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.

Sormani, M.p., Inglese, M., Schiavetti, I., Carmisciano, L., Laroni, A., Lapucci, C., et al. (2021). Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies. EBIOMEDICINE, 72, 103581 [10.1016/j.ebiom.2021.103581].

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

Landi, Doriana;
2021

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26
English
Con Impact Factor ISI
Coronavirus
Immunomodulatory therapies
Multiple sclerosis
2019-nCoV Vaccine mRNA-1273
Adult
Antibodies, Monoclonal, Humanized
Antibody Formation
BNT162 Vaccine
COVID-19
COVID-19 Vaccines
Cladribine
Female
Fingolimod Hydrochloride
Humans
Immunosuppressive Agents
Italy
Male
Middle Aged
Multiple Sclerosis
Prospective Studies
Rituximab
Treatment Outcome
Sormani, M.p., Inglese, M., Schiavetti, I., Carmisciano, L., Laroni, A., Lapucci, C., et al. (2021). Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies. EBIOMEDICINE, 72, 103581 [10.1016/j.ebiom.2021.103581].
Sormani, Mp; Inglese, M; Schiavetti, I; Carmisciano, L; Laroni, A; Lapucci, C; Da Rin, G; Serrati, C; Gandoglia, I; Tassinari, T; Perego, G; Brichetto, G; Gazzola, P; Mannironi, A; Stromillo, Ml; Cordioli, C; Landi, D; Clerico, M; Signoriello, E; Frau, J; Ferrò, Mt; Di Sapio, A; Pasquali, L; Ulivelli, M; Marinelli, F; Callari, G; Iodice, R; Liberatore, G; Caleri, F; Repice, Am; Cordera, S; Battaglia, Ma; Salvetti, M; Franciotta, D; Uccelli, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/306376
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