Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
Authors: Zara Izadi, Erica J. Brenner, Satveer K. Mahil, Nick Dand, Zenas Z. N. Yiu, Mark Yates, Ryan C. Ungaro, Xian Zhang, Manasi Agrawal, Jean-Frederic Colombel, Milena A. Gianfrancesco, Kimme L. Hyrich, Anja Strangfeld, Loreto Carmona, Elsa F. Mateus, Saskia Lawson-Tovey, Eva Klingberg, Giovanna Cuomo, Marta Caprioli, Ana Rita Cruz-Machado, Ana Carolina Mazeda Pereira, Rebecca Hasseli, Alexander Pfeil, Hanns-Martin Lorenz, Bimba Franziska Hoyer, Laura Trupin, Stephanie Rush, Patricia Katz, Gabriela Schmajuk, Lindsay Jacobsohn, Andrea M. Seet, Samar Al Emadi, Leanna Wise, Emily L. Gilbert, Alí Duarte-García, Maria O. Valenzuela-Almada, Carolina A. Isnardi, Rosana Quintana, Enrique R. Soriano, Tiffany Y-T. Hsu, Kristin M. D’Silva, Jeffrey A. Sparks, Naomi J. Patel, Ricardo Machado Xavier, Claudia Diniz Lopes Marques, Adriana Maria Kakehasi, René-Marc Flipo, Pascal Claudepierre, Alain Cantagrel, Philippe Goupille, Zachary S. Wallace, Suleman Bhana, Wendy Costello, Rebecca Grainger, Jonathan S. Hausmann, Jean W. Liew, Emily Sirotich, Paul Sufka, Philip C. Robinson, Pedro M. Machado, Christopher E. M. Griffiths, Jonathan N. Barker, Catherine H. Smith, Jinoos Yazdany, Michael D. Kappelman, Hervé Bachelez, Francesca Capon, Bola Coker, Claudia De La Cruz, Kayleigh J Mason, Paola Di Meglio, Joel M Gelfand, Paolo Gisondi, Lars Iversen, Denis Jullien, Jo Lambert, Sinéad M Langan, Helen McAteer, Freya Meynell, Lucy Moorhead, Luigi Naldi, Luis Puig, Nick J Reynolds, Phyllis Spuls, Tiago Torres, Teresa Tsakok, Alexandra Vincent, Richard B Warren, Hoseah Waweru, Siew Ng, Richard Gearry, Walter Reinisch, Jean-Francois Rahier, James Lewis, Gilaad Kaplan, Flavio Steinwurz, Michele Kissous-Hunt, Irene Modesto, Marishka Konings, Brahim Dahou, Gimena Gómez, Karen Roberts, Roberto M Baez, Vanessa V Castro Coello, María J Haye Salinas, Federico N Maldonado, Alvaro A Reyes, Gelsomina Alle, Romina Tanten, Hernán Maldonado Ficco, Romina Nieto, Carla Gobbi, Yohana Tissera, Cecilia Pisoni, Alba Paula, Juan A Albiero, Maria M Schmid, Micaela Cosatti, Maria J Gamba, Carlevaris Leandro, María A Cusa, Noelia German, Veronica Bellomio, Lorena Takashima, Mariana Pera, Karina Cogo, Maria S Gálvez Elkin, María A Medina, Veronica Savio, Romina Rojas Tessel, Rodolfo P Alamino, Marina L Werner, Sofía Ornella, Luciana Casalla, Maria de la Vega, María Severina, Mercedes García, Luciana Gonzalez Lucero, Cecilia Romeo, Sebastián Moyano, Tatiana Barbich, Ana Bertoli, Andrea Baños, Sandra Petruzzelli, Carla Matellan, Silvana Conti, Maria A Lazaro, Gustavo F Rodriguez Gil, Fabian Risueño, Maria I Quaglia, Julia Scafati, Natalia L Cuchiaro, Jonathan E Rebak, Susana I Pineda, María E Calvo, Eugenia Picco, Josefina G Yanzi, Pablo Maid, Debora Guaglianone, Julieta S Morbiducci, Sabrina Porta, Natalia Herscovich, José L Velasco Zamora, Boris Kisluk, Maria S Castaños Menescardi, Rosana Gallo, María V Martire, Carla Maldini, Cecilia Goizueta, Sabrina S de la Vega Fernandez, Carolina Aeschlimann, Gisela Subils, Eva Rath, Yves Piette, Mieke Devinck, Bea Maeyaert, Francinne Machado Ribeiro, Sandra L Euzebio Ribeiro, Marcelo Pinheiro, Sebastián Ibáñez, Anne-Marie Chassin Trubert, Lingli