Comparison of SARS-CoV-2 antibody response after two doses of mRNA and inactivated vaccines in multiple sclerosis patients treated with disease-modifying therapies

Özakbaş, Serkan; Baba, Cavid; Doğan, Yavuz; Çevik, Sumeyye; Ozcelik, Sinem; Kaya, Ergi

doi:10.1016/j.msard.2022.103486

Cited by 20 publications

(42 citation statements)

References 16 publications

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“…High-certainty evidence confirms significantly lower odds of post-vaccination seroconversion in pwMS on S1PRM compared with UX people (OR [95%CI]: 0.04 [0.03, 0.06], P<0.00001) (Supplementary Figure 5). All included studies 16,17,19-22,25-31 found significantly lower concentrations of antibodies following vaccination in these pwMS compared to UX people. Studies with heterogenous effect measures (moderate-certainty evidence) indicate that with the current vaccination strategy, pwMS on S1PRM are 25 times (95%CI: 16.66, 33.33) less likely to show anti-S1, and 8.33 times (95%CI: 3.70, 20) less likely to show anti-S seroconversion following COVID-19 vaccination (Chi 2 =7.24, P<0.01).…”

Section: Resultsmentioning

confidence: 93%

“…Moderate-certainty evidence did not suggest decreased odds of post-vaccination seroconversion in the pwMS on GA compared to the UX people (OR [95%CI]: 0.87 [0.31, 2.42], P=0.79) (Supplementary Figure 2). Post-vaccination seronegative pwMS on GA were only present in two studies 21,22 – all being among the ones receiving inactivated vaccination. Quantitative analysis in suggested no difference in post-vaccination antibody concentrations between GA-treated pwMS and the UX people in any study.…”

Section: Resultsmentioning

confidence: 93%

“…Moderate-certainty evidence did not suggest any decrease in odds of post-vaccination seroconversion among pwMS on DMF compared to UX people (OR [95%CI]: 1.98 [0.96, 4.09], P=0.07) (Supplementary Figure 3). Seven studies 16,18,19,22,23,25,26 did not contain any seronegative pwMS on DMF following mRNA or inactivated vaccination; Quantitative analysis suggested no difference in post-vaccination antibody concentrations compared to UX people.…”

Section: Resultsmentioning

confidence: 96%

“…No evidence was found regarding anti-S seroconversion. In five studies 16,19,20,22,25 , all CLAD-treated pwMS seroconverted following vaccination similar to the UX people, preventing relative effect measurement. Quantitative analysis in no studies suggested lower concentrations of post-vaccination antibodies among them.…”

Section: Resultsmentioning

confidence: 99%

“…Paradoxical to the healthy population, low-certainty evidence – due to limited count of inactivated vaccine studies – suggests that among the pwMS on S1PRM, odds of anti-S1 seroconversion is higher with inactivated vaccines compared to mRNA and AV vaccines (Chi 2 =11.97, P<0.001). Although theoretically reasonable 32 , head-to-head mRNA-AV 29 and mRNA-inactivated 22 immunogenicity comparisons in S1PRM-treated pwMS have suggested the opposite. Hence, the need for more replication of inactivated/mRNA/AV comparisons is clearly sensed for pwMS on S1PRM.…”

Section: Resultsmentioning

confidence: 99%

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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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.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis

Müller,

Cagol,

Lorscheider

et al. 2023

JAMA Neurol

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ImportanceEmerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.ObjectiveTo summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.Evidence ReviewA literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022.FindingsOf 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult.Conclusion and RelevancePIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets.

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

Kister

Curtin

Pei³

et al. 2022

Ann Clin Transl Neurol

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Objective: To compare "hybrid immunity" (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses. Methods: Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed primary COVID-19 vaccination series ≥6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFNc and IL-2 assay and, in a subset, with IFNc and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product. Results: Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 (AE7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. Interpretation: Prior COVID-19 infection is associated with enhanced antibody and cellular postvaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

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Comparison of SARS-CoV-2 antibody response after two doses of mRNA and inactivated vaccines in multiple sclerosis patients treated with disease-modifying therapies

Cited by 20 publications

References 16 publications

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

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

Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis

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

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