Voriconazole exposure and risk of cutaneous squamous cell carcinoma, Aspergillus colonization, invasive aspergillosis and death in lung transplant recipients

M. Mansh, M. Binstock, K. Williams, F. Hafeez, J. Kim, D. Glidden, R. Boettger, S. Hays, J. Kukreja, J. Golden, M. M. Asgari, P. Chin-Hong, J. P. Singer, S. T. Arron

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40 Scopus citations

Abstract

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. The authors associate voriconazole with an increased risk for squamous cell carcinoma in lung transplant recipients, but a reduction in all-cause mortality in patients colonized with Aspergillus.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalAmerican Journal of Transplantation
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
MM is supported by the Stanford University Medical Scholars Research Grant. PCH is supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through the University of California, San Francisco, Clinical and Translational Science Institute (UCSFCTSI grants UL1 TR000004 and TL1 TR000144). JS is supported by the NIH/National Heart, Lung, and Blood Institute, through grant K23 HL111115. SA is supported by UCSF-CTSI grant KL2 TR000143. This study was supported by the UCSF Nina Ireland Lung Disease Program. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the US Department of Health and Human Services. The funding agencies played no role in the collection, analysis, interpretation, or publication of this data.

Publisher Copyright:
Copyright © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

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