Association between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death among Patients with Immune-Mediated Inflammatory Disease and COVID-19
Creators: name: Claudepierre, P.
name: Yates, M.
name: Sirotich, E.
name: Costello, W.
name: Strangfeld, A.
name: Barker, J.N.
name: Cruz-Machado, A.R.
name: Dand, N.
name: Izadi, Z.
name: Mazeda Pereira, A.C.
name: Bhana, S.
name: Liew, J.W.
name: Goupille, P.
name: Mateus, E.F.
name: Kakehasi, A.M.
name: Schmajuk, G.
name: Brenner, E.J.
name: Cantagrel, A.
name: Cuomo, G.
name: Valenzuela-Almada, M.O.
name: Marques, C.D.L.
name: Patel, N.J.
name: Carmona, L.
name: Hasseli, R.
name: Wise, L.
name: Kappelman, M.D.
name: Rush, S.
name: Flipo, R.-M.
name: Xavier, R.M.
name: Robinson, P.C.
name: Ungaro, R.C.
name: Lorenz, H.-M.
name: Trupin, L.
name: Soriano, E.R.
name: Yiu, Z.Z.N.
name: Katz, P.
name: Gilbert, E.L.
name: Grainger, R.
name: Jacobsohn, L.
name: Al Emadi, S.
name: Hsu, T.Y.-T.
name: Hyrich, K.L.
name: Seet, A.M.
name: Sufka, P.
name: Zhang, X.
name: D&apos;Silva, K.M.
name: Caprioli, M.
name: Lawson-Tovey, S.
name: Wallace, Z.S.
name: Gianfrancesco, M.A.
name: Smith, C.H.
name: Klingberg, E.
name: Griffiths, C.E.M.
name: Duarte-García, A.
name: Isnardi, C.A.
name: Sparks, J.A.
name: Machado, P.M.
name: Hoyer, B.F.
name: Yazdany, J.
name: Agrawal, M.
name: Colombel, J.-F.
name: Mahil, S.K.
name: Pfeil, A.
name: Quintana, R.
name: Hausmann, J.S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2021

description: 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 <.001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P =.004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P =.33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.