Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study
Objective Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants’ impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required.Design We perfor...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/2/e077408.full |
| _version_ | 1797269959015923712 |
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| author | Tine Jess Anton Pottegård Jesper Hallas Gry Poulsen Rahma Elmahdi Daniel Ward Martin T Ernst |
| author_facet | Tine Jess Anton Pottegård Jesper Hallas Gry Poulsen Rahma Elmahdi Daniel Ward Martin T Ernst |
| author_sort | Tine Jess |
| collection | DOAJ |
| description | Objective Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants’ impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required.Design We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed.Setting This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021.Results Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID.Conclusion Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks. |
| first_indexed | 2024-03-07T23:04:25Z |
| format | Article |
| id | doaj.art-ad459a284f3b4ecdb7dee3e94d1bf3fc |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-25T01:56:39Z |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj.art-ad459a284f3b4ecdb7dee3e94d1bf3fc2024-03-07T17:10:09ZengBMJ Publishing GroupBMJ Open2044-60552024-02-0114210.1136/bmjopen-2023-077408Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort studyTine Jess0Anton Pottegård1Jesper Hallas2Gry Poulsen3Rahma Elmahdi4Daniel Ward5Martin T Ernst6Department of Clinical Medicine, Aalborg Universitet, Copenhagen, DenmarkClinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Syddanmark, DenmarkClinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Syddanmark, DenmarkDepartment of Clinical Medicine, Aalborg Universitet, Copenhagen, DenmarkDepartment of Clinical Medicine, Aalborg Universitet, Copenhagen, DenmarkDepartment of Clinical Medicine, Aalborg Universitet, Copenhagen, DenmarkClinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Syddanmark, DenmarkObjective Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants’ impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required.Design We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed.Setting This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021.Results Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID.Conclusion Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks.https://bmjopen.bmj.com/content/14/2/e077408.full |
| spellingShingle | Tine Jess Anton Pottegård Jesper Hallas Gry Poulsen Rahma Elmahdi Daniel Ward Martin T Ernst Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study BMJ Open |
| title | Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study |
| title_full | Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study |
| title_fullStr | Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study |
| title_full_unstemmed | Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study |
| title_short | Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study |
| title_sort | impact of immunosuppressive therapy on sars cov 2 mrna vaccine effectiveness in patients with immune mediated inflammatory diseases a danish nationwide cohort study |
| url | https://bmjopen.bmj.com/content/14/2/e077408.full |
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