Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease
ObjectiveTo investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.MethodsEstablished patients at New York University Langone Health with IMID (n=51) receiving the BNT...
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| Published in | Annals of the rheumatic diseases Vol. 80; no. 10; pp. 1339 - 1344 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BMJ Publishing Group Ltd and European League Against Rheumatism
01.10.2021
Elsevier Limited BMJ Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | ObjectiveTo investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.MethodsEstablished patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.ResultsAlthough healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.ConclusionsIn two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. |
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| AbstractList | To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.
Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.
Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.
In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. ObjectiveTo investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.MethodsEstablished patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.ResultsAlthough healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.ConclusionsIn two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.OBJECTIVETo investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.METHODSEstablished patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.RESULTSAlthough healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.CONCLUSIONSIn two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. |
| Author | Samanovic, Marie Koralov, Sergei B Schett, Georg Castillo, Rochelle Atreya, Raja Reddy, Soumya M Samuels, Jonathan Scher, Jose U Herati, Ramin Mulligan, Mark J Haberman, Rebecca H Solomon, Gary Izmirly, Peter Azar, Natalie Cornelius, Amber R Golden, Brian Neurath, Markus F Abramson, Steven B Tascilar, Koray Tuen, Michael Adhikari, Samrachana Rosenthal, Pamela Blank, Rebecca B Simon, David Rackoff, Paula Allen, Joseph R |
| AuthorAffiliation | 6 Deutsches Zentrum fuer Immuntherapie (DZI) , Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen , Erlangen , Germany 2 NYU Langone Psoriatic Arthritis Center , New York University School of Medicine , New York , New York , USA 10 Department of Medicine , NYU Langone Orthopedic Hospital , New York , New York , USA 7 Department of Pathology , New York University Grossman School of Medicine , New York , New York , USA 1 Division of Rheumatology, Department of Medicine , New York University Grossman School of Medicine , New York , New York , USA 5 Department of Internal Medicine 3 - Rheumatology and Immunology , Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen , Erlangen , Germany 9 Department of Population Health , NYU Grossman School of Medicine , New York , NY , USA 4 New York University Grossman School of Medicine , New York , New York , USA 8 Department of Internal Medicine 1 , Friedrich-Alexander University Erlangen-Nuremb |
| AuthorAffiliation_xml | – name: 7 Department of Pathology , New York University Grossman School of Medicine , New York , New York , USA – name: 11 Rheumatology Research , NYU-NYU Langone Orthopedic Hospital , New York , New York , USA – name: 8 Department of Internal Medicine 1 , Friedrich-Alexander University Erlangen-Nuremberg , Erlangen , Germany – name: 10 Department of Medicine , NYU Langone Orthopedic Hospital , New York , New York , USA – name: 6 Deutsches Zentrum fuer Immuntherapie (DZI) , Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen , Erlangen , Germany – name: 4 New York University Grossman School of Medicine , New York , New York , USA – name: 3 Divison of Infectious Disease and Immunology and NYU Langone Vaccine Center, Department of Medicine , New York University School of Medicine , New York , NY , USA – name: 1 Division of Rheumatology, Department of Medicine , New York University Grossman School of Medicine , New York , New York , USA – name: 5 Department of Internal Medicine 3 - Rheumatology and Immunology , Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen , Erlangen , Germany – name: 9 Department of Population Health , NYU Grossman School of Medicine , New York , NY , USA – name: 2 NYU Langone Psoriatic Arthritis Center , New York University School of Medicine , New York , New York , USA |
| Author_xml | – sequence: 1 givenname: Rebecca H surname: Haberman fullname: Haberman, Rebecca H organization: NYU Langone Psoriatic Arthritis Center, New York University School of Medicine, New York, New York, USA – sequence: 2 givenname: Ramin surname: Herati fullname: Herati, Ramin organization: New York University Grossman School of Medicine, New York, New York, USA – sequence: 3 givenname: David orcidid: 0000-0001-8310-7820 surname: Simon fullname: Simon, David organization: Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 4 givenname: Marie surname: Samanovic fullname: Samanovic, Marie organization: New York University Grossman School of Medicine, New York, New York, USA – sequence: 5 givenname: Rebecca B surname: Blank fullname: Blank, Rebecca B organization: New York University Grossman School of Medicine, New York, New York, USA – sequence: 6 givenname: Michael surname: Tuen fullname: Tuen, Michael organization: New York University Grossman School of Medicine, New York, New York, USA – sequence: 7 givenname: Sergei B surname: Koralov fullname: Koralov, Sergei B organization: Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA – sequence: 8 givenname: Raja surname: Atreya fullname: Atreya, Raja organization: Department of Internal Medicine 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany – sequence: 9 givenname: Koray surname: Tascilar fullname: Tascilar, Koray organization: Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 10 givenname: Joseph R surname: Allen fullname: Allen, Joseph R organization: Divison of Infectious Disease and Immunology and NYU Langone Vaccine Center, Department of Medicine, New York University School of Medicine, New York, NY, USA – sequence: 11 givenname: Rochelle surname: Castillo fullname: Castillo, Rochelle organization: NYU Langone Psoriatic Arthritis Center, New York