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

EBioMedicine. 2021 Oct;72:103581. doi: 10.1016/j.ebiom.2021.103581. Epub 2021 Sep 22.


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.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibody Formation / drug effects*
  • BNT162 Vaccine
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / therapeutic use*
  • Cladribine / adverse effects
  • Cladribine / therapeutic use
  • Female
  • Fingolimod Hydrochloride / adverse effects
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Italy
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Prospective Studies
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • COVID-19 Vaccines
  • Immunosuppressive Agents
  • Cladribine
  • Rituximab
  • ocrelizumab
  • 2019-nCoV Vaccine mRNA-1273
  • Fingolimod Hydrochloride
  • BNT162 Vaccine