TNF Inhibitors and the Risk of Adverse COVID-19 Outcomes in Patients with Immune-Mediated Inflammatory Disease: Pooled Data from Three Global Registries

Zara Izadi¹, Erica Brenner², Satveer Mahil³, Nick Dand⁴, Zenas Yiu⁵, Mark Yates⁴, Ryan Ungaro⁶, Xian Zhang², Manasi Agrawal⁶, Jean-Frederic Colombel⁷, Milena Gianfrancesco¹, Kimme Hyrich⁵, Anja Strangfeld⁸, Loreto Carmona⁹, Elsa Frazão Mateus¹⁰, Saskia Lawson-Tovey⁵, Eva Klingberg¹¹, Giovanna Cuomo¹², Marta Caprioli¹³, Rene-Marc FLIPO¹⁴, Ana Rita Cruz-Machado¹⁵, Carolina Mazeda¹⁶, Rebecca Hasseli¹⁷, Alexander Pfeil¹⁸, Hanns-Martin Lorenz¹⁹, Laura Trupin²⁰, Stephanie Rush¹, Patricia Katz¹, Gabriela Schmajuk¹, Lindsay Jacobsohn²¹, Andrea Seet¹, Samar Al Emadi²², Leanna Wise²³, Emily Gilbert²⁴, Ali Duarte-Garcia²⁵, Maria Valenzuela-Almada²⁶, Carolina Isnardi²⁷, Rosana Quintana²⁷, Enrique Soriano²⁸, Tiffany Hsu²⁹, Kristin D'Silva³⁰, Jeffrey Sparks³¹, Naomi Patel³⁰, Viviane de Souza³², Licia Maria Henrique Mota³³, Ana Paula Reis³⁴, Zachary S. Wallace³⁵, Suleman Bhana³⁶, Wendy Costello³⁷, Rebecca Grainger³⁸, Jonathan Hausmann³⁹, Jean Liew⁴⁰, Emily Sirotich⁴¹, Paul Sufka⁴², Philip Robinson⁴³, Pedro Machado⁴⁴, Christopher Griffiths⁴⁵, Jonathan Barker⁴, Catherine smith⁴, Jinoos Yazdany¹ and Michael Kappelman², ¹University of California San Francisco, San Francisco, CA, ²University of North Carolina at Chapel Hill, Chapel Hill, NC, ³St John’s Institute of Dermatology, London, United Kingdom, ⁴King's College London, London, United Kingdom, ⁵University of Manchester, Manchester, United Kingdom, ⁶Icahn School of Medicine at Mount Sinai, New York, NY, ⁷MD, New York, NY, ⁸Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, ⁹Instituto de Salud Musculoesqueltica (InMusc), Madrid, Spain, ¹⁰Liga Portuguesa Contra as Doenças Reumáticas (LPCDR), Lisbon, Portugal, ¹¹University of Gothenburg, Gothenburg, Sweden and Sahlgrenska University Hospital, Gothenburg, Sweden, ¹²Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy, ¹³IRCCS Humanitas Research Hospital, Milan, Italy, ¹⁴Rheumatology Department, Lille University Hospital, Lille, France, ¹⁵Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Center; Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal, ¹⁶Rheumatology Department - Centro Hospitalar do Baixo Vouga and Ibimed, Institute for Biomedicine, University of Aveiro, Aveiro, Portugal, ¹⁷Justus-Liebig-University Giessen, Bad Nauheim, Germany, ¹⁸Friedrich Schiller University Jena, Jena, Germany, ¹⁹University Hospital Heidelberg Germany, Heidelberg, Germany, ²⁰UC San Francisco, San Francisco, CA, ²¹University of California San Francisco, Antioch, CA, ²²Hamad medical corporation, Doha, Qatar, ²³LAC+USC/Keck Medicine of USC, Pasadena, CA, ²⁴Mayo Clinic, Jacksonville, FL, ²⁵Mayo Clinic, Rochester, MN, ²⁶Division of Rheumatology, Mayo Clinic, Rochester, MN, ²⁷Argentine Society of Rheumatology, Buenos Aires, Argentina, ²⁸Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ²⁹Brigham and Women's Hospital, Jamaica Plain, MA, ³⁰Massachusetts General Hospital, Boston, MA, ³¹Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, ³²UFJF, JUIZ DE FORA, Brazil, ³³Universidade de Brasília, Brasilia, Brazil, ³⁴Centro Universitrio de Braslia- UniCEUB, Brasilia, Brazil, ³⁵Harvard Medical School, Boston, MA, ³⁶Crystal Run Health, Montvale, NJ, ³⁷Irish Children's Arthritis Network, Bansha, Ireland, ³⁸University of Otago, Wellington, New Zealand, ³⁹Boston Children's Hospital / Beth Israel Deaconess Medical Center, Cambridge, MA, ⁴⁰Boston University, Boston, MA, ⁴¹McMaster University, Hamilton, ON, Canada, ⁴²HealthPartners, Eagan, MN, ⁴³University of Queensland School of Clinical Medicine, Brisbane, Australia, ⁴⁴Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, United Kingdom, ⁴⁵University of Manchester, Manchester Centre for Dermatology Research, Manchester, United Kingdom

