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Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis
  1. Masoud Etemadifar1,
  2. Hosein Nouri1,2,
  3. Maristella Pitzalis3,
  4. Maria Laura Idda3,
  5. Mehri Salari4,
  6. Mahshid Baratian5,
  7. Sepide Mahdavi5,
  8. Amir Parsa Abhari1,2,
  9. Nahad Sedaghat1,2
  1. 1 Neurosurgery Research Department, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2 Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Isfahan, Iran
  3. 3 Institute of Genetic and Biomedical Research (IRGB) of the National Research Council (CNR), Cagliari, Italy
  4. 4 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5 Clinical Research Developement Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran
  1. Correspondence to Dr Nahad Sedaghat, Neurosurgery Research Department, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; nahad.sedaghat{at}


Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines’ immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS—although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters’ immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20—unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

  • COVID-19

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  • Contributors ME: supervision, resources. MP, MLI: resources, writing—review and editing. MS: writing—review and editing. APA: writing—initial draft, writing—review and editing. MB, SM: screening entries, quality assessment. HN: quality assessment, certainty assessment. NS: supervision, screening entries, certainty assessment, formal analysis, writing—initial draft, writing—review and editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.