No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis

Amy S. Paller; Regina Fölster-Holst; Suephy C. Chen; Thomas L. Diepgen; Craig Elmets; David J. Margolis; Brad H. Pollock

doi:10.1016/j.jaad.2020.03.075

No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis

Amy S. Paller^*, Regina Fölster-Holst, Suephy C. Chen, Thomas L. Diepgen, Craig Elmets, David J. Margolis, Brad H. Pollock

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

Background: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. Objective: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. Methods: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. Results: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. Limitations: Observational prospective cohort study. Conclusion: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

Original language	English (US)
Pages (from-to)	375-381
Number of pages	7
Journal	Journal of the American Academy of Dermatology
Volume	83
Issue number	2
DOIs	https://doi.org/10.1016/j.jaad.2020.03.075
State	Published - Aug 2020

Funding

A complete listing of APPLES study sites is available at https://data.mendeley.com/datasets/sxgkpjdxsw/1. We gratefully acknowledge the study center personnel and patients and also thank John Ashkenas, PhD, for medical writing support, made possible by LEO Pharma in accordance with Good Publication Practice guidelines. Funding sources: The APPLES study (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis) was initiated by Fujisawa and later sponsored by Astellas Pharma and LEO Pharma. LEO Pharma Inc, provided medical writing assistance for this publication.

Keywords

atopic dermatitis
cancer risk
lymphoma
skin cancer
tacrolimus
topical calcineurin inhibitors

ASJC Scopus subject areas

Dermatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaad.2020.03.075

Cite this

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title = "No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis",

abstract = "Background: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. Objective: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. Methods: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. Results: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. Limitations: Observational prospective cohort study. Conclusion: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.",

keywords = "atopic dermatitis, cancer risk, lymphoma, skin cancer, tacrolimus, topical calcineurin inhibitors",

author = "Paller, {Amy S.} and Regina F{\"o}lster-Holst and Chen, {Suephy C.} and Diepgen, {Thomas L.} and Craig Elmets and Margolis, {David J.} and Pollock, {Brad H.}",

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doi = "10.1016/j.jaad.2020.03.075",

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AU - Chen, Suephy C.

AU - Diepgen, Thomas L.

AU - Elmets, Craig

AU - Margolis, David J.

AU - Pollock, Brad H.

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N2 - Background: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. Objective: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. Methods: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. Results: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. Limitations: Observational prospective cohort study. Conclusion: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

AB - Background: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. Objective: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. Methods: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. Results: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. Limitations: Observational prospective cohort study. Conclusion: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

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KW - cancer risk

KW - lymphoma

KW - skin cancer

KW - tacrolimus

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No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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