Meeting: ACR Convergence 2021

Keywords: Anti-TNF Drugs, COVID-19, registry

Session Information

Date: Saturday, November 6, 2021

Title: Epidemiology & Public Health Poster I: COVID-19 & Vaccination (0084–0117)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: While tumor necrosis factor inhibitors (TNFi) are widely prescribed globally due to their high efficacy across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 on individuals with IMIDs receiving TNFi remains poorly understood. The objective of this study was to assess the association between TNFi monotherapy and COVID-19-related hospitalization or death among individuals with IMIDs, compared to other commonly prescribed immunomodulatory regimens.

Methods: We used data from three global COVID-19 registries of individuals with rheumatic diseases, IBD, and psoriasis. Healthcare providers reported COVID-19 outcomes and demographic and clinical characteristics of individuals with IMIDs with confirmed or suspected COVID-19. We included resolved adult COVID-19 cases with a diagnosis of inflammatory arthritis (IA), IBD, or psoriasis reported on or before February 1st, 2021. Medication exposure was defined as a categorical variable with the following categories: TNFi monotherapy (reference), TNFi in combination with MTX, TNFi in combination with AZA/6-mercaptopurine (AZA/6MP), MTX monotherapy, AZA/6MP monotherapy, and janus kinase inhibitor (JAKi) monotherapy. The outcome was COVID-19-related hospitalization or death. Registry-level analyses and a pooled analysis of data across the three registries were conducted using multilevel multivariable mixed-effects logistic regression, adjusting for demographics, clinical characteristics, comorbidities, concomitant immunomodulatory medications, and accounting for country, calendar-month, and registry-level correlations. In a sensitivity analysis we excluded patients whose COVID-19 diagnosis was based on symptoms alone.

Results: A total of 6,077 cases from 74 countries were included. Mean (SD) age was 48.8 (16.5) years and 58.6% were female (Table). The most common diagnoses were rheumatoid arthritis (35.3%) and Crohn’s disease (25.3%). Over one-fifth (21.3%) of cases were hospitalized for COVID-19 and 3.1% died. In the pooled analysis, compared with TNFi monotherapy, higher odds of hospitalization or death were observed with TNFi in combination with AZA/6MP (odds ratio: 1.7, 95% CI: 1.2-2.6), AZA/6MP monotherapy (1.8, 1.3-2.6), MTX monotherapy (2.0, 1.6-2.6), and JAKi monotherapy (1.8, 1.2-2.7). ORs obtained from registry-specific analyses were generally in the same direction and of similar magnitude as those obtained from the pooled analysis (Figure). Similar findings were obtained after excluding patients whose COVID-19 diagnosis was based on symptoms alone.

Conclusion: Among individuals with IMIDs, TNFi monotherapy is associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory regimens. These data can help inform treatment decisions for individuals with IMIDs during the pandemic.

*Categories are mutually exclusive. **Presumptive diagnosis was based on symptoms alone. Abbreviations: GRA: Global Rheumatology Alliance; SECURE-IBD: Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease; PsoProtect: Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID_19 Infection. JAKi: janus kinase inhibitor; 6MP: 6-mercaptopurine; TNFi: tumor necrosis factor inhibitor; HCQ: hydroxychloroquine; GC: glucocorticoid; IA: inflammatory arthritis; IBD: inflammatory bowel disease.

