title: Risk-adjusted relationship between voriconazole utilization and non-melanoma skin cancer among lung and heart/lung transplant patients.
abstract: BACKGROUND
  We examined the relationship between voriconazole utilization and non-melanoma skin cancer (NMSC) development among adult lung and heart/lung transplant patients who were continuously enrolled in a large U.S. commercial health plan.
  
  
  METHODS
  Cox proportional hazards regression models were constructed to assess both the crude and adjusted effect of voriconazole usage on NMSC development. Overall, 467 adult lung (98%) and heart/lung (2%) transplant patients (60% male) with median age of 58 years were analyzed.
  
  
  RESULTS
  Fifty-seven (12%) patients developed NMSC over a median follow-up time of 610 days. At the crude level, patients with any (vs. none) claim for voriconazole were more likely to develop NMSC (19% vs. 12%, hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.02, 2.96, P = 0.04). However, after statistical adjustment for demographic and clinical factors, the effect was largely diminished and no longer statistically significant (HR: 1.23, 95% CI: 0.71, 2.14, P = 0.45). Results were similar when modeling average and total dose of voriconazole. Risk factors significantly related to NMSC development were being male, older age, sun exposure, history of chronic obstructive pulmonary disorder, and history of immune disorder.
  
  
  CONCLUSIONS
  Results suggest that the relationship between voriconazole utilization and NMSC among lung transplant patients may be a result of confounding by indication, and that controlling for underlying patient characteristics is paramount.
authors.affiliation: Pfizer, Inc, New York, New York, USA. john.mclaughlin@pfizer.com
authors.forename: J M
authors.initials: JM
authors.lastname: McLaughlin
authors.forename: O
authors.initials: O
authors.lastname: Equils
authors.forename: K T
authors.initials: KT
authors.lastname: Somerville
authors.forename: J A
authors.initials: JA
authors.lastname: Aram
authors.forename: H T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: V L
authors.initials: VL
authors.lastname: Welch
authors.forename: J
authors.initials: J
authors.lastname: Mardekian
authors.forename: R G
authors.initials: RG
authors.lastname: Barbers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000517:prevention & control; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000453:epidemiology*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000453:epidemiology*; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole
keywords: confounding; heart/lung transplant; immunosuppression; lung transplant; non-melanoma skin cancer; risk adjustment; statistical adjustment; voriconazole