Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy

Stefania Spila Alegiani; Salvatore Crisafulli; Paolo Giorgi Rossi; Pamela Mancuso; Carlo Salvarani; Fabiola Atzeni; Rosa Gini; Ursula Kirchmayer; Valeria Belleudi; Peter Konstantin Kurotschka; Olivia Leoni; Monica Ludergnani; Eliana Ferroni; Susanna Baracco; Marco Massari; Gianluca Trifirò; ITA-COVID-19 Network

doi:10.1093/rheumatology/keab348

Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy

Rheumatology (Oxford). 2021 Oct 9;60(SI):SI25-SI36. doi: 10.1093/rheumatology/keab348.

Authors

Stefania Spila Alegiani¹, Salvatore Crisafulli^{2

3}, Paolo Giorgi Rossi⁴, Pamela Mancuso⁴, Carlo Salvarani^{5

6}, Fabiola Atzeni⁷, Rosa Gini⁸, Ursula Kirchmayer⁹, Valeria Belleudi⁹, Peter Konstantin Kurotschka^{10

11}, Olivia Leoni¹², Monica Ludergnani¹², Eliana Ferroni¹³, Susanna Baracco¹³, Marco Massari¹, Gianluca Trifirò^{3

14}; ITA-COVID-19 Network

Affiliations

¹ Pharmacoepidemiology Unit, National Centre for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
² Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
³ Italian Society of Pharmacology, Milan, Italy.
⁴ Epidemiology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
⁵ Unit of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
⁶ Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy.
⁷ Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy.
⁸ Agenzia Regionale di Sanità della Toscana, Florence, Italy.
⁹ Department of Epidemiology ASL Roma 1, Lazio Regional Health Service, Rome, Italy.
¹⁰ Department of Medical Sciences and Public Health, Faculty of Medicine and Surgery, University of Cagliari, Cagliari, Italy.
¹¹ Regional Health Trust of Sardinia Region, Cagliari, Italy.
¹² Epidemiology Observatory-Department of Health of Lombardy Region, Milan, Italy.
¹³ Azienda Zero of the Veneto Region, Padua, Italy.
¹⁴ Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Abstract

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-19-related 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.

Keywords: COVID-19; anti-rheumatic agents; chloroquine; hydroxychloroquine; outpatients.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Antirheumatic Agents / therapeutic use*
COVID-19 / mortality
COVID-19 Drug Treatment*
Case-Control Studies
Drug Therapy, Combination
Female
Glucocorticoids / therapeutic use
Hospitalization / statistics & numerical data*
Humans
Hydroxychloroquine / therapeutic use*
Italy
Male
Middle Aged
Odds Ratio
Population Surveillance
Rheumatic Diseases / drug therapy*
Rheumatic Diseases / virology
SARS-CoV-2
Young Adult

Substances

Antirheumatic Agents
Glucocorticoids
Hydroxychloroquine

Grants and funding

Italian National Institute of Health