Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy
Alegiani et al.
, Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other..
, Rheumatology, doi:10.1093/rheumatology/keab348
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
risk of death, 8.0% higher, OR 1.08, p = 0.64, HCQ vs. other cDMARDs, RR approximated with OR.
risk of hospitalization, 18.0% lower, OR 0.82, p = 0.03, HCQ vs. other cDMARDs, RR approximated with OR.
risk of death, 19.0% higher, OR 1.19, p = 0.32, HCQ vs. MTX, RR approximated with OR.
risk of hospitalization, 12.0% lower, OR 0.88, p = 0.17, HCQ vs. MTX, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Alegiani et al., 15 Apr 2021, retrospective, case control, database analysis, Italy, peer-reviewed, 16 authors.
Advance Access publication 15 April 2021
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
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
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,
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..
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