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Observational Study
. 2021 Oct:72:103581.
doi: 10.1016/j.ebiom.2021.103581. Epub 2021 Sep 22.

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

Maria Pia Sormani  1 , Matilde Inglese  2 , Irene Schiavetti  3 , Luca Carmisciano  3 , Alice Laroni  2 , Caterina Lapucci  2 , Giorgio Da Rin  4 , Carlo Serrati  5 , Ilaria Gandoglia  6 , Tiziana Tassinari  7 , Germana Perego  8 , Giampaolo Brichetto  9 , Paola Gazzola  10 , Antonio Mannironi  11 , Maria Laura Stromillo  12 , Cinzia Cordioli  13 , Doriana Landi  14 , Marinella Clerico  15 , Elisabetta Signoriello  16 , Jessica Frau  17 , Maria Teresa Ferrò  18 , Alessia Di Sapio  19 , Livia Pasquali  20 , Monica Ulivelli  21 , Fabiana Marinelli  22 , Graziella Callari  23 , Rosa Iodice  24 , Giuseppe Liberatore  25 , Francesca Caleri  26 , Anna Maria Repice  27 , Susanna Cordera  28 , Mario Alberto Battaglia  29 , Marco Salvetti  30 , Diego Franciotta  31 , Antonio Uccelli  2 ; CovaXiMS study group on behalf of the Italian Covid-19 Alliance in MS
Collaborators, Affiliations
Observational Study

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

Maria Pia Sormani et al. EBioMedicine. 2021 Oct.

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.

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Conflict of interest statement

Declaration of Competing Interest Caleri F received personal compensations from Merck, Biogen, Genzyme, Roche, Teva. Clerico M received grants and consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche, Almirall. Cordioli C received personal compensations from Merck, Biogen, Novartis, Roche, Almirall. Di Sapio A received consulting fees from Novartis, Biogen, Genzyme. Franciotta D received personal honoraria from Merck, Biogen, Sanofi-Genzyme, Roche. Frau J received consulting fees from Biogen, Sanofi-Genzyme, Almirall. Inglese received consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche. Iodice received personal honoraria from Merck, Biogen, Sanofi-Genzyme, Roche. Landi received consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche, Teva, Mylan, Bristol-Celgene. Laroni received consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche. Salvetti received consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche. Serrati received grants from Neopharmed. Sormani received consulting fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Roche, Celgene, Geneuro, GSK, Medday, Immunic. Uccelli participated in advisory boards for Biogen, Roche. Ulivelli received consulting fees from Biogen, Novartis, Serono. Battaglia MA, Brichetto G, Callari G, Carmisciano L, Cordera S, Da Rin G, Ferrò MT, Gandoglia I, Gazzola P Lapucci C, Liberatore G, Mannironi A, Marinelli F, Pasquali L, Perego G, Repice AM, Schiavetti I, Signoriello E, Stromillo ML, Tassinari T, have nothing to disclose.

Figures

Fig. 1
Fig. 1
Post-vaccination RBD antibody levels by disease modifying treatment in relation to vaccine type. Footnote: ga=glatiramer-acetate, ifn=interferon, alem=alemtuzumab, clad=cladribine, dmf=dimethyl-fumarate, teri=teriflunomide, rtx=rituximab, fty=fingolimod, ocre=ocrelizumab.
Fig. 2
Fig. 2
Post-vaccination RBD antibody levels in patients treated with anti-CD20 therapies according to the time passed since the last infusion.
Fig. 3
Fig. 3
Anti-SARS-CoV-2 RBD antibody titers in patients treated with fingolimod according to their lymphocyte counts (measured within one month since the first dose of vaccine).
See this image and copyright information in PMC

Comment in

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