Immunogenicity and safety of vaccines in multiple sclerosis: A systematic review and meta-analysis

Background: Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis.Methods: MEDLINE(PubMed) and Cochrane databases were searched based on a pre-specified protocol (PROSPERO: CRD42020202018). Studies reporting on patients with MS, diagnosed with McDonald criteria getting vaccinated with any type of vaccine were included in the analysis. The primary endpoint was the incidence of patients being seropositive and experience adverse events after vaccination. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Two reviewers independently screened and reviewed existing literature and assessed study quality with the Methodological index for non-randomized studies.Results: Of 295 articles, 45 studies were analyzed. Seroconversion after COVID-19 vaccines was 76% (95% CI, 70-80; I2 = 95%; 20 studies including 5601 patients. Protection was lower in patients treated with anti-CD20 antibodies and sphingosine-1-phosphate receptor (S1PR) modulators compared to untreated patients or treatment with other DMTs. Relapse occurred in 2% (95% CI, 1-3; I2 = 86%; 16 studies including 7235 patients). Seroconversion after seasonal influenza vaccines was 82% (95% CI, 65-91; I2 = 90%; 6 studies including 490 patients). Relapse rate was similar to this after COVID-19 vaccination.Conclusion: The majority of MS patients vaccinated for COVID-19 or seasonal influenza mount an adequate immune response without safety concerns. Data on other vaccines are limited.