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

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To identify the key insights or developments described in this article
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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.

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.

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Article Information

Accepted for Publication: August 4, 2021.

Published: October 18, 2021. doi:10.1001/jamanetworkopen.2021.29639

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Izadi Z et al. JAMA Network Open.

Corresponding Author: Zara Izadi, MPharm, MAS, Department of Epidemiology and Biostatistics, University of California, San Francisco, 550 16th St, 2nd Fl, San Francisco, CA 94158 (zara.izadi@ucsf.edu); Erica J. Brenner, MD, Division of Pediatric Gastroenterology, Department of Pediatrics, University of North Carolina at Chapel Hill, 333 S Columbia St, 247 MacNider Hall, CB# 7229, Chapel Hill, NC 27599 (erica.brenner@unchealth.unc.edu).

Author Contributions: Ms Izadi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Ms Izadi and Dr Brenner share first authorship, and Drs Yazdany and Kappelman share senior authorship.

Concept and design: Izadi, Brenner, Mahil, Yiu, Yates, Hyrich, Carmona, Cuomo, Hasseli, Lorenz, Trupin, Katz, Al Emadi, Wise, Quintana, Wallace, Bhana, Costello, Grainger, Hausmann, Sufka, Robinson, Machado, Barker, Smith, Yazdany, Kappelman.

Acquisition, analysis, or interpretation of data: Izadi, Brenner, Mahil, Dand, Yiu, Ungaro, Zhang, Agrawal, Colombel, Gianfrancesco, Hyrich, Strangfeld, Mateus, Lawson-Tovey, Klingberg, Caprioli, Cruz-Machado, Mazeda Pereira, Pfeil, Lorenz, Hoyer, Trupin, Rush, Schmajuk, Jacobsohn, Seet, Al Emadi, Wise, Gilbert, Duarte-García, Valenzuela-Almada, Isnardi, Soriano, Hsu, D’Silva, Sparks, Patel, Xavier, Marques, Kakehasi, Flipo, Claudepierre, Cantagrel, Goupille, Wallace, Grainger, Hausmann, Liew, Sirotich, Sufka, Machado, Griffiths, Barker, Smith, Yazdany, Kappelman.

Drafting of the manuscript: Izadi, Brenner, Mahil, Yiu, Cuomo, Mazeda Pereira, Lorenz, Wise, Valenzuela-Almada, Quintana, Sirotich, Barker, Yazdany, Kappelman.

Critical revision of the manuscript for important intellectual content: Izadi, Brenner, Mahil, Dand, Yates, Ungaro, Zhang, Agrawal, Colombel, Gianfrancesco, Hyrich, Strangfeld, Carmona, Mateus, Lawson-Tovey, Klingberg, Caprioli, Cruz-Machado, Hasseli, Pfeil, Lorenz, Hoyer, Trupin, Rush, Katz, Schmajuk, Jacobsohn, Seet, Al Emadi, Wise, Gilbert, Duarte-García, Isnardi, Soriano, Hsu, D’Silva, Sparks, Patel, Xavier, Marques, Kakehasi, Flipo, Claudepierre, Cantagrel, Goupille, Wallace, Bhana, Costello, Grainger, Hausmann, Liew, Sirotich, Sufka, Robinson, Machado, Griffiths, Barker, Smith, Yazdany, Kappelman.

Statistical analysis: Izadi, Brenner, Yiu, Zhang, Trupin, Seet, Flipo.

Obtained funding: Ungaro, Hyrich, Marques, Bhana, Robinson, Smith, Yazdany, Kappelman.

Administrative, technical, or material support: Mahil, Dand, Yiu, Agrawal, Gianfrancesco, Hyrich, Lawson-Tovey, Cuomo, Mazeda Pereira, Hasseli, Hoyer, Rush, Jacobsohn, Duarte-García, Quintana, Hsu, D’Silva, Sparks, Marques, Flipo, Wallace, Bhana, Hausmann, Liew, Sufka, Robinson, Machado, Yazdany, Kappelman.

