Castellsague J, van Herk-Sukel MPP, Hallas J, Sundstrom A, Gallagher A, Gutierrez L, Calingaert B, Kuiper JG, Pottegard A, Berglind IA, Dedman D, Kaye JA, Pardo C, Rothman KJ, Perez-Gutthann S. Risk of skin cancer in users of topical tacrolimus, pimecrolimus, and corticosteroids. JOint European Longitudinal Lymphoma and skin cancer Evaluation (JOELLE) study. Poster presented at the 32nd ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 28, 2016. Dublin, Ireland. [abstract] Pharmacoepidemiol Drug Saf. 2016 Aug; 25(Suppl 3):527.

BACKGROUND: Topical tacrolimus is indicated for the treatment of moderate to severe atopic dermatitis, and topical pimecrolimus for the treatment of mild to moderate atopic dermatitis. Data on the risk of skin cancer associated with use of these medications are scarce.

OBJECTIVES: To estimate incidence rate ratios (IRRs) of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) comparing new users of tacrolimus and pimecrolimus with current users of moderateto highpotency topical corticosteroids (TCS), and users of TCS with general population untreated subjects.

METHODS: Cohort study in the PHARMO Database Network (Netherlands), the Danish and Swedish national registers, and the Clinical Practice Research Datalink (United Kingdom), with RTI Health Solutions acting as coordinating/pooled analysis center. New users of tacrolimus and pimecrolimus were frequency matched to users of TCS on twentiles of propensity scores; users of TCS were individually matched to untreated subjects on age, sex, region, and calendar year. We estimated IRRs and 95% confidence intervals (CI) using MantelHaenszel methods.

RESULTS: We included (a) 19,948 children and 66,127 adults treated with tacrolimus matched with 79,700 children and 264,482 adults treated with TCS; (b) 23,840 children and 37,417 adults treated with pimecrolimus matched with 90,268 children and 149,671 adults treated with TCS; and (c) 79,040 children and 257,074 adults untreated with any study medication. In adults, the adjusted IRR (95% CI) for tacrolimus vs. TCS was 0.90 (0.661.22) for MM and 1.08 (0.981.19) for NMSC. The IRR for pimecrolimus vs. TCS was 1.16 (0.871.56) for MM and 1.20 (1.071.35) for NMSC. IRRs for TCS vs. untreated were 0.87 (0.741.03) for MM and 1.19 (1.111.27) for NMSC. In children, the number of events was too small to draw conclusions.

CONCLUSIONS: These results suggest little or no effect of tacrolimus and pimecrolimus on the risk of skin cancer. Estimates were close to the null, and residual confounding by severity of atopic dermatitis and surveillance bias cannot be ruled out.