Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

No Tacrolimus/Cancer Link in Atopic Dermatitis in 10-Year Study

Key clinical point: No signal of increased cancer risk was found with up to 10 years use of topical tacrolimus for pediatric atopic dermatitis.

Major finding: The standardized incidence ratio of observed-to-expected cancers was highly reassuring at 1.01.

Study details: The APPLES study included 7,954 children using topical tacrolimus for moderate or severe atopic dermatitis, with 44,629 person-years of follow-up.

Disclosures: The presenter reported having no financial conflicts regarding the study, sponsored by LEO Pharma.


Folster-Holst R. EADV late-breaker.


When the calcineurin inhibitors, tacrolimus and pimecrolimus, were first approved by the FDA, studies in infants to children aged 2 and under had not been completed. Hence, the approval included only patients with atopic dermatitis aged over 24 months. Off-label use in younger children was, and still is, common. Due to theoretical concerns that these cyclosporine drugs may increase the risk for malignancy, especially lymphoma and skin cancer, a boxed warning was applied to the labelling. Data from clinical trials and ongoing monitoring has suggested that systemic drug levels from topical use are almost always quite low, except for the rare transient cases of use for severe eczema with large body area involvement. This and other monitoring surveys have given us comfort, as most suspected, that there is no association between these valuable topical medications and cancer occurrence.— Joseph Fowler, Jr., MD, Clinical Professor of Dermatology, University of Louisville, KY