University School of Medicine, New York, New York, USA – sequence: 12 givenname: Amber R surname: Cornelius fullname: Cornelius, Amber R organization: Divison of Infectious Disease and Immunology and NYU Langone Vaccine Center, Department of Medicine, New York University School of Medicine, New York, NY, USA – sequence: 13 givenname: Paula surname: Rackoff fullname: Rackoff, Paula organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 14 givenname: Gary surname: Solomon fullname: Solomon, Gary organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 15 givenname: Samrachana surname: Adhikari fullname: Adhikari, Samrachana organization: Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA – sequence: 16 givenname: Natalie surname: Azar fullname: Azar, Natalie organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 17 givenname: Pamela surname: Rosenthal fullname: Rosenthal, Pamela organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 18 givenname: Peter surname: Izmirly fullname: Izmirly, Peter organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 19 givenname: Jonathan surname: Samuels fullname: Samuels, Jonathan organization: Department of Medicine, NYU Langone Orthopedic Hospital, New York, New York, USA – sequence: 20 givenname: Brian surname: Golden fullname: Golden, Brian organization: Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA – sequence: 21 givenname: Soumya M surname: Reddy fullname: Reddy, Soumya M organization: NYU Langone Psoriatic Arthritis Center, New York University School of Medicine, New York, New York, USA – sequence: 22 givenname: Markus F surname: Neurath fullname: Neurath, Markus F organization: Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 23 givenname: Steven B orcidid: 0000-0002-0668-6344 surname: Abramson fullname: Abramson, Steven B organization: Rheumatology Research, NYU-NYU Langone Orthopedic Hospital, New York, New York, USA – sequence: 24 givenname: Georg orcidid: 0000-0001-8740-9615 surname: Schett fullname: Schett, Georg organization: Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 25 givenname: Mark J surname: Mulligan fullname: Mulligan, Mark J organization: New York University Grossman School of Medicine, New York, New York, USA – sequence: 26 givenname: Jose U orcidid: 0000-0002-1072-6994 surname: Scher fullname: Scher, Jose U email: jose.scher@nyulangone.org organization: New York University Grossman School of Medicine, New York, New York, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34035003$$D View this record in MEDLINE/PubMed |
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case series from New York publication-title: N Engl J Med doi: 10.1056/NEJMc2009567 – volume: 383 start-page: 1920 year: 2020 article-title: An mRNA Vaccine against SARS-CoV-2 - Preliminary Report publication-title: N Engl J Med doi: 10.1056/NEJMoa2022483 – volume: 11 year: 2020 article-title: Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion publication-title: Nat Commun doi: 10.1038/s41467-020-17703-6 – volume: 80 start-page: 1302 year: 2021 article-title: Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2021-220272 – volume: 51 start-page: 695 year: 2012 article-title: Protective effect of A/H1N1 vaccination in immune-mediated disease--a prospectively controlled vaccination study publication-title: Rheumatology doi: 10.1093/rheumatology/ker389 – year: 2021 article-title: Poor antigen-specific responses to the second BNT162b2 mRNA vaccine dose in SARS-CoV-2-experienced individuals publication-title: medRxiv doi: 10.1101/2021.02.07.21251311 – volume: 13 start-page: R209 year: 2011 article-title: Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor publication-title: Arthritis Res Ther doi: 10.1186/ar3542 – year: 2021 article-title: Early T cell and binding antibody responses are associated with Covid-19 RNA vaccine efficacy onset publication-title: Med doi: 10.1016/j.medj.2021.04.003 – volume: 26 start-page: 1033 year: 2020 article-title: A serological assay to detect SARS-CoV-2 seroconversion in humans publication-title: Nat Med doi: 10.1038/s41591-020-0913-5 – volume: 383 start-page: 2603 year: 2020 article-title: Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine publication-title: N Engl J Med doi: 10.1056/NEJMoa2034577 – volume: 66 start-page: 1016 year: 2014 article-title: Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis publication-title: Arthritis Care Res doi: 10.1002/acr.22246 – volume: 80 start-page: 1302 year: 2021 ident: 10.1136/annrheumdis-2021-220597_bib15 article-title: Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2021-220272 – volume: 383 start-page: 2603 year: 2020 ident: 10.1136/annrheumdis-2021-220597_bib6 article-title: Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine publication-title: N Engl J Med doi: 10.1056/NEJMoa2034577 – volume: 590 start-page: 630 year: 2021 ident: 10.1136/annrheumdis-2021-220597_bib17 article-title: Correlates of protection against SARS-CoV-2 in rhesus macaques publication-title: Nature doi: 10.1038/s41586-020-03041-6 – volume: 383 start-page: 1920 year: 2020 ident: 10.1136/annrheumdis-2021-220597_bib19 article-title: An mRNA Vaccine against SARS-CoV-2 - 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medRxiv. 2021 May 12:2021.05.11.21256917. doi: 10.1101/2021.05.11.21256917. |
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| Snippet | ObjectiveTo investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory... To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases... |
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| SubjectTerms | Antibodies arthritis CD8 antigen Cell activation Coronaviruses COVID-19 COVID-19 vaccines Disease Epidemiology Flow cytometry Immune response (cell-mediated) Immune response (humoral) Immunocompetence Immunogenicity Immunoglobulin G Immunomodulation Infections Inflammatory diseases Influenza Lymphocytes T Methotrexate mRNA mRNA vaccines Patients Proteins Psoriasis psoriatic rheumatoid Rheumatoid arthritis Severe acute respiratory syndrome coronavirus 2 Software Spike protein Steroids Tumor necrosis factor Tumor necrosis factor-TNF Tumors vaccination Vaccine efficacy Vaccines |
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| Title | Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease |
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