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Effects of chronic exposure of hydroxychloroquine/ chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases

Authors Fardet L, Nazareth I, Petersen I

Received 9 June 2017

Accepted for publication 2 October 2017

Published 3 November 2017 Volume 2017:9 Pages 545—554


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Henrik Toft Sørensen

L Fardet,1–3 I Nazareth,1 I Petersen1

1Department of Primary Care and Population Health, University College London, UK; 2Department of Dermatology, Henri Mondor Hospital AP-HP, Créteil, France; 3Equipe d’Accueil 7379 EpiDermE, Université Paris Est Créteil, Créteil, France

Background: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases.
Methods: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database.
Results: Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6%) or chloroquine (1.4%) and 24,118 unexposed individuals were included in the study (median age: 56 [45–66] years, women: 76.8%). When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92–1.18], p=0.54), hematological malignancies (adjusted sHR: 1.00 [0.73–1.38], p=0.99), or skin cancers (adjusted sHR: 0.92 [0.78–1.07], p=0.26). The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44–0.95] for the overall population and 0.61 [0.38–1.00] for those diagnosed with incident cancers). The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81–1.00] in the overall population and 0.78 [0.64–0.96] in those diagnosed with incident cancer).
Conclusion: Individuals on long-term exposure to hydroxychloroquine/chloroquine are not at lower risk of cancer. However, hydroxychloroquine/chloroquine may lower the risk of metastatic cancer and death.

Keywords: antimalarial drugs, cancer, death, connective tissue diseases

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