Supervision: Agrawal, Colombel, Pfeil, Katz, Schmajuk, Xavier, Marques, Goupille, Bhana, Grainger, Robinson, Barker, Smith, Yazdany, Kappelman.

Conflict of Interest Disclosures: Dr Brenner reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Mahil reported receiving grants from AbbVie, Celgene, Eli Lilly and Company, Janssen-Cilag, Novartis, Sanofi, and UCB outside the submitted work. Dr Yates reported receiving personal fees from AbbVie and UCB. Dr Ungaro reported receiving personal fees from AbbVie, Bristol Myers Squibb, Janssen Pharmaceuticals, and Pfizer and nonfinancial support from Takeda Pharmaceutical during the conduct of the study. Dr Agrawal reported receiving grants from the Dickler Family Fund, the Helmsley Charitable Trust, and the New York Community Trust during the conduct of the study. Dr Colombel reported receiving grants from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Pharm, Eli Lilly and Company, Genentech, the Helmsley Charitable Trust, Janssen Pharmaceuticals, Pfizer, and Takeda Pharmaceutical during the conduct of the study; grants from AbbVie, Janssen Pharmaceuticals, and Takeda Pharmaceutical; and personal fees from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring Pharmaceuticals, Galmed Pharmaceuticals, GlaxoSmithKline, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Landos Biopharma, Otsuka Pharmaceutical, Pfizer, Prometheus Biosciences, Sanofi, Takeda Pharmaceutical, and TiGenix outside the submitted work. Dr Gianfrancesco reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases outside the submitted work. Dr Hyrich reported receiving grants from the European Alliance of Associations for Rheumatology during the conduct of the study; grants from Bristol Myers Squibb and Pfizer; and personal fees from AbbVie outside the submitted work. Dr Strangfeld reported receiving grants from AbbVie, Amgen, Bristol Myers Squibb, Celltrion Pharm, Eli Lilly and Company, Fresenius Kabi, Gilead Sciences, Hexal, Merck Sharp & Dohme, Mylan/Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB and personal fees from AbbVie, Bristol Myers Squibb, Celltrion Pharm, Eli Lilly and Company, Pfizer, Roche, and UCB outside the submitted work. Dr Carmona reported receiving grants from AbbVie, Gebro Pharma, Grünenthal, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Aventis, and UCB outside the submitted work. Dr Mateus reported receiving grants from AbbVie, A. Menarini Diagnostics, Amgen, Eli Lilly and Company, Grünenthal, Medac Pharma, Merck Sharp & Dohme, Novartis, and Pfizer and personal fees from Boehringer Ingelheim outside the submitted work. Dr Cruz-Machado reported receiving grants from Merck Sharp & Dohme outside the submitted work. Dr Hasseli reported receiving grants from Justus Liebig University during the conduct of the study. Dr Wise reported receiving personal fees from Aurinia Pharmaceuticals outside the submitted work. Dr Duarte-García reported receiving grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation outside the submitted work. Dr Isnardi reported receiving grants from AbbVie, Laboratorio Elea Phoenix, and Pfizer during the conduct of the study and personal fees from Bristol Myers Squibb outside the submitted work. Dr Soriano reported receiving grants from Novartis, Pfizer, Roche, and UCB and personal fees from AbbVie, Amgen, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis, Pfizer, and Sandoz outside the submitted work. Dr Sparks reported receiving grants from the National Institutes of Health and the Rheumatology Research Foundation and personal fees from Bristol Myers Squibb, Gilead Sciences, Inova Diagnostics, Optum, and Pfizer outside the submitted work. Dr Patel reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Xavier reported receiving personal fees from AbbVie, Eli Lilly and Company, Novartis, Pfizer, and UCB outside the submitted work. Dr Kakehasi reported receiving grants from the National Council for Scientific and Technological Development during the conduct of the study; personal fees from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis, Pfizer, Sandoz, and UCB outside the submitted work. Dr Flipo reported receiving personal fees from AbbVie, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Pfizer