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.


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


  • Antirheumatic Agents
  • Glucocorticoids
  • Hydroxychloroquine