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.
- rheumatoid arthritis
- tumour necrosis factor inhibitors
Data availability statement
Data are available upon reasonable request. Applications to access the data should be made to the C19-GRA Steering Committee.
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JAS and ZSW are joint first authors.
Handling editor Josef S Smolen
Twitter @jeffsparks, @zach_wallace_md, @carmona_loreto, @saskiaamber, @gponsestel, @kmdsilvaMD, @rthritis, @Mota_licia_reum, @PhilippeDieude, @ElenaNikiUK, @mugartegil, @Akpabioakanimo, @hausmannmd, @rheum_cat, @emilysirotich, @philipcrobinson, @pedrommcmachado
JAS and ZSW contributed equally.
Correction notice This article has been corrected since it published Online First. Collaborator names have been updated.
Collaborators Brahim Dahou (Association Rhumatologues Algériens Privés (ARAP), Algeria), Rosana Quintana, Gimena Gómez, Karen Roberts, Roberto Miguel Baez, Vanessa Castro Coello, María J Haye Salinas, Federico Nicolas Maldonado, Alvaro Andres Reyes Torres, Gelsomina Alle, Romina Tanten, Hernán Maldonado Ficco, Romina Nieto, Carla Gobbi, Yohana Tissera, Cecilia Pisoni, Alba Paula, Juan Alejandro Albiero, Maria Marcela Schmid, Micaela Cosatti, Maria Julieta Gamba, Carlevaris Leandro, María Alejandra Cusa, Noelia German, Veronica Bellomio, Lorena Takashima, Mariana Pera, Karina Cogo, Maria Soledad Gálvez Elkin, María Alejandra Medina, Veronica Savio, Ivana Romina Rojas Tessel, Rodolfo Perez Alamino, Marina Laura Werner, Sofía Ornella, Luciana Casalla, Maria de la Vega, María Severina, Mercedes García, Luciana Gonzalez Lucero, Cecilia Romeo, Sebastián Moyano, Tatiana Barbich, Ana Bertoli, Andrea Baños, Sandra Petruzzelli, Carla Matellan, Silvana Conti, Ma Alicia Lazaro, Gustavo Fabián Rodriguez Gil, Fabian Risueño, Maria Isabel Quaglia, Julia Scafati, Natalia Lili Cuchiaro, Jonathan Eliseo Rebak, Susana Isabel Pineda, María Elena Calvo, Eugenia Picco, Josefina Gallino Yanzi, Pablo Maid, Debora Guaglianone, Julieta Silvana Morbiducci, Sabrina Porta, Natalia Herscovich, José Luis Velasco Zamora, Boris Kisluk, Maria Sol Castaños Menescardi, Rosana Gallo, María Victoria Martire, Carla Maldini, Cecilia Goizueta, Sabrina Solange de la vega Fernandez, Carolina Aeschlimann Argentina, Gisela Subils (Argentine Society of Rheumatology, Argentina), Eva Rath (Hanusch Krankenhaus, Vienna, Austria), Yves Piette (AZ Sint-Jan Brugge, Belgium), Mieke Devinck (AZ Sint-Lucas Brugge, Belgium), Bea Maeyaert (AZ Sint-Lucas Brugge, Hospital Universitário Pedro Ernesto Universidade do, Belgium), Francinne Machado Ribeiro (Estado do Rio de Janeiro, Brazil), Sandra Lucia Euzebio Ribeiro (Federal University of Amazonas, Universidade Federal De São Paulo Escola Paulista de, Brazil), Marcelo Pinheiro (Medicina e Escola Paulista de Enfermagem, Brazil), Sebastián Ibáñez (Clínica Alemana de Santiago, Chile), Anne-Marie Chassin-Trubert (Complejo Hospitalario San José, Chile), Lingli Dong (Tongji Hospital, China), Lui Cajas (Clinica Universitaria Colombia - Centro Medico Providencia Sanitas, Colombia), Marko Barešić (University Hospital Center Zagreb, Croatia), Branimir Anić (Div Clin Immunol Rheumatol; Dept Int Med, School of Med Zagreb, University Hospital Center Zagreb, Croatia), Melanie-Ivana Čulo (University Hospital Dubrava, Zagreb, Croatia), Tea Ahel Pavelić (Clinical Hospital Center Rijeka, Croatia), Kristina Kovačević (Stranski University hospital Osijek, Croatia), Boris Karanovic (UHC Zagreb, Croatia), Jiri Vencovsky (Institute of Rheumatology, Prague, Czechia), Marta Píchová (Medipont plus s.ro., České Budějovice, Czechia), Maria Filkova (Institute of Rheumatology, Prague, Czechia), Hesham Hamoud (Al Azhar University Hospitals, Egypt), Dimitrios Vassilopoulos (Hippokration General Hospital, Athens, Greece), Gabriela Maria Guzman Melgar (Hospital del Valle, Honduras, Honduras), Ho So (Chinese University of Hong Kong, Hong Kong), Márta Király (Petz Aladár University Teaching Hospital, Győr, Hungary), Mahdi Vojdanian (Iran Rheumatology Center, Iran), Alexandra Balbir-Gurman (Rambam Rheumatology Institute, Haifa, Israel), Fatemah Abutiban (Kuwait Rheumatology Association, Kuwait), Julija Zepa, Inita Bulina (Pauls Stradins Clinical University Hospital, Riga, Latvia), Loreta Bukauskiene (Klaipeda university hospital, Lithuania), Beatriz