outside the submitted work. Dr Claudepierre reported receiving personal fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos, Janssen Pharmaceuticals, Merck & Co, Novartis, Pfizer, Roche Chugai, and UCB outside the submitted work. Dr Goupille reported receiving personal fees from AbbVie, Biogen, Bristol Myers Squibb, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis, Pfizer, and UCB outside the submitted work. Dr Wallace reported receiving grants from Bristol Myers Squibb and Sanofi and personal fees from Medpace Holdings and Viela Bio outside the submitted work. Dr Bhana reported receiving personal fees from AbbVie, Amgen, Horizon Therapeutics, Novartis, and Pfizer outside the submitted work. Dr Grainger reported receiving personal fees from AbbVie, Cornerstone Pharmaceuticals, Janssen Pharmaceuticals, Novartis, and Pfizer and nonfinancial support from Pfizer outside the submitted work. Dr Hausmann reported receiving grants from the Childhood Arthritis and Rheumatology Research Alliance and the Rheumatology Research Foundation and personal fees from Biogen, Novartis, and Pfizer outside the submitted work. Dr Liew reported receiving grants from Pfizer outside the submitted work. Ms Sirotich reported receiving grants from the COVID-19 Global Rheumatology Alliance and serving as a board member of the Canadian Arthritis Patient Alliance outside the submitted work. Dr Robinson reported receiving grants from Janssen Pharmaceuticals and Novartis and personal fees from AbbVie, Atom Bioscience, BMC Pharma, Eli Lilly and Company, Gilead Sciences, Pfizer, Roche, and UCB outside the submitted work. Dr Machado reported receiving grants from Orphazyme and personal fees from AbbVie, Eli Lilly and Company, Galapagos, Novartis, Orphazyme, and UCB outside the submitted work. Dr Griffiths reported receiving grants from the National Institute for Health Research during the conduct of the study; grants from Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, and LEO Pharma; and personal fees from AbbVie, Almirall, Bristol Myers Squibb, Novartis, and UCB outside the submitted work. Dr Barker reported receiving personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Samsung Pharmaceutical, Sienna Biopharmaceuticals, Sun Pharmaceutical Industries, and UCB outside the submitted work. Dr Smith reported receiving grants from Guy’s and St Thomas’ Biomedical Research Centre and the Psoriasis Association during the conduct of the study and grants from the Horizon 2020 Initiative and the Medical Research Council outside the submitted work. Dr Yazdany reported receiving grants from the American College of Rheumatology, Gilead Sciences, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study; grants from AstraZeneca and Bristol Myers Squibb; and personal fees from Aurinia Pharmaceuticals, Eli Lilly and Company, and Pfizer outside the submitted work. Dr Kappelman reported receiving grants from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Pharm, Eli Lilly and Company, Genentech, Janssen Pharmaceuticals, Pfizer, and Takeda Pharmaceutical during the conduct of the study; personal fees from AbbVie, Eli Lilly and Company, Johnson & Johnson, Pfizer, and Takeda Pharmaceutical; and owning shares in Johnson & Johnson outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by funding to the COVID-19 Global Rheumatology Alliance from the American College of Rheumatology and the European League Against Rheumatism and funding to the Members of Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection from the Department of Health (via the National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, United Kingdom), the National Institute for Health Research Manchester Biomedical Research Centre, and the Psoriasis Association.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: Members of the 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) are listed in Supplement 2.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the American College of Rheumatology, the Department of Health and Social Care (United Kingdom), the European Alliance of Associations for Rheumatology, the National Health Service (United Kingdom), or the National Institute for Health Research (United Kingdom).

