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

Key Points Question Is receipt of tumor necrosis factor (TNF) inhibitor monotherapy at the time of COVID-19 diagnosis associated with adverse COVID-19 outcomes compared with other treatment regimens among patients with immune-mediated inflammatory diseases (IMIDs)? Findings In this cohort study of 6077 patients with IMIDs and COVID-19, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, or Janus kinase inhibitor monotherapy were each associated with significantly higher odds of hospitalization or death compared with TNF inhibitor monotherapy. Meaning This study’s findings support the continued use of TNF inhibitor monotherapy among individuals with IMIDs during the pandemic.
Importance Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19–associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures The main outcome was COVID-19–associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P
This cohort study uses data from 3 international registries to examine the association between the receipt of tumor necrosis factor monotherapy and the risk of COVID-19–associated hospitalization or death among adult patients with immune-mediated inflammatory diseases.