Atopic dermatitis (AD or eczema ) affects up to 20% of children, but treatment options are limited. The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus (Elidel is the commercial name) were approved in 2000 and 2001 respectively for AD therapy. Systemic use of TCIs has been associated with increased malignancy risk, especially skin cancer and lymphoma. A black-box warning was added to topical pimecrolimus labeling in 2005.
The Pediatric Eczema Elective Registry (PEER) is an ongoing, nationwide longitudinal cohort study started in 2004 to gather post-marketing data in patients who used pimecrolimus cream for at least 42 days of the 180 preceding enrollment. Subsequent treatment is not required, and AD management is dictated by the patient’s physician. The primary outcome is onset of any malignancy after enrollment; participants are queried every 6 months about malignancy.
As of May 2014, five malignancies were reported in 7457 children enrolled and followed for 26,792 person-years (2 leukemias, 1 osteosarcoma, 2 lymphomas, no skin cancers). The overall rate of malignancy was 18.7/100,000 person-years. The standardized incidence ratio for all malignancies based on age-standardized SEER population was 1.2 (95% confidence interval, 0.5–2.8), a statistically insignificant risk. The authors conclude that increased malignancy risk is unlikely to be associated with topical pimecrolimus as used in the PEER cohort.
Topical calcineurin inhibitors such as Elidel were heavily marketed when they first came to market and were a welcome alternative to topical corticosteroids. The rapid rise in prescriptions coupled with malignancy concerns led to the black-box warning, which swung the pendulum to the other extreme. Physicians, pharmacists, and parents became afraid to use TCIs despite the lack of evidence associating them with malignancy. The PEER registry, one of the largest prospective, longitudinal studies ever conducted in dermatology, is nearing completion. Thus far, malignancy is no more frequent in this cohort than in the general pediatric population, a reassuring conclusion.