Letters Ann Rheum Dis: first published as 10.1136/annrheumdis-2020-217948 on 5 June 2020. Downloaded from http://ard.bmj.com/ on June 23, 2020 by guest. Protected by copyright. Clinical features and outcomes of COVID-19 in patients with rheumatic diseases treated with ­ biological and synthetic targeted therapies From the beginning of the COVID-19 pandemic, more than 4.7 million cases have been detected in the world, Spain being one of the countries hardest hit by the SARS-­CoV-2.1 The role of the immune system and immunomodulatory therapies in the evolution of this infection is still controversial.2 The study of patients with rheumatic and musculoskeletal diseases (RMDs) such as rheumatoid arthritis (RA), spondyloarthropathies (SpA) or systemic lupus erythematosus, treated with immunomodulatory ­ therapies is essential to understand the prognosis of COVID-19 in this specific population and to the management of these patients. BIOBADASER is a multicentre prospective observational registry ​ ​ ​ ​ ​ promoted by the Spanish Society of Rheumatology (SER) and supported by the Spanish Agency of Drugs and Medical Devices. It is aimed at assessing safety in patients with RMDs starting treat- ment with any biological (bDMARD) or targeted synthetic disease-­ modifying antirheumatic drug (tsDMARD). More than 6600 patients are prospectively followed up in BIOBADASER 3.0. This report describes the clinical characteristics and outcomes of patients with COVID-19 in BIOBADASER. We have identified 41 patients with RMDs treated with bDMARD and tsDMARD diagnosed of COVID-19 at 15 hospitals in the registry. Thirty-­one patients were diagnosed because positive PCR test for SARS-­CoV-2, and 10 patients because a highly compatible clinical picture and close contact with confirmed positive cases. Table 1 shows baseline characteristics of the patients. Twenty-­ five (61.0%) patients were female and 16 (39,0%) male, with a mean age of 59.4 years. They had long-­standing (12.8 years) refractory (three previous bDMARD/ tsDMARDs) diseases with 5.7 years of bDMARD/tsDMARD therapy duration. Twenty-­ one patients (51.2%) had RA. Comorbidities included hypertension (36.6%), past or current smoker (36.8%), diabetes (9.8%) and high body mass index (BMI) (27.7 (5.6) kg/m2— mean (SD)). Eighteen patients (43.9%) were using TNF inhibitors, seven JAK inhibitors (17.1%, 9.8% baricitinib and 7.3% tofacitinib) and five (12.2%) IL-6 inhibitors. Seventeen (41.5%) patients were using methotrexate and four (9,8%) hydroxychloroquine. Three patients died (7.3%); a 63-­year-­old RA male on anak- inra—plus prednisone 5 mg/day—(comorbidities: smoker, BMI 34.6); a 56-­year-­old SpA female on secukinumab—no glucocor- ticoids—(past smoker, BMI 28.4) and a 91-­year-­old vasculitis female on rituximab—plus prednisone 5 mg/day—(hyperten- sion). Hospitalisation was required in 28 patients (68.3%) and intensive care unit (ICU) admission in 6. Thirty-­five (85.4%) patients are fully recovered at the moment of this analysis, and three patients are still hospitalised, none in ICU. ​ ​ ​ ​ ​ ​ Data on COVID-19 in patients with RMDs is still scarce.3–6 Because of the rapid evolution of the pandemic, it is important to accrue information on the clinical course of rheumatic patients on bDMARD/tsDMARDs developing COVID-19. The . reduced number of patients in our study limits the possibility of drawing solid conclusions. However, these findings point in the direction that COVID-19 course and mortality in patients 988 Ann Rheum Dis July 2020 Vol 79 No 7 Letters Ann Rheum Dis: first published as 10.1136/annrheumdis-2020-217948 on 5 June 2020. Downloaded from http://ard.bmj.com/ on June 23, 2020 by guest. Protected by copyright. Table 1 Clinical features and treatments in patients with rheumatic diseases on targeted therapies with the diagnosis of COVID-19 Variable RA SpA Other rheumatic diseases Total N 21 12 8 41 Age at COVID-19 onset, years (SD) 61.3 (13.9) 57.1 (11.5) 57.1 (23.9) 59.4 (15.6) Sex, female, n (%) 14 (66.6) 5 (41.7) 6 (75.0) 25 (61.0) Disease duration (time since rheumatic diagnosis to COVID-19), years (SD) 12.0 (8.3) 15.0 (14.2) 11.4 (7.9) 12.8 (9.8) Time with bDMARDs/tsDMARDs (time since