Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study

B. Hamandi, C. Fegbeutel, F. P. Silveira, E. A. Verschuuren, M. Younus, J. Mo, J. Yan, P. Ussetti, P. V. Chin-Hong, A. Solé, C. L. Holmes-Liew, E. M. Billaud, P. A. Grossi, O. Manuel, D. J. Levine, R. G. Barbers, D. Hadjiliadis, J. Aram, L. G. Singer, S. Husain

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC.
EU PAS registration number: EUPAS5269.

Original languageEnglish (US)
Pages (from-to)113-124
Number of pages12
JournalAmerican Journal of Transplantation
Volume18
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • antibiotic: antifungal
  • clinical research/practice
  • complication: malignant
  • health services and outcomes research
  • infection and infectious agents - fungal
  • infectious disease
  • lung disease
  • lung transplantation/pulmonology
  • patient safety

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Hamandi, B., Fegbeutel, C., Silveira, F. P., Verschuuren, E. A., Younus, M., Mo, J., Yan, J., Ussetti, P., Chin-Hong, P. V., Solé, A., Holmes-Liew, C. L., Billaud, E. M., Grossi, P. A., Manuel, O., Levine, D. J., Barbers, R. G., Hadjiliadis, D., Aram, J., Singer, L. G., & Husain, S. (2018). Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study. American Journal of Transplantation, 18(1), 113-124. https://doi.org/10.1111/ajt.14500