Additional Contributions: We acknowledge the members of 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) for their assistance with development and promotion of the registries.

References
1.
Stallmach  A , Kortgen  A , Gonnert  F , Coldewey  SM , Reuken  P , Bauer  M .  Infliximab against severe COVID-19–induced cytokine storm syndrome with organ failure—a cautionary case series.   Crit Care. 2020;24(1):444. doi:10.1186/s13054-020-03158-0 PubMedGoogle ScholarCrossref
2.
Centers for Disease Control and Prevention. People with certain medical conditions. Centers for Disease Control and Prevention; 2020. Updated August 20, 2021. Accessed January 7, 2020. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html
3.
Kuek  A , Hazleman  BL , Ostor  AJ .  Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution.   Postgrad Med J. 2007;83(978):251-260. doi:10.1136/pgmj.2006.052688 PubMedGoogle ScholarCrossref
4.
Robinson  PC , Liew  DFL , Liew  JW ,  et al.  The potential for repurposing anti-TNF as a therapy for the treatment of COVID-19.   Med (N Y). 2020;1(1):90-102.PubMedGoogle Scholar
5.
Brenner  EJ , Ungaro  RC , Gearry  RB ,  et al.  Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry.   Gastroenterology. 2020;159(2):481-491. doi:10.1053/j.gastro.2020.05.032 PubMedGoogle ScholarCrossref
6.
Gianfrancesco  M , Hyrich  KL , Al-Adely  S ,  et al; COVID-19 Global Rheumatology Alliance.  Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.   Ann Rheum Dis. 2020;79(7):859-866. doi:10.1136/annrheumdis-2020-217871 PubMedGoogle ScholarCrossref
7.
Mahil  SK , Dand  N , Mason  KJ ,  et al; PsoProtect Study Group.  Factors associated with adverse COVID-19 outcomes in patients with psoriasis—insights from a global registry-based study.   J Allergy Clin Immunol. 2021;147(1):60-71. doi:10.1016/j.jaci.2020.10.007 PubMedGoogle ScholarCrossref
8.
Robinson  PC , Yazdany  J .  The COVID-19 Global Rheumatology Alliance: collecting data in a pandemic.   Nat Rev Rheumatol. 2020;16(6):293-294. doi:10.1038/s41584-020-0418-0 PubMedGoogle ScholarCrossref
9.
Wallace  ZS , Bhana  S , Hausmann  JS ,  et al.  The rheumatology community responds to the COVID-19 pandemic: the establishment of the COVID-19 Global Rheumatology Alliance.   Rheumatology (Oxford). 2020;59(6):1204-1206. doi:10.1093/rheumatology/keaa191 PubMedGoogle ScholarCrossref
10.
Gianfrancesco  MA , Hyrich  KL , Gossec  L ,  et al; COVID-19 Global Rheumatology Alliance Steering Committee.  Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.   Lancet Rheumatol. 2020;2(5):e250-e253. doi:10.1016/S2665-9913(20)30095-3 PubMedGoogle ScholarCrossref
11.
Vittinghoff  E , Glidden DV, Shiboski SC, McCulloch CE.  Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. Springer; 2012. doi:10.1007/978-1-4614-1353-0
12.
Westreich  D , Edwards  JK , Lesko  CR , Stuart  E , Cole  SR .  Transportability of trial results using inverse odds of sampling weights.   Am J Epidemiol. 2017;186(8):1010-1014. doi:10.1093/aje/kwx164 PubMedGoogle ScholarCrossref
13.
Franklin  JM , Pawar  A , Martin  D ,  et al.  Nonrandomized real-world evidence to support regulatory decision making: process for a randomized trial replication project.   Clin Pharmacol Ther. 2020;107(4):817-826. doi:10.1002/cpt.1633 PubMedGoogle ScholarCrossref
14.
Austin  PC .  Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.   Stat Med. 2009;28(25):3083-3107. doi:10.1002/sim.3697 PubMedGoogle ScholarCrossref
15.
Del Valle  DM , Kim-Schulze  S , Huang  HH ,  et al.  An inflammatory cytokine signature predicts COVID-19 severity and survival.   Nat Med. 2020;26(10):1636-1643. doi:10.1038/s41591-020-1051-9 PubMedGoogle ScholarCrossref
16.