beginning of treatment to COVID-19), years (SD) 5.8 (5.2) 5.3 (5.8) 5.7 (9.6) 5.7 (5.7) Comorbidities and risk factors Charlson index, mean (SD) 2.5 (1.6) 2.3 (1.7) 3.4 (3.1) 2.6 (2.0) BMI, mean (SD) 27.9 (5.1) 29.4 (4.7) 25.2 (7.5) 27.7 (5.6) Hypertension, n (%) 6 (28.6) 5 (41.7) 4 (50.0) 15 (36.6) Smoking status, n (%)  Never smoker 14 (66.7) 8 (66.7) 5 (62.5) 27 (65.8)  Current smoker 2 (9.5) 0 (0.0) 2 (25.0) 4 (9.8)  Former smoker 5 (23.8) 4 (33.3) 1 (12.5) 10 (24.4) COVID-19 diagnosis, evolution and outcome COVID-19 diagnosis, n (%)  Confirmed cases (positive PCR test) 16 (76.2) 8 (66.7) 7 (87.5) 31 (75.6)  Suspicious cases (highly compatible clinical picture) 5 (23.8) 4 (33.3) 1 (12.5) 10 (24.4)  COVID-19 outcome  Recovered without sequelae 18 (85.7) 11 (91.7) 6 (75.0) 35 (85.4)  Not yet recovered 2 (9.5) 0 (0.0) 1 (12.5) 3 (7.3)  Death 1 (4.8) 1 (8.3) 1 (12.5) 3 (7.3)  Hospitalisation, n (%) 16 (76.2) 8 (66.7) 4 (50.0) 28 (68.3)  Intensive care unit, n (%) 4 (19.0) 2 (16.7) 0 (0.0) 6 (14.6) Rheumatic disease: treatment and clinical features Last DAS-28 available (previous to COVID-19), mean (SD) 3.9 (1.4) 3.3 (1.3) – 3.6 (1.4) bDMARD/tsDMARDs previous to COVID-19), n (%)  TNF inhibitors 7 (33.3) 7 (58.3) 4 (50.0) 18 (43.9)  Anti-­IL6 monoclonal antibodies 3 (14.3) 0 (0.0) 2 (25.0) 5 (12.2)  Anti-­CD20 monoclonal antibodies 2 (9.5) 0 (0.0) 1 (12.5) 3 (7.3)  Anti-­IL1 monoclonal antibodies 1 (4.8) 0 (0.0) 0 (0.0) 1 (2.4)  Anti-­IL17A monoclonal antibodies 0 (0.0) 5 (41.7) 0 (0.0) 5 (12.2)  Abatacept 1 (4.8) 0 (0.0) 1 (12.5) 2 (4.9)  JAK inhibitors 7 (33.3) 0 (0.0) 0 (0.0) 7 (17.1)  Baricitinib 4 (9.0) 0 (0.0) 0 (0.0) 4 (9.8)  Tofacitinib 3 (14.3) 0 (0.0) 0 (0.0) 3 (7.3) Number of previous bDMARD/tsDMARDs, mean (SD) 4.2 (2.9) 2.0 (1.0) 1.6 (0.7) 3.0 (2.4) Use of concomitant csDMARDS  Methotrexate 11 (52.4) 4 (33.3) 2 (25.0) 17 (41.5)  Hydroxychloroquine 2 (9.5) 0 (0.0) 2 (25.0) 4 (9.8)  Others 0 (0.0) 2 (16.7) 0 (0.0) 2 (4.9)  Monotherapy 12 (57.1) 6 (50.0) 4 (50.0) 22 (53.7)  Use of glucocorticoids, n (%) 13 (61.9) 2 (16.7) 5 (62.5) 20 (83.3) Dose of glucocorticoids (before COVID-19), mg, mean (SD) 5.5 (3.3) 7.5 (2.1) 6 (2.2) 5.8 (2.9) Concomitant use of NSAIDs, n (%) 7 (33.3) 3 (25.0) 0 (0.0) 10 (24.4) bDMARDs, biological disease-­modifying antirheumatic drugs; BMI, body mass index; n, number of patients; NSAIDs, non-­steroidal anti-­inflammatory drugs; RA, rheumatoid arthritis; SpA, spondyloarthropathies; tsDMARDs, targeted synthetic disease-­modifying antirheumatic drugs. with RMDs treated with b/tsDMARD do not differ from the Carlos Sanchez-­Piedra,1 Cesar Diaz-­Torne ‍ ‍,2 Javier Manero,3 general population (12.0% mortality rate and hospitalisation José M Pego-­Reigosa,4 Íñigo Rúa-­Figueroa ‍ ‍,5 rate 53.6% by COVID-19 in Spain1). Of interest, these high Miguel A Gonzalez-­Gay ‍ ‍,6 Juan Gomez-­Reino,7 Jose M Alvaro-­Gracia ‍ ‍,8 On behalf of the BIOBADASER study group mortality and hospitalisation rates are likely due to a diag- 1 nostic bias with PCR testing reserved for the most symptomatic Research Unit, Sociedad Española de Reumatologia, Madrid, Madrid, Spain 2 Rheumatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain patients, as suggested by a recent (unpublished) report by the 3 Rheumatology, Hospital Universitario Miguel Servet, Zaragoza, Aragón, Spain Spanish Ministry of Health showing a prevalence of IgG sero- 4 Rheumatology, Complejo Hospitalario de Vigo Hospital Xeral, Vigo, Galicia, Spain conversion to SARS-­Cov-2 of 5% in Spain. That is 10 times 5 Rheumatology, Hospital Universitario Insulsar Gran Canaria Doctor Negrin, Las greater than the PCR confirmed cases (1). The present data, in Palmas de Gran Canaria, Spain 6 addition to previous publications, is crucial to clarify the risks of Rheumatology, Hospital Universitario Marqués de Valdecilla Servicio de Medicina patients with rheumatic diseases and their immunosuppressive Interna, Santander, Cantabria, Spain 7 Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de medications. Doubtlessness, additional studies are still needed. Compostela, Galicia, Spain To this end, the SER is prospectively collecting information on 8 Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain COVID-19 in three registries (BIOBADASER, RELESSER and Correspondence to Dr Jose M Alvaro-­Gracia, Rheumatology, Hospital General CARMA) in more than 9000 patients with rheumatic diseases. Universitario Gregorio Marañón, 28007 Madrid, Spain; ​jalvarogracia@​gmail.