory therapies

Suggested Citation

Sormani, Maria Pia and Inglese, Matilde and Schiavetti, Irene and Carmisciano, Luca and Laroni, Alice and Lapucci, Caterina and Da Rin, Giorgio and Serrati, Carlo and Gandoglia, Ilaria and Tassinari, Tiziana and Perego, Germana and Brichetto, Giampaolo and Gazzola, Paola and Mannironi, Antonio and Stromillo, Maria Laura and Cordioli, Cinzia and Landi, Doriana and Clerico, Marinella and Signoriello, Elisabetta and Frau, Jessica and Ferrò, Maria Teresa and Di Sapio, Alessia and Pasquali, Livia and Ulivelli, Monica and Marinelli, Fabiana and Callari, Graziella and Iodice, Rosa and Liberatore, Giuseppe and Caleri, Francesca and Repice, Anna Maria and Cordera, Susanna and Battaglia, Mario Alberto and Salvetti, Marco and Franciotta, Diego and Uccelli, Antonio and Group, CovaXiMS Study, Effect of SARS-CoV-2 mRNA Vaccination in MS Patients Treated With Disease Modifying Therapies. Available at SSRN: https://ssrn.com/abstract=3886420 or http://dx.doi.org/10.2139/ssrn.3886420

Maria Pia Sormani (Contact Author)

University of Genova - Section of Biostatistics ( email )

Via Pastore 1
Genova, 16132
Italy
+39-3669937472 (Phone)

IRCCS Ospedale Policlinico San Martino

Genoa
Italy

Matilde Inglese

IRCCS Ospedale Policlinico San Martino ( email )

Genoa
Italy

Irene Schiavetti

University of Genova - Department of Health Sciences ( email )

Genova
Italy

Luca Carmisciano

University of Genova - Section of Biostatistics ( email )

Genova
Italy

Alice Laroni

University of Genoa - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI)

Via Vivaldi 5
Genova, 16126
Italy

Caterina Lapucci

IRCCS Ospedale Policlinico San Martino ( email )

Genoa
Italy

Giorgio Da Rin

IRCCS Ospedale Policlinico San Martino - Laboratory Medicine ( email )

Genoa
Italy

Carlo Serrati

Imperia Hospital - Department of Neurology ( email )

Ilaria Gandoglia

Galliera Hospital - Neurology Unit

Genova, 16128
Italy

Tiziana Tassinari

Ospedale Santa Corona Pietra Ligure (Sv) - S.C. Neurologia ( email )

Germana Perego

SC Neurologia ASL 4 Chiavarese ( email )

Giampaolo Brichetto

AISM Rehabilitation Center ( email )

Paola Gazzola

Centro Sclerosi Multipla S.C. Neurologia Asl 3 Genovese ( email )

Antonio Mannironi

Sant’Andrea Hospital - Department of Neurology ( email )

Italy

Maria Laura Stromillo

Università degli Studi di Siena - Clinica Neurologica e Malattie Neurometaboliche ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Cinzia Cordioli

Centro Sclerosi Multipla ASST Spedali Civili di Brescia ( email )

Doriana Landi

Tor Vergata University and Hospital - Multiple Sclerosis Clinical and Research Unit

Via di Tor Vergata
Rome, Lazio 00133
Italy

Marinella Clerico

Università di Torino - Dipartimento di Scienze Cliniche e Biologiche ( email )

Italy

Elisabetta Signoriello

Università della Campania Luigi Vanvitelli - Centro Sclerosi Multipla

Italy

Jessica Frau

Università di Cagliari - Centro Sclerosi Multipla Ospedale Binaghi Cagliari - ATS Sardegna ( email )

Cagliari, 09124
Italy

Maria Teresa Ferrò

ASST Crema - Neuroimmunology ( email )

Alessia Di Sapio

Regina Montis Regalis Hospital - Department of Neurology ( email )

Livia Pasquali

University of Pisa - Neurology Unit ( email )

Lungarno Pacinotti, 43
Pisa PI, 56126
Italy

Monica Ulivelli

University of Siena - Department of Medicine, Surgery and Neuroscience ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Fabiana Marinelli

Fabrizio Spaziani Hospital - Multiple Sclerosis Center ( email )

Graziella Callari

UOC Neurologia e Centro SM Fondazione Istituto G. Giglio ( email )

Rosa Iodice

Università Federico II di Napopi - Clinica Neurologica ( email )

via Cinthia, 4
Naples, Caserta 80126
Italy

Giuseppe Liberatore

IRCCS Humanitas Research Hospital - Neuromuscular and Neuroimmunology Service ( email )

Francesca Caleri

F. Tappeiner Hospital Meran (BZ) - MS Center ( email )

Anna Maria Repice

Careggi University Hospital - Department of Neurology 2 ( email )

Largo Brambilla 3
Florence, 50141
Italy

Susanna Cordera

Ospedale Regionale - Department of Neurology ( email )

Mario Alberto Battaglia

University of Siena - Department of Life Sciences ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Marco Salvetti

Sapienza University of Rome - Department of Neuroscience, Mental Health and Sensory Organs, Center for Experimental Neurological Therapies (CENTERS) ( email )

Rome
Italy

Diego Franciotta

IRCCS Ospedale Policlinico San Martino - Autoimmunology Laboratory ( email )

Genoa
Italy

Antonio Uccelli

Università degli Studi di Genova - Center of Excellence for Biomedical Research (CEBR) ( email )

Genoa
Italy

CovaXiMS Study Group

Independent ( email )

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