Response of COVID-19 vaccination in multiple sclerosis patients following disease-modifying therapies: A meta-analysis

Wu, Xi; Wang, Lu; Shen, Lu; Tang, Kefu

doi:10.1016/j.ebiom.2022.104102

Cited by 41 publications

(62 citation statements)

References 59 publications

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“…This led to treatment delays, cessation and switching of agents to avoid lymphopenia and to allow more rapid drug wash-outs in case of infection ( Baker et al, 2020a ). With time, SARS-CoV-2 vaccines and anti-viral agents have been developed to fight the disease that has killed millions of people and created economic havoc ( Khoury et al, 2021 , Wu et al, 2022 , Gombolay et al, 2022 , Sendi et al, 2022 , Richards et al, 2022 ). However, this has created further challenges for use in immunosuppressed people ( Baker et al, 2020a ), especially as this is occurring within a landscape of global viral evolution and the generation of circulating SARS-CoV-2 variants that have different morbidities, contagion and immune-escape ( Chen et al, 2022 , Shrestha et al, 2022 ).…”

Section: Multiple Sclerosis and Disease Modifying Treatmentsmentioning

confidence: 99%

“…However, a modestly worse course of infection seemed to occur in some individuals who were continuously B cell depleted with either ocrelizumab or rituximab, CD20-depleting agents ( Sormani et al, 2021 , Simpson-Yap et al, 2021 , Simpson-Yap et al, 2022 , Reder et al, 2021 ). Furthermore, CD20-depletion was predicted to ( Baker et al, 2020 ) and subsequently shown to limit seroconversion to infection and SARS-CoV-2 vaccines, without major impact on T cell responses, until therapeutic-antibody disappears and B cell repopulation is allowed to occur ( Wu et al, 2022 , Gombolay et al, 2022 , Madelon et al, 2021 , Baker et al, 2021 , Sormani et al, 2021b , Pitzalis et al, 2021 , Tallantyre et al, 2022a , Tallantyre et al, 2022b ). CD20-depletion prevents the generation of immature/naïve B cells capable of producing novel antibody-responses that may have included the inability to form protective, cross-reactive antibodies following natural infection with other (corona)viruses, which could prevent/protect against subsequent SARS-COV-2 infection ( Baker et al, 2020 , Fraley et al, 2021 , Klompus et al, 2021 ).…”

Section: Coronavirus-19 Disease and Issues With Sars-cov-2 Vaccinationmentioning

confidence: 99%

“…Similarly, modest reductions in antibody titres notably with other vaccines, have been seen in fingolimod-treated individuals ( Boulton et al, 2012 , Kappos et al, 2015 , Zoehner et al, 2019 ). However, fingolimod consistently inhibits both seroconversion and peripheral blood T cell responses following SARS-CoV-2 vaccination, although there was some variability between studies in part due to the: individuals, viral strain, past infection, vaccine type; time of assay relative to infection/vaccination, different assays and different functional and physical targets ( Wu et al, 2022 , Gombolay et al, 2022 , Tallantyre et al, 2022a , Tallantyre et al, 2022b , Achiron et al, 2021 , Meyer-Arndt et al, 2022 ). Importantly, this had biological impact because in comparison to other MS treatments, use of either fingolimod or CD20-depleting antibodies was sometimes associated with COVID-19 disease breakthrough following vaccination ( Schiavetti et al, 2022 , Garjani et al, 2022 , Bsteh et al, 2022 , Sormani et al, 2022 ).…”

Section: Coronavirus-19 Disease and Issues With Sars-cov-2 Vaccinationmentioning

confidence: 99%

“…However, S1P1R is involved in the release of immature B cells from bone marrow and B cell migration within lymphoid tissues that involves shuttling of B cells from marginal zones and B cell follicles using S1PR1 and CXCR5, responding to CXCL13 ( Lu and Cyster, 2019 , Cinamon et al, 2008 , Allende et al, 2010 ). This could contribute to the reduction of SARS-CoV-2 B cell responses as seen with fingolimod ( Wu et al, 2022 , Gombolay et al, 2022 ).

