Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Mortality Among Patients With Immune-Mediated Inflammatory Disease and COVID-19

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Importance: While tumor necrosis factor inhibitors (TNFi) are widely prescribed globally due to their high efficacy at ameliorating shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 on individuals with IMIDs receiving TNFi remains poorly understood.
Objective: To compare the association between TNFi monotherapy and COVID-19-related hospitalization or death among individuals with IMIDs, with other commonly prescribed immunomodulatory regimens.
Design: Pooled analysis using data from three global COVID-19 registries of individuals with rheumatic diseases, inflammatory bowel disease (IBD), and psoriasis, from March 12, 2020, to February 1, 2021.
Setting: Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs diagnosed with confirmed or suspected COVID-19 using online data entry portals.
Participants: Adults (≥18 years) with a diagnosis of inflammatory arthritis, IBD, or psoriasis.
Exposure(s): Exposure categories included: tumor necrosis factor inhibitor (TNFi) monotherapy (reference), TNFi in combination with methotrexate, TNFi in combination with azathioprine/6-mercaptopurine, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, janus kinase inhibitor (JAKi) monotherapy.
Main outcome(s) and Measure(s): COVID-19-related hospitalization or death. Registry-level analyses and a pooled analysis of data across the registries were conducted using multilevel multivariable logistic regression, adjusting for demographics and clinical characteristics and accounting for country, calendar month and registry-level correlations.
Results: A total of 6,077 patients from 74 countries were included. Mean (SD) age was 48.8 (16.5) years and 58.6% were female. The most common IMID diagnoses were rheumatoid arthritis (35.3%) and Crohn’s disease (25.3%). A total of 1,297 patients were hospitalized and 189 died. In the pooled analysis, compared with TNFi monotherapy, higher odds of hospitalization or death were observed with TNFi in combination with azathioprine/6-mercaptopurine (odds ratio: 1.74, 95% CI: 1.17-2.58), azathioprine/6-mercaptopurine monotherapy (1.84, 1.30-2.61), methotrexate monotherapy (2.0, 1.57-2.56), and JAKi monotherapy (1.82, 1.21-2.73), but not with TNFi in combination with methotrexate (1.18, 0.85-1.63). Similar findings were obtained in analyses that accounted for potential reporting bias and after excluding COVID-19 diagnoses based on symptoms alone.
Conclusions and Relevance: In this cohort study, among individuals with IMIDs, TNFi monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory regimens.
Original languageEnglish
JournalJAMA Network Open
Early online date18 Oct 2021
Publication statusPublished - 18 Oct 2021


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