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. 2021 Sep;80(9):1137-1146.
doi: 10.1136/annrheumdis-2021-220418. Epub 2021 May 28.

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 physician registry

Jeffrey A Sparks #  1   2 , Zachary S Wallace #  3   4 , Andrea M Seet  5 , Milena A Gianfrancesco  5 , Zara Izadi  6 , Kimme L Hyrich  7   8 , Anja Strangfeld  9 , Laure Gossec  10   11 , Loreto Carmona  12 , Elsa F Mateus  13   14 , Saskia Lawson-Tovey  15   16 , Laura Trupin  5 , Stephanie Rush  5 , Patricia Katz  5 , Gabriela Schmajuk  5   17 , Lindsay Jacobsohn  5 , Leanna Wise  18 , Emily L Gilbert  19 , Ali Duarte-García  20 , Maria O Valenzuela-Almada  21 , Guillermo J Pons-Estel  22 , Carolina A Isnardi  22 , Guillermo A Berbotto  23 , Tiffany Y-T Hsu  24 , Kristin M D'Silva  4 , Naomi J Patel  4 , Lianne Kearsley-Fleet  7 , Martin Schäfer  9 , Sandra Lúcia Euzébio Ribeiro  25 , Samar Al Emadi  26 , Liselotte Tidblad  27 , Carlo Alberto Scirè  28 , Bernd Raffeiner  29 , Thierry Thomas  30 , René-Marc Flipo  31 , Jérôme Avouac  32 , Raphaèle Seror  33 , Miguel Bernardes  34   35 , Maria Margarida Cunha  36 , Rebecca Hasseli  37 , Hendrik Schulze-Koops  38 , Ulf Müller-Ladner  37 , Christof Specker  39 , Viviane Angelina de Souza  40 , Licia Maria Henrique da Mota  41 , Ana Paula Monteiro Gomides  42 , Philippe Dieudé  43 , Elena Nikiphorou  44 , Vanessa L Kronzer  45 , Namrata Singh  46 , Manuel F Ugarte-Gil  47   48 , Beth Wallace  49   50 , Akpabio Akpabio  51 , Ranjeny Thomas  52 , Suleman Bhana  53 , Wendy Costello  54 , Rebecca Grainger  55 , Jonathan S Hausmann  56   57 , Jean W Liew  58 , Emily Sirotich  59   60 , Paul Sufka  61 , Philip C Robinson  62   63 , Pedro M Machado  64   65 , Jinoos Yazdany  5 ; COVID-19 Global Rheumatology Alliance
Collaborators, Affiliations

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 physician registry

Jeffrey A Sparks et al. Ann Rheum Dis. 2021 Sep.

Abstract

Objective: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).

Methods: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.

Results: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.

Conclusions: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Keywords: Covid-19; abatacept; rheumatoid arthritis; rituximab; tumour necrosis factor inhibitors.

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Conflict of interest statement

Competing interests: JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253 and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R Bruce and Joan M Mickey Research Scholar Fund. JAS has received research support from Amgen and Bristol-Myers Squibb and performed consultancy for Bristol-Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. ZSW reports grant support from Bristol-Myers Squibb and Principia/Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. MG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534; JY). KLH reports she has received speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this study. KLH is also supported by the NIHR Manchester Biomedical Research Centre. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories such as, among other institutions, AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz and Sanofi; consulting fees from AbbVie, Amgen, BMS, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi Aventis and UCB, all unrelated to this study. EFM reports that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharma Kern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. AS reports 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, and personal fees from lectures for AbbVie, MSD, Roche, BMS and Pfizer, outside the submitted work. AD-G has no disclosures relevant to this study. His work is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. KMD is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258) and the Rheumatology Research Foundation. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). PD has received research support from Bristol-Myers Squibb, Chugai and Pfizer, and performed consultancy for Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche and Janssen, unrelated to this work. NS is supported by the RRF Investigator Award and the American Heart Association. MFU-G reports grant support from Janssen and Pfizer. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon, Novartis and Pfizer (all <$10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones, and travel assistance from Pfizer (all <$10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<$10 000). JL has received research funding from Pfizer, outside the submitted work. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient-run, volunteer-based organisation whose activities are largely supported by independent grants from pharmaceutical companies. PS reports no competing interests related to this work. He reports honorarium for doing social media for American College of Rheumatology journals (<$10 000). PMM has 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). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work he reports personal consulting and/or speaking fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and travel assistance from Roche (all <$10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health, Centers for Disease Control, and the Agency for Healthcare Research and Quality. She has performed consulting for Eli Lilly and AstraZeneca, unrelated to this project.

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