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

Sormani, M. P.; Schiavetti, I.; Carmisciano, L.; Inglese, M.; Laroni, A.; Lapucci, C.; Uccelli, A.; Da Rin, G.; Serrati, C.; Gandoglia, I.; Tassinari, T.; Perego, G.; Brichetto, G.; Gazzola, P.; Mannironi, A.; Stromillo, M. L.; Cordioli, C.; Landi, D.; Clerico, M.; Signoriello, E.; Frau, J.; Ferro, M. T.; Di Sapio, A.; Pasquali, L.; Ulivelli, M.; Marinelli, F.; Callari, G.; Iodice, R.; Liberatore, G.; Caleri, F.; Repice, A. M.; Cordera, S.; Battaglia, M. A.; Battaglia, M. A.; Salvetti, M.; Franciotta, D.; Maglione, A.; Di Sapio, A.; Signori, A.; Laron, A.; Iovino, A.; Repice, A. M.; Mannironi, A.; Serrati, C.; Nicoletti, C. G.; Mancinelli, C. R.; Cordioli, C.; Bezzini, D.; Carmagnini, D.; Brogi, D.; Qranciotta, D.; Landi, D.; Orazio, E. N.; Cocco, E.; Signoriello, E.; Nako, E.; Assandri, E.; Marinelli, F.; Baldi, F.; Ansaldi, F.; Bovis, F.; Caleri, F.; Siciliano, G.; Cola, G.; Lus, G.; Icardi, G.; Bellucci, G.; Rin, G. D.; Marfia, G. A.; Vazzoler, G.; Trivelli, G.; Callari, G.; Maietta, I.; Frau, J.; Sticchi, L.; Pasquali, L.; Lorefice, L.; Ruggiero, L.; Manzino, M.; Bragadin, M. M.; Buscarinu, M. C.; Gagliardi, M.; Stromillo, M. L.; Ferro, M. T.; Rilla, M. T.; Clerico, M.; Battaglia, M. A.; Ponzano, M.; Fronza, M.; Sette, M. D.; Scialabba, M.; Bedognetti, M.; Ulivelli, M.; De Rossi, N.; De Stefano, N.; Bigi, R.; Dubbioso, R.; Renie, R.; Iodice, R.; Fabbri, S.; Rasia, S.; Rolla, S.; Platzgummer, S.; Cordera, S.; Carlini, V.

doi:10.1016/j.ebiom.2021.103581

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′.

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies / Sormani, M. P.; Schiavetti, I.; Carmisciano, L.; Inglese, M.; Laroni, A.; Lapucci, C.; Uccelli, A.; Da Rin, G.; Serrati, C.; Gandoglia, I.; Tassinari, T.; Perego, G.; Brichetto, G.; Gazzola, P.; Mannironi, A.; Stromillo, M. L.; Cordioli, C.; Landi, D.; Clerico, M.; Signoriello, E.; Frau, J.; Ferro, M. T.; Di Sapio, A.; Pasquali, L.; Ulivelli, M.; Marinelli, F.; Callari, G.; Iodice, R.; Liberatore, G.; Caleri, F.; Repice, A. M.; Cordera, S.; Battaglia, M. A.; Battaglia, M. A.; Salvetti, M.; Franciotta, D.; Maglione, A.; Di Sapio, A.; Signori, A.; Laron, A.; Iovino, A.; Repice, A. M.; Mannironi, A.; Serrati, C.; Nicoletti, C. G.; Mancinelli, C. R.; Cordioli, C.; Bezzini, D.; Carmagnini, D.; Brogi, D.; Qranciotta, D.; Landi, D.; Orazio, E. N.; Cocco, E.; Signoriello, E.; Nako, E.; Assandri, E.; Marinelli, F.; Baldi, F.; Ansaldi, F.; Bovis, F.; Caleri, F.; Siciliano, G.; Cola, G.; Lus, G.; Icardi, G.; Bellucci, G.; Rin, G. D.; Marfia, G. A.; Vazzoler, G.; Trivelli, G.; Callari, G.; Maietta, I.; Frau, J.; Sticchi, L.; Pasquali, L.; Lorefice, L.; Ruggiero, L.; Manzino, M.; Bragadin, M. M.; Buscarinu, M. C.; Gagliardi, M.; Stromillo, M. L.; Ferro, M. T.; Rilla, M. T.; Clerico, M.; Battaglia, M. A.; Ponzano, M.; Fronza, M.; Sette, M. D.; Scialabba, M.; Bedognetti, M.; Ulivelli, M.; De Rossi, N.; De Stefano, N.; Bigi, R.; Dubbioso, R.; Renie, R.; Iodice, R.; Fabbri, S.; Rasia, S.; Rolla, S.; Platzgummer, S.; Cordera, S.; Carlini, V.. - In: EBIOMEDICINE. - ISSN 2352-3964. - 72:(2021), p. 103581. [10.1016/j.ebiom.2021.103581]