Immunogenicity and safety of mRNA COVID-19 vaccines in people with multiple sclerosis treated with different disease-modifying therapies

Capone, Fioravante; Lucchini, Matteo; Ferraro, Elisabetta; Bianco, Assunta; Rossi, Mariagrazia; Cicia, Alessandra; Cortese, Antonio; Cruciani, Alessandro; Arcangelis, Vania De; Giglio, Laura De; Motolese, Francesco; Sancetta, Biagio; Mirabella, Massimiliano; Lazzaro, Vincenzo Di

doi:10.1007/s13311-021-01165-9

Cited by 38 publications

(57 citation statements)

References 29 publications

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“…Moderate-certainty evidence does not suggest decreased odds of post-vaccination seroconversion in the pwMS on IFNs compared to people unexposed (UX) to DMTs (OR [95%CI]: 0.84 [0.38, 1.83], P=0.66) (Supplementary Figure 1). No seronegative pwMS on IFN were present in four studies 16-19 . Quantitative analysis in studies also did not suggest lower concentrations of antibodies among these pwMS post-vaccination.…”

Section: Resultsmentioning

confidence: 91%

“…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: 92%

“…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: 97%

“…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%

“…Compared to UX people, low-certainty evidence did not confirm lower odds of anti-S1 seroconversion among pwMS on NTZ following vaccination (OR [95%CI]: 0.53 [0.24, 1.18]) (Supplementary Figure 7). All pwMS on NTZ in seven studies – including the only two studies using anti-S assays with extractable data 23,36 – seroconverted following vaccination 16,17,23,25,26,28,36 . Although relative effect was measurable in only two of them which contained seronegative UX people 26,28 .…”

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: 91%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 97%

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

View full text Add to dashboard Cite

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Immune responses to SARS‐CoV‐2 vaccination in multiple sclerosis: a systematic review/meta‐analysis

Gombolay

Dutt

Tyor

2022

Ann Clin Transl Neurol

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Introduction Responses to SARS‐CoV‐2 vaccination in patients with MS (pwMS) varies by disease‐modifying therapies (DMTs). We perform a meta‐analysis and systematic review of immune response to SARS‐CoV‐2 vaccines in pwMS. Methods Two independent reviewers searched PubMed, Google Scholar, and Embase from January 1, 2019‐December 31, 2021, excluding prior SARS‐CoV‐2 infections. The meta‐analysis of observational studies in epidemiology (MOOSE) guidelines were applied. The data were pooled using a fixed‐effects model. Results Eight‐hundred sixty‐four healthy controls and 2203 pwMS from 31 studies were included. Antibodies were detected in 93% healthy controls (HCs), and 77% pwMS, with >93% responses in all DMTs (interferon‐beta, glatiramer acetate, cladribine, natalizumab, dimethyl fumarate, alemtuzumab, and teriflunomide) except for 72% sphingosine‐1‐phosphate modulators (S1PM) and 44% anti‐CD20 monoclonal antibodies (mAbs). T‐cell responses were detected in most anti‐CD20 and decreased in S1PM. Higher antibody response was observed in mRNA vaccines (99.7% HCs) versus non‐mRNA vaccines (HCs: 72% inactivated virus; pwMS: 86% vector, 59% inactivated virus). A multivariate logistic regression model to predict vaccine response demonstrated that mRNA versus non‐mRNA vaccines had a 3.4 odds ratio (OR) for developing immunity in anti‐CD20 (p = 0.0052) and 7.9 OR in pwMS on S1PM or CD20 mAbs (p < 0.0001). Antibody testing timing did not affect antibody detection. Conclusion Antibody responses are decreased in S1PM and anti‐CD20; however, cellular responses were positive in most anti‐CD20 with decreased T cell responses in S1PM. mRNA vaccines had increased seroconversion rates compared to non‐RNA vaccines. Further investigation in how DMTs affect vaccine immunity are needed.

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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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Immunogenicity and safety of mRNA COVID-19 vaccines in people with multiple sclerosis treated with different disease-modifying therapies

Cited by 38 publications

References 29 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

Immune responses to SARS‐CoV‐2 vaccination in multiple sclerosis: a systematic review/meta‐analysis

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

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