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JAMA Netw Open
. 2021 Oct 1;4(10):e2129639.
doi: 10.1001/jamanetworkopen.2021.29639.
Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
Zara Izadi 1 2 , Erica J Brenner 3 , Satveer K Mahil 4 5 , Nick Dand 6 7 , Zenas Z N Yiu 8 9 , Mark Yates 10 , Ryan C Ungaro 11 , Xian Zhang 12 , Manasi Agrawal 11 , Jean-Frederic Colombel 11 , Milena A Gianfrancesco 2 , Kimme L Hyrich 13 14 15 , Anja Strangfeld 16 , Loreto Carmona 17 , Elsa F Mateus 18 19 , Saskia Lawson-Tovey 14 15 20 , Eva Klingberg 21 , Giovanna Cuomo 22 , Marta Caprioli 23 , Ana Rita Cruz-Machado 24 25 , Ana Carolina Mazeda Pereira 26 , Rebecca Hasseli 27 , Alexander Pfeil 28 , Hanns-Martin Lorenz 29 , Bimba Franziska Hoyer 30 31 , Laura Trupin 2 , Stephanie Rush 2 , Patricia Katz 2 , Gabriela Schmajuk 2 32 , Lindsay Jacobsohn 2 , Andrea M Seet 2 , Samar Al Emadi 33 , Leanna Wise 34 , Emily L Gilbert 35 , Alí Duarte-García 36 37 , Maria O Valenzuela-Almada 36 , Carolina A Isnardi 38 , Rosana Quintana 38 , Enrique R Soriano 39 , Tiffany Y-T Hsu 40 41 , Kristin M D'Silva 41 42 , Jeffrey A Sparks 40 41 , Naomi J Patel 41 43 , Ricardo Machado Xavier 44 , Claudia Diniz Lopes Marques 45 , Adriana Maria Kakehasi 46 , René-Marc Flipo 47 , Pascal Claudepierre 48 49 , Alain Cantagrel 50 , Philippe Goupille 51 52 , Zachary S Wallace 41 42 , Suleman Bhana 53 , Wendy Costello 54 , Rebecca Grainger 55 , Jonathan S Hausmann 56 57 , Jean W Liew 58 , Emily Sirotich 59 60 , Paul Sufka 61 , Philip C Robinson 62 63 , Pedro M Machado 64 65 66 , Christopher E M Griffiths 8 9 , Jonathan N Barker 67 , Catherine H Smith 4 5 , Jinoos Yazdany 2 , Michael D Kappelman 3 , Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA)
Collaborators, Affiliations
- PMID: 34661663
- DOI: 10.1001/jamanetworkopen.2021.29639
Abstract
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.