Dolinger  MT , Person  H , Smith  R ,  et al.  Pediatric Crohn disease and multisystem inflammatory syndrome in children (MIS-C) and COVID-19 treated with infliximab.   J Pediatr Gastroenterol Nutr. 2020;71(2):153-155. doi:10.1097/MPG.0000000000002809 PubMedGoogle ScholarCrossref
17.
Rodriguez-Lago  I , Ramirez de la Piscina  P , Elorza  A , Merino  O , Ortiz de Zarate  J , Cabriada  JL .  Characteristics and prognosis of patients with inflammatory bowel disease during the SARS-CoV-2 pandemic in the Basque Country (Spain).   Gastroenterology. 2020;159(2):781-783. doi:10.1053/j.gastro.2020.04.043 PubMedGoogle ScholarCrossref
18.
A phase 2 trial of infliximab in coronavirus disease 2019 (COVID-19). ClinicalTrials.gov identifier: NCT04425538. Updated February 18, 2021. Accessed January 7, 2020. https://clinicaltrials.gov/ct2/show/NCT04425538
19.
AVID-CC Trial Investigators. AVID-CC: adalimumab for coronavirus in community care. Websites for OCTRU Trials; 2020. Accessed January 7, 2020. https://avid-cc.octru.ox.ac.uk/
20.
Goodsall  TM , Costello  SP , Bryant  RV .  COVID-19 and implications for thiopurine use.   Med J Aust. 2020;212(10):490. doi:10.5694/mja2.50613 PubMedGoogle ScholarCrossref
21.
Kirchgesner  J , Lemaitre  M , Carrat  F , Zureik  M , Carbonnel  F , Dray-Spira  R .  Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases.   Gastroenterology. 2018;155(2):337-346. doi:10.1053/j.gastro.2018.04.012 PubMedGoogle ScholarCrossref
22.
Toruner  M , Loftus  EV  Jr , Harmsen  WS ,  et al.  Risk factors for opportunistic infections in patients with inflammatory bowel disease.   Gastroenterology. 2008;134(4):929-936. doi:10.1053/j.gastro.2008.01.012 PubMedGoogle ScholarCrossref
23.
Wisniewski  A , Kirchgesner  J , Seksik  P ,  et al; The Saint-Antoine IBD Network.  Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines.   United European Gastroenterol J. 2019;8(3):303-313. doi:10.1177/2050640619889763 PubMedGoogle ScholarCrossref
24.
Ungaro  RC , Brenner  EJ , Gearry  RB ,  et al.  Effect of IBD medications on COVID-19 outcomes: results from an international registry.   Gut. 2021;70(4):725-732. doi:10.1136/gutjnl-2020-322539 PubMedGoogle ScholarCrossref
25.
Frohman  EM , Villemarette-Pittman  NR , Cruz  RA ,  et al.  Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: an immune stabilization strategy for SARS-CoV-2 induced ‘PANIC’ attack.   J Neurol Sci. 2020;415:116935. doi:10.1016/j.jns.2020.116935 PubMedGoogle Scholar
26.
Safavi  F , Nath  A .  Silencing of immune activation with methotrexate in patients with COVID-19.   J Neurol Sci. 2020;415:116942. doi:10.1016/j.jns.2020.116942 PubMedGoogle Scholar
27.
Lichtenstein  GR , Loftus  EV , Isaacs  KL , Regueiro  MD , Gerson  LB , Sands  BE .  ACG clinical guideline: management of Crohn’s disease in adults.   Am J Gastroenterol. 2018;113(4):481-517. doi:10.1038/ajg.2018.27 PubMedGoogle ScholarCrossref
28.
Maini  RN , Breedveld  FC , Kalden  JR ,  et al.  Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.   Arthritis Rheum. 1998;41(9):1552-1563. doi:10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W PubMedGoogle ScholarCrossref
29.
Kalil  AC , Patterson  TF , Mehta  AK ,  et al; ACTT-2 Study Group Members.  Baricitinib plus remdesivir for hospitalized adults with Covid-19.   N Engl J Med. 2021;384(9):795-807. doi:10.1056/NEJMoa2031994 PubMedGoogle ScholarCrossref
30.
Kilian  A , Chock  YP , Huang  IJ ,  et al.  Acute respiratory viral adverse events during use of antirheumatic disease therapies: a scoping review.   Semin Arthritis Rheum. 2020;50(5):1191-1201. doi:10.1016/j.semarthrit.2020.07.007 PubMedGoogle ScholarCrossref
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