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

被引：199

作者：

Sormani, Maria Pia ^{[1
,2
]}

Inglese, Matilde ^{[2
,3
,4
]}

Schiavetti, Irene ^{[1
]}

Carmisciano, Luca ^{[1
]}

Laroni, Alice ^{[2
,3
,4
]}

Lapucci, Caterina ^{[2
,3
,4
]}

Da Rin, Giorgio ^{[5
]}

Serrati, Carlo ^{[6
]}

Gandoglia, Ilaria ^{[7
]}

Tassinari, Tiziana ^{[8
]}

Perego, Germana ^{[9
]}

Brichetto, Giampaolo ^{[10
]}

Gazzola, Paola ^{[11
]}

Mannironi, Antonio ^{[12
]}

Stromillo, Maria Laura ^{[13
]}

Cordioli, Cinzia ^{[14
]}

Landi, Doriana ^{[15
]}

Clerico, Marinella ^{[16
]}

Signoriello, Elisabetta ^{[17
]}

Frau, Jessica ^{[18
]}

Ferro, Maria Teresa ^{[19
]}

Di Sapio, Alessia ^{[20
]}

Pasquali, Livia ^{[21
]}

Ulivelli, Monica ^{[22
]}

Marinelli, Fabiana ^{[23
]}

Callari, Graziella ^{[24
,25
]}

Iodice, Rosa ^{[26
]}

Liberatore, Giuseppe ^{[27
]}

Caleri, Francesca ^{[28
]}

Repice, Anna Maria ^{[29
]}

Cordera, Susanna ^{[30
]}

Battaglia, Mario Alberto ^{[31
,32
]}

Salvetti, Marco ^{[33
,34
]}

Franciotta, Diego ^{[35
]}

Uccelli, Antonio ^{[2
,3
,4
]}

机构：

[1] Univ Genoa, Dept Hlth Sci, Sect Biostat, Genoa, Italy

[2] IRCCS Osped Policlin San Martino, Genoa, Italy

[3] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[4] Univ Genoa, Ctr Excellence Biomed Res CEBR, Genoa, Italy

[5] IRCCS Osped Policlin San Martino, Lab Med, Genoa, Italy

[6] Imperia Hosp, Dept Neurol, Imperia, Italy

[7] Galliera Hosp, Neurol Unit, Genoa, Italy

[8] Osped Santa Corona, SC Neurol, Pietra Ligure, SV, Italy

[9] ASL 4 Chiavarese, SC Neurol, Chiavari, Italy

[10] AISM Rehabil Ctr, Genoa, Italy

[11] Asl 3 Genovese, Ctr Sclerosi Multipla, SC Neurol, Genoa, Italy

[12] St Andrea Hosp, Dept Neurol, La Spezia, Italy

[13] Univ Siena, Clin Neurol & Malattie Neurometab, Siena, Italy

[14] ASST Spedali Civili Brescia, Ctr Sclerosi Multipla, Brescia, Italy

[15] Tor Vergata Univ & Hosp, Dept Syst Med, Multiple Sclerosis Clin & Res Unit, Rome, Italy

[16] Univ Torino, Dipartimento Sci Clin & Biol, Turin, Italy

[17] Univ Campania Luigi Vanvitelli, Ctr Sclerosi Multipla, Clin Neurol 2, Caserta, Italy

[18] Univ Cagliari, Ctr Sclerosi Multipla, ATS Sardegna, Osped Binaghi Cagliari, Cagliari, Italy

[19] ASST Crema, Cerobrovasc Dept, Neurol Unit, Neuroimmunol,Ctr Multiple Sclerosis, Crema, Italy

[20] Regina Montis Regalis Hosp, Dept Neurol, Mondovi, Italy

[21] Univ Pisa, Dept Clin & Expt Med, Neurol Unit, Pisa, Italy

[22] Univ Siena, Dept Med Surg & Neurosci, Siena, Italy

[23] Fabrizio Spaziani Hosp, Multiple Sclerosis Ctr, Via Armando Fabi, Frosinone, Italy

[24] UOC Neurol, Cefalu, Italy

[25] Ctr SM Fdn Ist G Giglio, Cefalu, Italy

[26] DSNRO Univ Federico II Napoli, Clin Neurol, Naples, Italy

[27] IRCCS Humanitas Res Hosp, Neuromuscular & Neuroimmunol Serv, Rozzano, Italy

[28] F Tappeiner Hosp, MS Ctr, Dept Neurol, Meran, BZ, Italy

[29] Careggi Univ Hosp, Dept Neurol 2, Florence, Italy

[30] Osped Reg, Dept Neurol, Aosta, Italy

[31] Italian Multiple Sclerosis Fdn, Res Dept, Genoa, Italy

[32] Univ Siena, Dept Life Sci, Siena, Italy

[33] Sapienza Univ Rome, Ctr Expt Neurol Therapies CENTERS, Dept Neurosci Mental Hlth & Sensory Organs, Rome, Italy

[34] IRCCS Ist Neurol Mediterraneo Neuromed, Pozzilli, Italy

[35] IRCCS Osped Policlin San Martino, Autoimmunol Lab, Genoa, Italy

来源：

EBIOMEDICINE | 2021年 / 72卷

关键词：

Multiple sclerosis; Coronavirus; Immunomodulatory therapies;

D O I：

10.1016/j.ebiom.2021.103581

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 antiCD20 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 x 1000'. (C) 2021 The Authors. Published by Elsevier B.V.

引用

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