TNFi monotherapy is the reference category. Pooled sensitivity analysis excludes COVID_19 diagnoses based on symptoms alone. Odds ratios derived using multilevel multivariable mixed-effects logistic regression. Registry-level analyses adjusted for demographics, clinical characteristics, comorbidities, concomitant medications, and accounted for country and calendar-month correlations. Pooled analyses additionally accounted for registry-level correlations. Abbreviations: MTX: methotrexate; TNFi: tumor necrosis factor inhibitor; AZA/6MP: azathioprine/6-mercaptopurine; JAKi: janus kinase inhibitor. N = 3,523 (GRA); 2,336 (SECURE-IBD); 300 (PsoProtect); 6,159 (Pooled); 5,223 (Pooled, sensitivity analysis).

Disclosures: Z. Izadi, None; E. Brenner, None; S. Mahil, Lilly, 5, AbbVie, 5, Sanofi, 5, Novartis, 5, UCB, 5; N. Dand, None; Z. Yiu, None; M. Yates, UCB, 6, Abbvie, 6; R. Ungaro, AbbVie, 2, Bristol Myers Squibb, 2, Janssen, 6, Pfizer, 2, 6, Takeda, 1, 5; X. Zhang, None; M. Agrawal, None; J. Colombel, Abbvie, 2, 5, 6, Janssen, 2, 5, Takeda, 2, 5, 6, Amgen, 2, 6, Allergan, 6, Inc. Ferring Pharmaceuticals, 6, Shire, 2, 6, Arena Pharmaceuticals, 2, Boehringer Ingelheim, 2, Celgene Corporation, 2, Celltrion, 2, Eli Lilly, 2, Enterome, 2, Ferring Pharmaceuticals, 2, Genentech, 2, Landos, 2, Ipsen, 2, Medimmune, 2, Merck, 2, Novartis, 2, Pfizer, 2, Tigenix, 2, Viela bio, 2, Intestinal Biotech Development, 11, Genfit, 11; M. Gianfrancesco, None; K. Hyrich, Abbvie, 6, Pfizer, 5, BMS, 5; A. Strangfeld, Pfizer, 6, Roche, 6, MSD, 6, BMS, 6, Abbvie, 6, Celltrion, 6; L. Carmona, None; E. Frazão Mateus, Boehringer Ingelheim, 6, Pfizer, 5, 12, Non-financial, Lilly Portugal, 5, Sanofi, 5, AbbVie, 5, Novartis, 5, Grünenthal. SA., 5, MSD, 5, Celgene, 5, Medac, 5, Janssen-Cilag, 5, Pharmakern, 5, GAfPA, 5; S. Lawson-Tovey, None; E. Klingberg, Eli Lilly, 6, Novartis, 2, Roche, 5; G. Cuomo, None; M. Caprioli, None; R. FLIPO, Novartis, 2, 6, Lilly, 2, 6, Abbvie, 2, 6, Pfizer, 2, 6, MSD, 2, 6; A. Cruz-Machado, MSD, 5; C. Mazeda, None; R. Hasseli, Pfizer, Novartis, Medac, Abbvie, Galapagos, BMS, Biogen, Takeda, Roche/Chugai, Janssen, Amgen, 1, 2, 6, Pfizer, 5; A. Pfeil, None; H. Lorenz, None; L. Trupin, None; S. Rush, None; P. Katz, None; G. Schmajuk, None; L. Jacobsohn, None; A. Seet, None; S. Al Emadi, None; L. Wise, None; E. Gilbert, None; A. Duarte-Garcia, None; M. Valenzuela-Almada, None; C. Isnardi, Pfizer, 5, Elea Phoenix, 5, Abbvie, 5, Bristol-Myers Squibb, 6; R. Quintana, None; E. Soriano, AbbVie, 1, 5, 6, Amgen, 6, Bristol Myers Squibb, 6, Janssen, 1, 5, 6, Eli Lilly, 6, Novartis, 1, 5, 6, Pfizer, 5, 6, Roche, 1, 5, 6, UCB, 5, 6; T. Hsu, None; K. D'Silva, None; J. Sparks, Bristol-Myers Squibb, 2, Gilead, 2, Inova Diagnostics, 2, Optum, 2, Pfizer, 2; N. Patel, None; V. de Souza, None; L. Mota, Janssen, 1, 6, Pfizer, 6, UCB, 6, Abbvie, 6, Boehringer Ingelheim, 6, Sandoz, 6, Amgen, 6, GSK, 1, Lilly, 6; A. Reis, None; Z. Wallace, BMS, 5, Sanofi, 5, Viela Bio, 2, MedPace, 2; S. Bhana, Amgen, 1, Novartis, 1, Horizon, 1, Pfizer, 1, AbbVie, 1; W. Costello, None; R. Grainger, Pfizer New Zealand, 6, 12, support to travel to conference, Jansenn Autralia, 6, 12, travel to symposia, AbbVie New Zealand, 6, Cornerstones, 6, novartis, 1; J. Hausmann, Novartis, 2, Biogen, 2, Pfizer, 2; J. Liew, Pfizer, 5; E. Sirotich, None; P. Sufka, Wiley Publishing, 6; P. Robinson, Abbvie, 1, Novartis, 1, 5, 6, Atom Biosciences, 1, Janssen, 5, 6, Eli Lilly, 1, 2, 6, Gilead, 6, UCB Pharma, 1, 5, 6, Pfizer, 1, 5, 6, Roche, 6; P. Machado, Abbvie, 6, BMS, 6, Celgene, 6, Eli Lilly, 2, Janssen, 2, MSD, 6, Galapagos, 6, Novartis, 2, 6, Pfizer, 6, Roche, 6, UCB, 2, 6, Orphazyme, 5, 6; C. Griffiths, AbbVie, 5, 6, Amgen, 5, 6, Almirall, 5, 6, Bristol-Myers Squibb, 5, 6, Boehringer Ingelheim, 5, 6, Celgene, 5, 6, Janssen, 5, 6, LEO Pharma, 5, 6, Eli Lilly, 5, 6, Novartis, 5, 6, Pfizer, 5, 6, Sun Pharma, 5, 6, UCB Pharma, 5, 6; J. Barker, Abbvie, 5, 6, Almirall, 5, 6, Amgen, 5, 6, Boehringer-Ingelheim, 5, 6, Bristol-Myers Squibb, 5, 6, Celgene, 5, 6, Janssen, 5, 6, Leo, 5, 6, Lilly, 5, 6, Novartis, 5, 6, Samsung, 5, 6, Sun Pharma, 5, 6; C. smith, Abbvie, 12, Departmental research funding, Novartis, 12, Departmental research funding, Pfizer, 12, Departmental research funding, Sanofi, 12, Departmental research funding, Horizon 2020, 12, CHS has served as an investigator on Medical Research Council– and Horizon 2020–funded consortia with industry partners (see psort.org.uk and biomap—imi.eu), SOBI, 12, SOBI provided the drug for a National Institute for Health Research–funded trial in pustular psoriasis; J. Yazdany, Pfizer, 2, Astra Zeneca, 5, Eli Lilly, 2, University of California, San Francisco, 3; M. Kappelman, Abbvie, 2, 5, Janssen, 2, 5, Lilly, 2, 5, Takeda, 2, 5, Pfizer, 2, 5.

