tetano
Editor, Senior Moderator
EBioMedicine
. 2021 Sep 19;103581.
doi: 10.1016/j.ebiom.2021.103581. Online ahead of print.
Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies
Maria Pia Sormani[SUP] 1 [/SUP], Matilde Inglese[SUP] 2 [/SUP], Irene Schiavetti[SUP] 3 [/SUP], Luca Carmisciano[SUP] 3 [/SUP], Alice Laroni[SUP] 2 [/SUP], Caterina Lapucci[SUP] 2 [/SUP], Giorgio Da Rin[SUP] 4 [/SUP], Carlo Serrati[SUP] 5 [/SUP], Ilaria Gandoglia[SUP] 6 [/SUP], Tiziana Tassinari[SUP] 7 [/SUP], Germana Perego[SUP] 8 [/SUP], Giampaolo Brichetto[SUP] 9 [/SUP], Paola Gazzola[SUP] 10 [/SUP], Antonio Mannironi[SUP] 11 [/SUP], Maria Laura Stromillo[SUP] 12 [/SUP], Cinzia Cordioli[SUP] 13 [/SUP], Doriana Landi[SUP] 14 [/SUP], Marinella Clerico[SUP] 15 [/SUP], Elisabetta Signoriello[SUP] 16 [/SUP], Jessica Frau[SUP] 17 [/SUP], Maria Teresa Ferrò[SUP] 18 [/SUP], Alessia Di Sapio[SUP] 19 [/SUP], Livia Pasquali[SUP] 20 [/SUP], Monica Ulivelli[SUP] 21 [/SUP], Fabiana Marinelli[SUP] 22 [/SUP], Graziella Callari[SUP] 23 [/SUP], Rosa Iodice[SUP] 24 [/SUP], Giuseppe Liberatore[SUP] 25 [/SUP], Francesca Caleri[SUP] 26 [/SUP], Anna Maria Repice[SUP] 27 [/SUP], Susanna Cordera[SUP] 28 [/SUP], Mario Alberto Battaglia[SUP] 29 [/SUP], Marco Salvetti[SUP] 30 [/SUP], Diego Franciotta[SUP] 31 [/SUP], Antonio Uccelli[SUP] 2 [/SUP], CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
Affiliations
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'.
Keywords: Coronavirus; Immunomodulatory therapies; Multiple sclerosis.
. 2021 Sep 19;103581.
doi: 10.1016/j.ebiom.2021.103581. Online ahead of print.
Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies
Maria Pia Sormani[SUP] 1 [/SUP], Matilde Inglese[SUP] 2 [/SUP], Irene Schiavetti[SUP] 3 [/SUP], Luca Carmisciano[SUP] 3 [/SUP], Alice Laroni[SUP] 2 [/SUP], Caterina Lapucci[SUP] 2 [/SUP], Giorgio Da Rin[SUP] 4 [/SUP], Carlo Serrati[SUP] 5 [/SUP], Ilaria Gandoglia[SUP] 6 [/SUP], Tiziana Tassinari[SUP] 7 [/SUP], Germana Perego[SUP] 8 [/SUP], Giampaolo Brichetto[SUP] 9 [/SUP], Paola Gazzola[SUP] 10 [/SUP], Antonio Mannironi[SUP] 11 [/SUP], Maria Laura Stromillo[SUP] 12 [/SUP], Cinzia Cordioli[SUP] 13 [/SUP], Doriana Landi[SUP] 14 [/SUP], Marinella Clerico[SUP] 15 [/SUP], Elisabetta Signoriello[SUP] 16 [/SUP], Jessica Frau[SUP] 17 [/SUP], Maria Teresa Ferrò[SUP] 18 [/SUP], Alessia Di Sapio[SUP] 19 [/SUP], Livia Pasquali[SUP] 20 [/SUP], Monica Ulivelli[SUP] 21 [/SUP], Fabiana Marinelli[SUP] 22 [/SUP], Graziella Callari[SUP] 23 [/SUP], Rosa Iodice[SUP] 24 [/SUP], Giuseppe Liberatore[SUP] 25 [/SUP], Francesca Caleri[SUP] 26 [/SUP], Anna Maria Repice[SUP] 27 [/SUP], Susanna Cordera[SUP] 28 [/SUP], Mario Alberto Battaglia[SUP] 29 [/SUP], Marco Salvetti[SUP] 30 [/SUP], Diego Franciotta[SUP] 31 [/SUP], Antonio Uccelli[SUP] 2 [/SUP], CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
Affiliations
- PMID: 34563483
- DOI: 10.1016/j.ebiom.2021.103581
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'.
Keywords: Coronavirus; Immunomodulatory therapies; Multiple sclerosis.