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

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). COVID-19 outcomes by severity scale (n,% ) ABA n=154 RTX n=224 JAK n=306 IL6i n=180 TNFi n=809 1)Not hospitalized 113 (73.3%) 121 (54.0%) 220 (71.9%) 150 (83.3%) 666 (82.3%) 2)Hospitalization without oxygenation 10 (6.5%) 14 (6.2%) 11 (3.6%) 9 (5.0%) 53 (6.5%) 3)Hospitalization with any oxygenation or ventilation 16 (10.4%) 47 (21.0%) 52 (17.0%) 16 (8.9%) 63 (7.8%) 4)Death 15 (9.7%) 42 (18.8%) 23 (7.5%) 5 (2.8%) 27 (3.3%) 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 Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 2Session: Opening Plenary Abstract session (Oral Presentations)