To cite this abstract in AMA style:

Izadi Z, Brenner E, Mahil S, Dand N, Yiu Z, Yates M, Ungaro R, Zhang X, Agrawal M, Colombel J, Gianfrancesco M, Hyrich K, Strangfeld A, Carmona L, Frazão Mateus E, Lawson-Tovey S, Klingberg E, Cuomo G, Caprioli M, FLIPO R, Cruz-Machado A, Mazeda C, Hasseli R, Pfeil A, Lorenz H, Trupin L, Rush S, Katz P, Schmajuk G, Jacobsohn L, Seet A, Al Emadi S, Wise L, Gilbert E, Duarte-Garcia A, Valenzuela-Almada M, Isnardi C, Quintana R, Soriano E, Hsu T, D'Silva K, Sparks J, Patel N, de Souza V, Mota L, Reis A, Wallace Z, Bhana S, Costello W, Grainger R, Hausmann J, Liew J, Sirotich E, Sufka P, Robinson P, Machado P, Griffiths C, Barker J, smith C, Yazdany J, Kappelman M. TNF Inhibitors and the Risk of Adverse COVID-19 Outcomes in Patients with Immune-Mediated Inflammatory Disease: Pooled Data from Three Global Registries [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/tnf-inhibitors-and-the-risk-of-adverse-covid-19-outcomes-in-patients-with-immune-mediated-inflammatory-disease-pooled-data-from-three-global-registries/. Accessed .

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