Dong, Lui Cajas, Marko Barešić, Branimir Anić, Melanie-Ivana Čulo, Tea A Pavelić, Kristina K Stranski, Boris Karanovic, Jiri Vencovsky, Marta Píchová, Maria Filkova, Hesham Hamoud, Dimitrios Vassilopoulos, Gabriela M Guzman Melgar, Ho So, Márta Király, Mahdi Vojdanian, Alexandra Balbir Gurman, Fatemah Abutiban, Julija Zepa, Inita Bulina, Loreta Bukauskiene, Beatriz E Zazueta Montiel , Angel A Castillo Ortiz, Erick Zamora Tehozol, David Vega Morales , Diana Cervántes Rosete, Eduardo Martín Nares, Tatiana S Rodriguez Reyna, Marina Rull Gabayet, Deshiré Alpízar Rodríguez, Fedra Irazoque, Xochitl Jimenez, Lenny Geurts van Bon, Theo Zijlstra, Monique Hoekstra, Nasra Al Adhoubi, Babur Salim, Enrique Giraldo, Ariel Salinas, Manuel Ugarte Gil, Jarosław Nowakowski, Richard Conway, Rachael Flood, Geraldine McCarthy, Ioana Felea, Ileana Filipescu, Simona Rednic, Laura Groseanu, Maria M Tamas, Vanda Mlynarikova, Martina Skamlova, Martin Zlnay, Dagmar Mičeková, Lubica Capova, Zelmira Macejova, Emőke Šteňová, Helena Raffayova, Gabriela Belakova, Eva Strakova, Marieta Senčarová, Soňa Žlnayová, Anna Sabová, Daniela Spisakova, Mária Oetterová, Olga Lukacova, Martina Bakosova, Alojzija Hocevar, Natalia de la Torre Rubio, Juan J Alegre Sancho, Montserrat Corteguera Coro, Juan C Cobeta Garcia, Maria C Torres Martin, Jose Campos, Jose A Gomez Puerta, Gozd K Yardımcı, Servet Akar, Ozan C Icacan, Selda ÇELİK, Viktoriia Vasylets, Su-Ann Yeoh, Claire Vandevelde, Sasha Dunt, Jane Leeder, Elizabeth Macphie, Rosaria Salerno, Christine Graver, Katie Williams, Sheila O'Reilly, Kirsty Devine, Jennifer Tyler, Elizabeth Warner, James Pilcher, Samir Patel, Elena Nikiphorou, Laura Chadwick, Caroline M Jones, Beverley Harrison, Lucy Thornton, Diana O'Kane, Lucia Fusi, Audrey Low, Sarah Horton, Shraddha Jatwani, Sara Baig, Hammad Bajwa, Vernon Berglund, Angela Dahle, Walter Dorman, Jody Hargrove, Maren Hilton, Nicholas Lebedoff, Susan Leonard, Jennifer Morgan, Emily Pfeifer, Archibald Skemp, Jeffrey Wilson, Anne Wolff, Eduardo Cepeda, Derrick Todd, Denise Hare, Cassandra Calabrese, Christopher Adams, Arezou Khosroshahi, Adam Kilian, Douglas White, Melanie Winter, Theodore Fields, Caroline Siegel, Nicole Daver, Melissa Harvey, Neil Kramer, Concetta Lamore, Suneya Hogarty, Karen Yeter, Faizah Siddique, Byung Ban, Tamar Tanner, Eric Ruderman, William Davis, Robert Quinet, Evangeline Scopelitis, Karen Toribio, Tameka Webb Detiege, Jerald Zakem, Khurram Abbass, Gilbert Kepecs, Lilliam Miranda, Michael Guma, Ammar Haikal, Sushama Mody, Daric Mueller, Arundathi Jayatilleke, JoAnn Zell, Alison Bays, Kathryn Dao, Fatemeh Ezzati, Deborah Parks, David Karp, Guillermo Quiceno
Journal: JAMA Network Open (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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;<i>P</i> = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61;<i>P</i> = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56;<i>P</i> &lt; .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73;<i>P</i> = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63;<i>P</i> = .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. <h3>Conclusions and Relevance</h3> 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.