1. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies
- Author
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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., Salvetti M., Franciotta D., Maglione A., Signori A., Iovino A., Nicoletti C. G., Mancinelli C. R., Bezzini D., Carmagnini D., Brogi D., Orazio E. N., Cocco E., Nako E., Assandri E., Baldi F., Ansaldi F., Bovis F., Siciliano G., Cola G., Lus G., Icardi G., bellucci G., Rin G. D., Marfia G. A., Vazzoler G., Trivelli G., Maietta I., Sticchi L., Lorefice L., Ruggiero L., Manzino M., Bragadin M. M., Buscarinu M. C., Gagliardi M., Rilla M. T., Ponzano M., Fronza M., Sette M. D., Scialabba M., Bedognetti M., De Rossi N., De Stefano N., Bigi R., Dubbioso R., Renie R., Fabbri S., Rasia S., Rolla S., Platzgummer S., Carlini V., 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., Salvetti, M., Franciotta, D., Maglione, A., Signori, A., Iovino, A., Nicoletti, C. G., Mancinelli, C. R., Bezzini, D., Carmagnini, D., Brogi, D., Orazio, E. N., Cocco, E., Nako, E., Assandri, E., Baldi, F., Ansaldi, F., Bovis, F., Siciliano, G., Cola, G., Lus, G., Icardi, G., Bellucci, G., Rin, G. D., Marfia, G. A., Vazzoler, G., Trivelli, G., Maietta, I., Sticchi, L., Lorefice, L., Ruggiero, L., Manzino, M., Bragadin, M. M., Buscarinu, M. C., Gagliardi, M., Rilla, M. T., Ponzano, M., Fronza, M., Sette, M. D., Scialabba, M., Bedognetti, M., De Rossi, N., De Stefano, N., Bigi, R., Dubbioso, R., Renie, R., Fabbri, S., Rasia, S., Rolla, S., Platzgummer, S., and Carlini, V.
- Subjects
Oncology ,Male ,Medicine (General) ,COVID-19 Vaccine ,Immunosuppressive Agent ,Multiple Sclerosi ,Monoclonal ,Prospective Studies ,Humanized ,biology ,Coronavirus ,Immunomodulatory therapies ,Multiple sclerosis ,General Medicine ,Middle Aged ,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 ,Multiple Sclerosis ,Rituximab ,Treatment Outcome ,Fingolimod ,Vaccination ,Immunomodulatory therapie ,Medicine ,Antibody ,medicine.drug ,Human ,medicine.medical_specialty ,Coronaviru ,Context (language use) ,Settore MED/26 ,Article ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,R5-920 ,Antigen ,Internal medicine ,medicine ,business.industry ,medicine.disease ,Prospective Studie ,biology.protein ,Ocrelizumab ,business - 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′.
- Published
- 2021