Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Abstract

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.

Hybrid and vaccine‐induced immunity against SAR‐CoV‐2 in MS patients on different disease‐modifying therapies

“…We demonstrated that PI markedly enhances post‐vaccine humoral and, and, to a lesser extent, cellular responses across DMTs, that is, that the immunologic benefits of PI extended to patients on DMT classes—aCD20 and S1P—that are associated with attenuated post‐infection 44 , 53 , 54 and post‐vaccination responses. 24 , 25 Thus, vaccinated MS patients on aCD20 and S1P therapies who had prior COVID‐19 infection—and these currently comprise the majority of patients in the United States—likely have significantly better immune protection than would be expected based on published studies of vaccination‐only immune responses. 24 , 25 , 55 Moreover, our results suggest that it may be possible to improve humoral and cellular immune response defenses following repeated exposure to virus‐specific antigens even in patients whose immune system has been partially compromised by medications.…”

“… 24 , 25 Thus, vaccinated MS patients on aCD20 and S1P therapies who had prior COVID‐19 infection—and these currently comprise the majority of patients in the United States—likely have significantly better immune protection than would be expected based on published studies of vaccination‐only immune responses. 24 , 25 , 55 Moreover, our results suggest that it may be possible to improve humoral and cellular immune response defenses following repeated exposure to virus‐specific antigens even in patients whose immune system has been partially compromised by medications. By its nature, exposure to viral infection is associated with unpredictable, potentially serious short‐ and long‐term adverse events and is inadvisable for anyone, especially the immunocompromised.…”

“… 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 In a meta‐analysis of COVID‐19 vaccine studies in MS, post‐vaccine seroconversion rates were 13‐fold lower among patients on B‐cell depleting anti‐CD20 therapies (aCD20) and eightfold lower with S1P receptor modulators (S1P) as compared to patients not on a DMT. 24 Post‐vaccine T‐cell activation post‐vaccine is suppressed with S1P 18 , 21 , 22 , 25 but largely intact with B‐cell depleting therapies even in the absence of antibody responses. 4 , 6 , 8 , 10 , 16 , 17 , 18 , 21 , 22 , 25 , 26 , 27 …”

Monkeypox in Multiple Sclerosis patients: Should we be alert?

“…Lower effective cellular immune responses through CD4 + and CD8 + T lymphocytes after SARS-CoV-2 vaccination were also suggested for MS patients during interferon, fingolimod and cladribine treatments ( Etemadifar et al., 2022 ; Gombolay et al., 2022 ; Iannetta et al., 2022 ; Tortorella et al., 2022 ).…”

“…Regarding vaccination, MS patients presented different neutralizing antibody responses against SARS-CoV-2 (77%) vs. healthy controls (93%). MS patients during disease-modifying therapies (DMTs) exhibited: >93% positive antibody responses during glatiramer acetate, beta-interferons, dimethyl-fumarate, teriflunomide, alemtuzumab, and natalizumab; while those treated with fingolimod (27%) and anti-CD20 therapies (44%) showed lower positive antibody responses ( Etemadifar et al., 2022 ; Gombolay et al., 2022 ).…”