Figure 2 Sphinogsine-1-phosphate receptor distribution in human and mouse cells.…”

Section: Sphingosine-one-phosphate Receptor Modulators Used In Multip...mentioning

confidence: 99%

“…Vaccine responses during fingolimod treatment are blunted compared to untreated individuals with a seroconversion rate of 60.2% in a meta-analysis of n=785 people treated with S1PR modulators, largely taking fingolimod n=764 ( Wu et al, 2022 ). This was supported in an additional meta-analysis examining only fingolimod treatment, which reported an antibody response in n=160/220 (72.7%) vaccinated and n=152/198 (76.8%) mRNA-vaccinated, fingolimod-treated individuals ( Table 3 ) ( Gombolay et al, 2022 ).…”

Section: Sphingosine-one-phosphate Receptor Modulators Used In Multip...mentioning

confidence: 99%

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The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

Baker

Forte

Pryce

et al. 2023

Multiple Sclerosis and Related Disorders

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Section: Multiple Sclerosis and Disease Modifying Treatmentsmentioning

confidence: 99%

Section: Coronavirus-19 Disease and Issues With Sars-cov-2 Vaccinationmentioning

confidence: 99%

Section: Coronavirus-19 Disease and Issues With Sars-cov-2 Vaccinationmentioning

confidence: 99%

Figure 2 Sphinogsine-1-phosphate receptor distribution in human and mouse cells.…”

Section: Sphingosine-one-phosphate Receptor Modulators Used In Multip...mentioning

confidence: 99%

Section: Sphingosine-one-phosphate Receptor Modulators Used In Multip...mentioning

confidence: 99%

See 3 more Smart Citations

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

Baker

Forte

Pryce

et al. 2023

Multiple Sclerosis and Related Disorders

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Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis

Smith¹,

Gonzales²,

Li³

et al. 2022

JAMA Netw Open

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ImportanceRituximab and other B-cell–depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear.ObjectivesTo examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2–vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk.Design, Setting, and ParticipantsThis retrospective cohort study used Kaiser Permanente Southern California’s electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2.ExposuresRituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion.Main Outcomes and MeasuresThe main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record.ResultsAmong 3974 SARS-CoV-2–vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49).Conclusions and RelevanceThis cohort study’s findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.

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SARS‐CoV‐2 vaccination and infection in ozanimod‐treated participants with relapsing multiple sclerosis

Cree

Maddux

Bar‐Or

et al. 2023

Ann Clin Transl Neurol

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ObjectiveTo investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination and infection in ozanimod‐treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK.MethodsDAYBREAK (ClinicalTrials.gov‐NCT02576717), an open‐label extension study of oral ozanimod 0.92 mg, enrolled participants aged 18–55 years with RMS who completed phase 1–3 ozanimod trials. Participants who were fully vaccinated against SARS‐CoV‐2 with mRNA or non‐mRNA vaccines, were unvaccinated, and/or had COVID‐19–related adverse events (AEs, with or without vaccination) and postvaccination serum samples were included (n = 288). Spike receptor binding domain (RBD) antibody levels (seroconversion: ≥0.8 U/mL) and serologic evidence of SARS‐CoV‐2 infection (nucleocapsid IgG: ≥1 U/mL) were assessed (Roche Elecsys/Cobas e411 platform).ResultsIn fully vaccinated participants (n = 148), spike RBD antibody seroconversion occurred in 90% (n = 98/109) of those without serologic evidence of prior SARS‐CoV‐2 exposure (100% [n = 80/80] seroconversion after mRNA vaccination) and in 100% (n = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID‐19–related AEs were reported in 10% (n = 15/148) of fully vaccinated participants—all were nonserious and not severe; all participants recovered.InterpretationMost ozanimod‐treated participants with RMS mounted a serologic response to SARS‐CoV‐2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID‐19–related AEs post–full vaccination in participants taking ozanimod were nonserious and not severe.

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Response of COVID-19 vaccination in multiple sclerosis patients following disease-modifying therapies: A meta-analysis

Cited by 41 publications

References 59 publications

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis

SARS‐CoV‐2 vaccination and infection in ozanimod‐treated participants with relapsing multiple sclerosis

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