Elena Zazueta-Montiel (Centro Medico del Angel, Mexico), Angel Alejandro Castillo-Ortiz (Centro Medico Las Americas, Mexico), Erick Zamora-Tehozol (Centro Medico Pensiones, Mexico), David Vega-Morales (Hospital General de Zona #17, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico), Diana Cervántes Rosete, Eduardo Martín-Nares, Tatiana Sofia Rodriguez-Reyna (Salvador Zubirán, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico), Marina Rull Gabayet (Salvador Zubirán, Mexico), Deshiré Alpízar-Rodríguez (Mexican College of Rheumatology, Mexico), Fedra Irazoque (Private Practice, Mexico), Xochitl Jimenez (Centro Medico Naval, Mexico), Lenny Geurts-van Bon (Ziekenhuisgroep Twente, The Netherlands), Theo Zijlstra (Isala Hospital, Zwolle The Netherlands), Monique Hoekstra (Isala Hospital, Zwolle The Netherlands), Nasra Al-Adhoubi (Royal Hospital, Oman), Babur Salim (Fauji Foundation Hospital, Pakistan), Enrique Giraldo (Complejo Hospitalario, Panama), Ariel Salinas (Hospital Essalud Alberto Sabogal Sologuren, Universidad Científica del Sur-Hospital Guillermo, Peru), Manuel Ugarte-Gil (Almenara Irigoyen, Peru), Jarosław Nowakowski (University Hospital, Krakow, Poland), Samar Al-Emadi (Hamad Medical Corporation, Qatar), Richard Conway (St James' Hospital, Dublin, Republic of Ireland), Rachael Flood (Tallaght University Hospital, Republic of Ireland), Geraldine McCarthy (Mater Misericordiae University Hospital, Republic of Ireland), Ioana Felea, Ileana Filipescu, Simona Rednic (County Emergency Hospital, Cluj Napoca, Romania), Laura Groseanu (Sf Maria Clinical Hospital, Bucharest, Romania), Maria Magdelena (Tamas County Emergency Hospital, Cluj Napoca, Romania), Vanda, Mlynarikova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic), Martina Skamlova (FNSPFDR, Banská Bystrica, Slovak Republic), Martin Zlnay, Dagmar Mičeková (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic), Lubica Capova (University Hospital, Bratislava, Slovak Republic), Zelmira Macejova (University Hospital, Košice, Slovak Republic), Emőke Šteňová (University Hospital Bratislava, Slovak Republic), Helena Raffayova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic), Gabriela Belakova (Medman s.r.o., Martin, Slovak Republic), Eva Strakova (Faculty hospital Prešov, Slovak Republic), Marieta Senčarová (Louis Pasteur University Hospital, Košice, Slovak Republic), Soňa Žlnayová (Poliklinika MarMedico, s.r.o., Nové Mesto nad Váhom Slovak Republic súkromná reumatologická ambulancia, Vranov nad, Slovak Republic), Anna Sabová (Topľou, Slovak Republic), Daniela Spisakova (University Hospital od L. Pasteur Kosice, Slovak Republic), Mária Oetterová (Safarik University hospital, Kosice, Slovak Republic), Olga Lukacova (National Institute of Rheumatic Diseases, Piešťany, Slovak Republic), Martina Bakosova (UNB Nemocnica Stare Mesto, Bratislava, Slovak Republic), Alojzija Hocevar (UMC Ljubljana, Slovenia), Natalia de la Torre-Rubio (Hospital Universitario Puerta de Hierro Majadahonda, Spain), Juan José Alegre Sancho (Hospital Universitari Dr Peset, Valencia, Spain), Montserrat Corteguera Coro (Complejo Asistencial Avila, Spain), Juan Carlos Cobeta Garcia (Hospital Ernest Lluch, Calatayud, Spain), Maria Carmen Torres Martin (Hospital Nuestra Senora Sonsoles, Avila, Spain), Jose Campos (Hospital Universitario Puerta de Hierro, Spain), Jose A Gomez Puerta (Hospital Clinic Barcelona, Spain), Gozd Kubra Yardımcı, Servet Akar (Hacettepe University Faculty of Medicine, Ankara, Izmir Katip Celebi University Atatürk Training and Research Hospital, Izmir, Turkey), Ozan Cemal Icacan (Bakırköy Dr. Sadi Konuk Research And Training Hospital, Istanbul, Turkey), Selda ÇELİK (Bakirkoy Dr Sadi Konuk Educational And Research Hospital, Rheumatology Department, Turkey), Viktoriia Vasylets (Multifield Medical Centre, Odessa, Ukraine), Su-Ann Yeoh (University College London Hospital, London, UK), Claire Vandevelde (Leeds Teaching Hospitals NHS Trust, UK), Sasha Dunt (Countess of Chester NHS Foundation Trust, UK), Jane Leeder (Norfolk & Norwich University Hospital, UK), Elizabeth Macphie (Lancashire and South Cumbria NHS Foundation Trust, UK), Rosaria Salerno (King's College Hospital, UK), Christine Graver (Hampshire Hospitals NHS Trust, UK), Katie Williams (York District Hospital, UK), Sheila O'Reilly (Royal Derby