BACKGROUND: Observations of transplant recipients receiving systemic calcineurin inhibitors have raised concern of a potentially increased risk of lymphoma and skin cancer with topical use of tacrolimus (TAC) or pimecrolimus (PIM) for atopic dermatitis.
OBJECTIVES: To estimate the long-term risk of skin cancer and lymphoma associated with use of topical TAC or PIM in adults and children
METHODS: A multinational cohort study was conducted using available health data from 2002 through 2017 in the United Kingdom’s Clinical Practice Research Datalink, the PHARMO Database Network in the Netherlands, and the Danish and Swedish nationwide health registers. Mantel-Haenszel methods were used to estimate incidence rate ratios (IRRs) and differences in children and adults of study malignancies, comparing new users of topical TAC and topical PIM with two propensity score-matched cohorts of users of moderate- to high-potency topical corticosteroids. Malignancies included Hodgkin’s lymphoma, non-Hodgkin’s lymphoma other than cutaneous T-cell lymphoma (CTCL), CTCL, and skin cancer (melanoma and nonmelanoma).
RESULTS: The study included 126,908 adults and 32,605 children initiating treatment with topical TAC and 61,841 adults and 27,961 children initiating treatment with topical PIM. Follow-up was 10 years or more for 19.4% of adults and for 31.9% of children. Among adults and children, the median number of topical TAC or PIM prescriptions was one, and for the 80th percentile, three. In adults, IRRs were not increased other than the IRR of CTCL for topical TAC: 1.80 (95% confidence interval [CI], 1.25-2.58) corresponding to an excess rate of 3 cases per 100,000 person-years (95% CI, 1-6). The IRR of melanoma for topical PIM was 1.21 (95% CI, 1.03-1.41) for an excess rate of 10 cases per 100,000 person-years (95% CI, 1-18). The IRR of nonmelanoma skin cancer for topical PIM was 1.28 (95% CI, 1.20- 1.35) for an excess rate of 91 cases per 100,000 person-years (95% CI, 68-114). In children, results were inconclusive due to few events. For adult users of topical TAC in whom the time since first exposure to treatment was ≥ 5 years, the IRR for CTCL was 0.25 (95% CI, 0.03-1.87).
CONCLUSION: Overall, we found little evidence associating use of topical TAC and topical PIM with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. If there were a causal association, our data indicate that any public-health impact of CTCL associated with the use of topical TAC and of skin cancer associated with the use of topical PIM would be low.