​com Ann Rheum Dis July 2020 Vol 79 No 7 989 Letters Ann Rheum Dis: first published as 10.1136/annrheumdis-2020-217948 on 5 June 2020. Downloaded from http://ard.bmj.com/ on June 23, 2020 by guest. Protected by copyright. Handling editor Josef S Smolen appropriate credit is given, any changes made indicated, and the use is non-­ commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. Twitter Cesar Diaz-­Torne @cesardiaztorne © Author(s) (or their employer(s)) 2020. Re-­use permitted under CC BY-­NC. No Collaborators BIOBADASER study group: Dra. Maria Colazo (Hospital de commercial re-­use. See rights and permissions. Published by BMJ. Burgos), Dra Cristina Bohórquez (Hospital Universitario Príncipe de Asturias), Dr Javier del Pino (Hospital Universitario de Salamanca), Dra Paloma Vela-­ Casasempere (Hospital General Universitario de Alicante), Dra Sagrario Bustabad (Hospital de Canarias), Dr Manuel Pombo-­Suarez (Hospital Universitario de Santiago), Dr José Campos (Hospital Universitario Puerta de Hierro), Dra Raquel To cite Sanchez-­Piedra C, Diaz-­Torne C, Manero J, et al. Ann Rheum Dis Martín-­Domenech (Hospital General Universitario de Elda), Dra Cristina Campos-­ 2020;79:988–990. Fernandez (Hospital General Universitario de Valencia), Dra Rosa Roselló (Hospital Received 12 May 2020 San Jorge Huesca), Dra Lourdes Mateo (Hospital Universitario Germans Trias i Revised 21 May 2020 Pujol). Accepted 22 May 2020 Contributors CS-­P and JA-­G contributed to the design of the project interpretation Ann Rheum Dis 2020;79:988–990. doi:10.1136/annrheumdis-2020-217948 and analysis of the data and writing of the manuscript. D-­TC, JM and JG-­R contributed to the collection of data, interpretation and analysis of the data and ORCID iDs review of the manuscript. JMP-­R, IR-­F and MAG-­G contributed to the interpretation Cesar Diaz-­Torne http://​orcid.​org/​0000-​0001-​6275-​7699 of the data and review of the manuscript. Íñigo Rúa-­Figueroa http://​orcid.​org/​0000-​0002-​7894-​1690 Funding The authors have not declared a specific grant for this research from any Miguel A Gonzalez-­Gay http://​orcid.​org/​0000-​0002-​7924-​7406 funding agency in the public, commercial or not-­for-­profit sectors. Jose M Alvaro-­Gracia http://​orcid.​org/​0000-​0002-​0343-​3747 Competing interests None declared. References Patient and public involvement Patients and/or the public were not 1 (CCAES) CdCdAyES.. Enfermedad POR nuevo coronavirus, COVID-19. Situación involved in the design, or conduct, or reporting, or dissemination plans of this actual, 2020. Available: https://www.​mscbs.​gob.​es/p​ rofesionales/​saludPublica/​ccayes/​ research. alertasActual/​nCov-​China/​documentos/​Actualizacion_1​ 11_​COVID-1​ 9.​pdf [Accessed cited 2020 21/05/2020]. Patient consent for publication Not required. 2 Neurath MF. Covid-19 and immunomodulation in IBD. Gut 2020;382:gutjnl-2020-321269. Provenance and peer review Not commissioned; externally peer reviewed. 3 Monti S, Balduzzi S, Delvino P, et al. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 2020;79:667–8. 4 Haberman R, Axelrad J, Chen A, et al. Covid-19 in immune-­mediated inflammatory diseases — case series from New York. N Engl J Med Overseas Ed 2020. 5 Favalli EG, Ingegnoli F, De Lucia O, et al. COVID-19 infection and rheumatoid arthritis: This is an open access article distributed in accordance with the Creative Commons Faraway. so close! Autoimmunity reviews 2020;102523. Attribution Non Commercial (CC BY-­NC 4.0) license, which permits others to 6 Gianfrancesco MA, Hyrich KL, Gossec L, et al. Rheumatic disease and COVID-19: initial distribute, remix, adapt, build upon this work non-­commercially, and license their data from the COVID-19 global rheumatology alliance provider registries. The Lancet derivative works on different terms, provided the original work is properly cited, Rheumatology 2020. 990 Ann Rheum Dis July 2020 Vol 79 No 7