Importance: An evidence-based appraisal of the COVID-19 vaccination policies among people with multiple sclerosis (pwMS) with respect to disease-modifying therapies (DMT) is important for our understandings and their further management.
Objective: To synthesize the available evidence concerning the effect of DMTs on COVID-19 vaccination immunogenicity and effectiveness.
Data Sources: We searched MEDLINE, Scopus, Web of Science, MedRxiv, and Google Scholar from January 2021 until January 2022.
Study Selection: The exclusion criteria included: not a primary investigation; retracted/withdrawn; no eligible participants - people with no history/evidence of previous COVID-19 and corticosteroid administration within two months of vaccination; no eligible exposures - all nine DMT classes; and no eligible comparators - DMT-unexposed at the time of vaccination.
Data Extraction and Synthesis: Entries were assessed independently by two reviewers for eligibility and quality. Dichotomized data was extracted by two reviewers in accordance with Cochrane guidelines, and were pooled using either Peto fixed-effects or Inverse-variance random-effects methods.
Main Outcomes and Measures: Main outcomes were i) B-cell response, measured by seroconversion odds ratio (OR); ii) T-cell response, measured by interferon-gamma release response OR, and CD4+/CD8+ activation-induced marker+ OR. Further outcomes including immunity waning speed and breakthrough COVID-19 incidence/severity were synthesized narratively.
Results: Data from 28 studies (5,025 pwMS and 1,635 healthy participants) after COVID-19 vaccination suggests mildly-lower B-cell responses in teriflunomide- and alemtuzumab-treated, extensively-lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM)- and anti-CD20 (aCD20)-treated, and lower T-cell responses in interferon-, S1PRM-, alemtuzumab- and cladribine-treated pwMS. Every ten-week increase in aCD20-to-vaccine period is associated with a 1.94-time (95%CI: 1.57, 2.41, P<0.00001) increase in odds of seroconversion. B-cell-depleting therapies seem to accelerate post-vaccination humoral waning, and booster immunogenicity is predictable with the same factors affecting the priming vaccination. Furthermore, comparatively-increased breakthrough COVID-19 incidence and severity is being observed only among S1PRM- and anti-CD20-treated pwMS - i.e., among the pwMS with extensively-blunted B-cell response, despite adequate T-cell responses in the aCD20-treated. To date, pwMS on only-T-cell-blunting DMTs have not shown increased susceptibility to breakthrough COVID-19.
Conclusion and Relevance: The implemented vaccination strategy to date has been effective for pwMS on all DMTs other than S1PRM and aCD20. As B-cell immunity seems to be a more important predictor of vaccine effectiveness than T-cell immunity, optimization of humoral immunogenicity and ensuring its durability among pwMS on DMTs are the necessities of an effective COVID-19 vaccination policy.