Association Between Malignancy and Topical Use of Pimecrolimus

JAMA Dermatol. 2015 Jun;151(6):594-9. doi: 10.1001/jamadermatol.2014.4305.

Abstract

Importance: A black box warning describes a potential risk of malignancy associated with topical use of pimecrolimus to treat atopic dermatitis due to its similarity to oral calcineurin inhibitors used in solid-organ transplantation and spontaneous reporting of malignancies, including lymphomas and cutaneous malignancies.

Objective: To evaluate the risk of malignancy in a postmarketing study of children exposed to pimecrolimus.

Design, setting, and participants: A longitudinal cohort study among a nationwide ongoing long-term cohort of children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of atopic dermatitis and pimecrolimus use with data available up through May 2014.

Main outcomes and measures: Reports of malignancy among those in the PEER compared with expected rates from the Surveillance, Epidemiology, and End Results (SEER) program.

Results: Overall, 7457 children were enrolled in the PEER, for a total of 26,792 person-years. Children used a mean (SD) of 793 (1356) g of pimecrolimus when enrolled in the study. As of May 2014, five malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The standardized incidence ratio for all malignancies (primary outcome) based on the age-standardized SEER population was 1.2 (95% CI, 0.5-2.8). As secondary analyses, the standardized incidence ratios (based on 2 cases for each) were 2.9 (95% CI, 0.7-11.7) for lymphoma and 2.0 (95% CI, 0.5-8.2) for leukemia. None of these findings were statistically significant.

Conclusions and relevance: Based on more than 25,000 person-years of follow-up, it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat atopic dermatitis is associated with an increased risk of malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dermatitis, Atopic / drug therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Longitudinal Studies
  • Male
  • Neoplasms / epidemiology
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Registries
  • Risk
  • SEER Program
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Tacrolimus / analogs & derivatives*

Substances

  • Immunosuppressive Agents
  • pimecrolimus
  • Tacrolimus