Association Between Exposure to Topical Tacrolimus or Pimecrolimus and Cancers

BACKGROUND: The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors. OBJECTIVE: To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors. METHODS: A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model. RESULTS: Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% Cl 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% Cl 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% Cl 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% Cl 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% Cl 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma. CONCLUSIONS: Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.