Hospital, UK), Kirsty Devine (York/Scarborough Hospitals, UK), Jennifer Tyler (Royal United Hospital, Bath, UK), Elizabeth Warner (Lister Hospital, UK), James Pilcher (University Hospital Lewisham, UK), Samir Patel (Queen Elizabeth hospital Woolwich, UK), Elena Nikiphorou (King's College Hospital, UK), Laura Chadwick (St Helens & Knowsley NHS Foundation Trust, UK), Caroline Mulvaney Jones (Llandudno Hospital, UK), Beverley Harrison (Salford Royal NHS FT, UK), Lucy Thornton (Bradford Royal Infirmary, UK), Diana O'Kane (RNHRD at Royal United Hospital Bath, UK), Lucia Fusi (King's College Hospital, UK), Audrey Low (Salford Royal NHS FT, UK), Sarah Horton (Minerva Health Centre, UK), Shraddha Jatwani (Albert Einstein Medical Center, PA, USA), Sara Baig, Hammad Bajwa, Vernon Berglund, Angela Dahle, Walter Dorman, Jody Hargrove, Maren Hilton, Nicholas Lebedoff, Susan Leonard, Jennifer Morgan, Emily Pfeifer, Archibald Skemp, Jeffrey Wilson, Anne Wolff (Arthritis and Rheumatology Consultants, PA, USA), Eduardo Cepeda (Austin Diagnostic Clinic, USA), Derrick Todd (Brigham and Women's Hospital, USA), Denise Hare (Capital Health Rheumatology, USA), Cassandra Calabrese (Cleveland Clinic, USA), Christopher Adams (East Alabama Medical Center, USA), Arezou Khosroshahi (Emory University, USA), Adam Kilian (George Washington University, USA), Douglas White, Melanie Winter (Gundersen Health System, USA), Theodore Fields (Hospital for Special Surgery, USA), Caroline Siegel (Hospital for Special Surgery, USA), Nicole Daver (Institute of Rheumatic and Autoimmune Diseases, USA), Melissa Harvey (Institute of Rheumatic and Autoimmune Diseases, USA), Neil Kramer (Institute of Rheumatic and Autoimmune Diseases, USA), Concetta Lamore (Institute of Rheumatic and Autoimmune Diseases, USA), Suneya Hogarty (Integrative Arthritis and Pain Consultants, USA), Karen Yeter (Kaiser Permanente, USA), Leanna Wise (Los Angeles County + USC Medical Center, USA), Faizah Siddique (Loyola University Medical Center, USA), Byung Ban (Medstar Georgetown University Hospital, USA), Tamar Tanner (Montefiore Medical Center, USA), Eric Ruderman (Northwestern Memorial, USA), William Davis, Robert Quinet, Evangeline Scopelitis, Karen Toribio Toribio, Tameka Webb-Detiege, Jerald Zakem (Ochsner Medical Center Rheumatology Department, USA), Khurram Abbass, Gilbert Kepecs (Private Practice, USA), Lilliam Miranda (Rheumatology Center INC, USA), Michael Guma, Ammar Haikal, Sushama Mody (Riverside Medical Group, USA), Daric Mueller (Shores Rheumatology PC, USA), Arundathi Jayatilleke (Temple University Hospital, USA), JoAnn Zell (University of Colorado, USA), Alison Bays (University of Washington, Seattle, USA), Kathryn Dao, Ezzati Fatemeh (UT Southwestern Medical Center, USA), Deborah Parks (Washington University Div of Rheumatology, USA), David Karp, Guillermo Quiceno (UT Southwestern Medical Center, USA).
Contributors JAS, ZSW, AS, MG and JY had access to the study data, developed the figures and tables, and vouch for the data and analyses. AS and MG performed the statistical analyses and contributed to data quality control, data analysis and interpretation of data. JAS, ZSW, AMS, MG, ZI, KLH, AS, LG, LC, EFM, SL-T, LT, SR, PK, GS, LJ, SAE, LW, ELG, AD-G, MOV-A, GJP-E, CAI, GAB, TY-TH, KMD’S, NJP, PD, EN, VLK, NS, MFU-G, BW, AA, RT, SB, WC, RG, JH, JL, ES, PS, PCR, PMM and JY contributed to data collection, data analysis and interpretation of data. JAS, ZSW and JY directed the work, designed the data collection methods, contributed to data collection, data analysis and interpretation of data, and had final responsibility for the decision to submit for publication. All authors contributed intellectual content during the drafting and revision of the work and approved the final version to be published.
Funding The study received support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR).
Disclaimer The views expressed here are those of the authors and the participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology (ACR), the European Alliance of Associations for Rheumatology (EULAR), the (UK) National Health Service (NHS), the National Institute for Health Research (NIHR) or the (UK) Department of Health, or any other organisation.
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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