Alegiani SS, Crisafulli S, Rossi PG, Mancuso P, Salvarani C, Atzeni F, Gini R, Kirchmayer U, Belleudi V, Kurotschka PK, Leoni O, Ludergnani M, Ferroni E, Baracco S, Massari M, Trifirò G; ITA-COVID-19 Network.

Rheumatology (Oxford). 2021 Apr 15:keab348. doi: 10.1093/rheumatology/keab348. Online ahead of print.


Objectives: To ascertain if hydroxychloroquine (HCQ)/chloroquine (CLQ) and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) use, 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. Risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis, comparing HCQ/CLQ vs methotrexate, vs other cDMARDs and vs non-use of these drugs. Presence of rheumatic diseases vs their absence in a non-nested population was investigated.

Results: 1275 cases hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of methotrexate, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization (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 to 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 methotrexate 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. 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 to be ascribed to immunosuppressive action.

Keywords: Antirheumatic agents; COVID-19; Chloroquine; Hydroxychloroquine; outpatients.

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