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OP0006 ASSOCIATIONS OF BASELINE USE OF BIOLOGIC OR TARGETED SYNTHETIC DMARDS WITH COVID-19 SEVERITY IN RHEUMATOID ARTHRITIS: RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE
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  1. J. Sparks1,2,
  2. Z. Wallace2,3,
  3. A. Seet4,
  4. M. Gianfrancesco4,
  5. Z. Izadi4,5,
  6. K. Hyrich6,7,
  7. A. Strangfeld8,
  8. L. Gossec9,10,
  9. L. Carmona11,
  10. E. Mateus12,13,
  11. S. Lawson-Tovey7,14,
  12. L. Trupin4,
  13. S. Rush4,
  14. G. Schmajuk4,15,
  15. P. Katz4,
  16. L. Jacobsohn4,
  17. S. Al Emadi16,
  18. L. Wise17,
  19. E. Gilbert18,
  20. A. Duarte-Garcia19,
  21. M. Valenzuela-Almada20,
  22. T. Hsu1,
  23. K. D’silva2,3,
  24. N. Serling-Boyd2,3,
  25. P. Dieudé21,
  26. E. Nikiphorou22,
  27. V. Kronzer18,
  28. N. Singh23,
  29. M. F. Ugarte-Gil24,
  30. B. Wallace25,26,
  31. A. Akpabio27,
  32. R. Thomas28,
  33. S. Bhana29,
  34. W. Costello30,
  35. R. Grainger31,
  36. J. Hausmann2,32,33,
  37. J. Liew34,
  38. E. Sirotich35,36,
  39. P. Sufka37,
  40. P. Robinson38,39,
  41. P. Machado40,41,42,
  42. J. Yazdany4
  43. on behalf of COVID-19 Global Rheumatology Alliance
  1. 1Brigham And Women’s Hospital, Division of Rheumatology, Inflammation, and Immunity, Boston, United States of America
  2. 2Harvard Medical School, Division of Rheumatology, Inflammation, and Immunity, Boston, United States of America
  3. 3Massachusetts General Hospital, Division of Rheumatology, Allergy, and Immunology, Boston, United States of America
  4. 4University of California, San Francisco, Division of Rheumatology, San Francisco, United States of America
  5. 5University of California, San Francisco, Department of Epidemiology and Biostatistics, San Francisco, United States of America
  6. 6The University of Manchester, Centre for Epidemiology Versus Arthritis, Manchester, United Kingdom
  7. 7Manchester University NHS FT, National Institute of Health Research Manchester Biomedical Research Centre, Manchester, United Kingdom
  8. 8Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, German Rheumatism Research Center, Berlin, Germany
  9. 9Institute Pierre Louis Epidemiology And Public Health, INSERM, Paris, France
  10. 10University Hospitals Pitié Salpêtrière - Charles Foix, Rheumatology Department, Paris, France
  11. 11Instituto de Salud Musculoesquelética (InMusc), Rheumatology Department, Madrid, Spain
  12. 12Portuguese League Against Rheumatic Diseases, Rheumatology Department, Lisbon, Portugal
  13. 13European League Against Rheumatism (EULAR) Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Department of Rheumatology, Kilchberg, Switzerland
  14. 14The University of Manchester, Centre for Genetics and Genomics Versus Arthritis, Manchester, United Kingdom
  15. 15San Francisco VA Medical Center, Division of Rheumatology, San Francisco, United States of America
  16. 16Hamad Medical Corporation, Rheumatology Department, Doha, Qatar
  17. 17University of Southern California, Division of Rheumatology, Los Angeles, United States of America
  18. 18Mayo Clinic, Division of Rheumatology, Rochester, United States of America
  19. 19Mayo Clinic, Division of Rheumatology and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, United States of America
  20. 18Mayo Clinic, Division of Rheumatology, Rochester, United States of America
  21. 21Bichat-Claude Bernard Hospital, Rheumatology Department, Paris, France
  22. 22King’s College London, Centre for Rheumatic Diseases, London, United Kingdom
  23. 23University of Washington, Division of Rheumatology, Seattle, United States of America
  24. 24Scientific University of the South, Rheumatology Department, Lima, Peru
  25. 25University of Michigan, Department of Internal Medicine/Rheumatology, Ann Arbor, United States of America
  26. 26VA Ann Arbor Healthcare System, Center for Clinical Management Research, Ann Arbor, United States of America
  27. 27Royal Hallamshire Hospital, Rheumatology Department, Sheffield, United Kingdom
  28. 28University of Queensland, UQ Diamantina Institute, Queensland, Australia
  29. 29Crystal Run Health, Rheumatology Department, Middletown, United States of America
  30. 30Irish Children’s Arthritis Network, Arthritis Department, Tipperary, Ireland
  31. 31University of Otago, Rheumatology Department, Dunedin, New Zealand
  32. 32Boston Children’s Hospital, Program in Rheumatology, Boston, United States of America
  33. 33Beth Israel Deaconess Medical Center (BIDMC), Division of Rheumatology and Clinical Immunology, Boston, United States of America
  34. 34Boston University School of Medicine, Section of Rheumatology, Boston, United States of America
  35. 35McMaster University, Department of Health Research Methods, Evidence, and Impact, Hamilton, Canada
  36. 36Canadian Arthritis Patient Alliance, Arthritis Department, Toronto, Canada
  37. 37Healthpartners, Rheumatology Department, St Paul, United States of America
  38. 38University of Queensland, Faculty of Medicine, Brisbane, Australia
  39. 39Metro North Hospital and Health Service, Faculty of Medicine, Queensland, Australia
  40. 40University College London, Centre for Rheumatology & Department of Neuromuscular Diseases, London, United Kingdom
  41. 41University College London Hospitals National Health Service (NHS) Trust, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, London, United Kingdom
  42. 42Northwick Park Hospital, Department of Rheumatology, London, United Kingdom

