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.

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

Clerico, Marinella;Maglione, Alessandro;Rolla, Simona
2021-01-01

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 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.
2021
72
103581
103581
Coronavirus; Immunomodulatory therapies; Multiple sclerosis
Sormani, Maria Pia; Inglese, Matilde; Schiavetti, Irene; Carmisciano, Luca; Laroni, Alice; Lapucci, Caterina; Da Rin, Giorgio; Serrati, Carlo; Gandoglia, Ilaria; Tassinari, Tiziana; Perego, Germana; Brichetto, Giampaolo; Gazzola, Paola; Mannironi, Antonio; Stromillo, Maria Laura; Cordioli, Cinzia; Landi, Doriana; Clerico, Marinella; Signoriello, Elisabetta; Frau, Jessica; Ferrò, Maria Teresa; Di Sapio, Alessia; Pasquali, Livia; Ulivelli, Monica; Marinelli, Fabiana; Callari, Graziella; Iodice, Rosa; Liberatore, Giuseppe; Caleri, Francesca; Repice, Anna Maria; Cordera, Susanna; Battaglia, Mario Alberto; Salvetti, Marco; Franciotta, Diego; Uccelli, Antonio; the, CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS; Maglione, Alessandro; Rolla, Simona
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1888613
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