Abstract: Rheumatology Rheumatology 2021;60:SI25–SI36 doi:10.1093/rheumatology/keab348 Advance Access publication 15 April 2021 Original article Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy Objectives. To ascertain if the use of hydroxychloroquine(HCQ)/cloroquine(CLQ) and other conventional DMARDs (cDMARDs) and rheumatic diseases per se may be associated with COVID-19-related risk of hospitalization and mortality. Methods. This case–control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. The risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis comparing HCQ/CLQ vs MTX, vs other cDMARDs and vs non-use of these drugs. The presence of rheumatic diseases vs their absence in a non-nested population was investigated. Results. A total of 1275 patients hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of MTX, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization [odds ratio (OR) 0.83 (95% CI 0.69, 1.00)] or mortality [OR 1.19 (95% CI 0.85, 1.67)] was observed. A lower risk was found when comparing HCQ/CLQ use with the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either MTX monotherapy [OR 1.19 (95% CI 1.05, 1.34)] or other cDMARDs [OR 1.21 (95% CI 1.08, 1.36)] vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. Conclusion. HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19related outcomes. The use of other cDMARDs was associated with an increased risk when compared with non-use and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably due to immunosuppressive action. Key words: hydroxychloroquine, chloroquine, anti-rheumatic agents, COVID-19, outpatients 1 Pharmacoepidemiology Unit, National Centre for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, 3Italian Society of Pharmacology, Milan, 4Epidemiology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, 5Unit of Rheumatology, Azienda USLIRCCS di Reggio Emilia, Reggio Emilia, 6Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, 7 Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, 8Agenzia Regionale di Sanità della Toscana, Florence, 9Department of Epidemiology ASL Roma 1, Lazio Regional Health Service, Rome, 10Department of Medical Sciences and Public Health, Faculty of Medicine and Surgery, University of Cagliari, 11Regional Health Trust of Sardinia Region, Cagliari, 12Epidemiology Observatory–Department of Health of Lombardy Region, Milan, 13Azienda Zero of the Veneto Region, Padua and 14Department of Diagnostics and Public Health, University of Verona, Verona, Italy Submitted 9 February 2021; accepted 7 April..