Abstract

Background: Targeted DMARDs may dampen the inflammatory response in COVID-19, perhaps leading to a less severe clinical course. However, some DMARD targets may impair viral immune defenses. Due to sample size limitations, previous studies of DMARD use and COVID-19 outcomes have combined several heterogeneous rheumatic diseases and medications, investigating a single outcome (e.g., hospitalization).

Objectives: To investigate the associations of baseline use of biologic or targeted synthetic (b/ts) DMARDs with a range of poor COVID-19 outcomes in rheumatoid arthritis (RA).

Methods: We analyzed voluntarily reported cases of COVID-19 in patients with rheumatic diseases in the COVID-19 Global Rheumatology Alliance physician registry (March 12, 2020 - January 6, 2021). We investigated RA treated with b/tsDMARD at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAK), interleukin-6 inhibitors (IL6i), or tumor necrosis factor inhibitors (TNFi). The outcome was an ordinal scale (1-4) for COVID-19 severity: 1) no hospitalization, 2) hospitalization without oxygen need, 3) hospitalization with any oxygen need or ventilation, or 4) death. Baseline covariates including age, sex, smoking, obesity, comorbidities (e.g., cardiovascular disease, cancer, interstitial lung disease [ILD]), concomitant non-biologic DMARD use, glucocorticoid use/dose, RA disease activity, country, and calendar time were used to estimate propensity scores (PS) for b/tsDMARD. The primary analysis used PS matching to compare each drug class to TNFi. Ordinal logistic regression estimated ORs for the COVID-19 severity outcome. In a sensitivity analysis, we used traditional multivariable ordinal logistic regression adjusting for covariates without matching.

Results: Of the 1,673 patients with RA on b/tsDMARDs at the onset of COVID-19, (mean age 56.7 years, 79.6% female) there were n=154 on ABA, n=224 on RTX, n=306 on JAK, n=180 on IL6i, and n=809 on TNFi. Overall, 498 (34.3%) were hospitalized and 112 (6.7%) died. Among all patients, 353 (25.3%) were ever smokers, 197 (11.8%) were obese, 462 (27.6%) were on glucocorticoids, 1,002 (59.8%) were on concomitant DMARDs, and 299 (21.7%) had moderate/high RA disease activity. RTX users were more likely than TNFi users to have ILD (11.6% vs. 1.7%) and history of cancer (7.1% vs. 2.0%); JAK users were more likely than TNFi users to be obese (17.3% vs. 9.0%). After propensity score matching, RTX was strongly associated with greater odds of having a worse outcome compared to TNFi (OR 3.80, 95% CI 2.47, 5.85; Figure). Among RTX users, 42 (18.8%) died compared to 27 (3.3%) of TNFi users (Table). JAK use was also associated with greater odds of having a worse COVID-19 severity (OR 1.52, 95%CI 1.02, 2.28). ABA or IL6i use were not associated with COVID-19 severity compared to TNFi. Results were similar in the sensitivity analysis and after excluding cancer or ILD.

Table 1.

Frequencies for the ordinal COVID-19 severity outcome for patients with RA on biologic or targeted synthetic DMARDs (n=1673).

Conclusion: In this large global registry of patients with RA and COVID-19, baseline use of RTX or JAK was associated with worse severity of COVID-19 compared to TNFi use. The very elevated odds for poor COVID-19 outcomes in RTX users highlights the urgent need for risk-mitigation strategies, such as the optimal timing of vaccination. The novel association of JAK with poor COVID-19 outcomes requires replication.

Acknowledgements: The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR, the UK National Health Service, the National Institute for Health Research, the UK Department of Health, or any other organization.

Disclosure of Interests: Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum, unrelated to this work, Grant/research support from: Amgen and Bristol-Myers Squibb, unrelated to this work, Zachary Wallace Consultant of: Viela Bio and MedPace, outside the submitted work., Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Andrea Seet: None declared, Milena Gianfrancesco: None declared, Zara Izadi: None declared, Kimme Hyrich Speakers bureau: Abbvie unrelated to this study, Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this study, Anja Strangfeld Paid instructor for: AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work, Grant/research support from: grants from a consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register, outside the submitted work, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, unrelated to this study, Grant/research support from: Lilly, Mylan, Pfizer, all unrelated to this study, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer, outside the submitted work, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Leanna Wise: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Manuel F. Ugarte-Gil Grant/research support from: Janssen and Pfizer, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all <$10,000) unrelated to this work, Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones, Jonathan Hausmann Consultant of: Novartis, Sobi, Biogen, all unrelated to this work (<$10,000), Jean Liew Grant/research support from: Yes, I have received research funding from Pfizer outside the submitted work., Emily Sirotich Grant/research support from: Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer based organization whose activities are largely supported by independent grants from pharmaceutical companies, Paul Sufka: None declared, Philip Robinson Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Pedro Machado Speakers bureau: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Consultant of: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Jinoos Yazdany Consultant of: Eli Lilly and AstraZeneca unrelated to this project

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