Children that regularly use the topical calcineurin inhibitor tacrolimus over more than 10 years face no elevated risk of cancer. This was the result of an observational study including more than 44,000 patient-years of follow-up .
“Atopic dermatitis is a chronic disease requiring long-term treatment. Therefore, we need prospective safety studies to evaluate the cancer risk,” said Prof. Regina Fölster-Holst (University Medical Center Schleswig-Holstein, Germany). A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis (APPLES™) is an international observational study designed to address the possibility of increased lymphoma or other cancer risk in patients treated long-term with topical calcineurin inhibitors.
The primary outcome was occurrence of any malignancy. In addition, incidences of lymphoma or cutaneous malignant melanoma were assessed. Standardised incidence ratios for cancer events were compared to sex-, age-, and race-matched background population data from national cancer registries.
Between May 2005 and August 2012, APPLES enrolled 7,954 eligible patients at 314 sites in 9 North American and European countries. Participants were children with atopic dermatitis (AD) with exposure to topical tacrolimus for at least 6 weeks and who were first exposed before the age of 16. Most patients suffered from modest-to-severe AD, and the majority also had other atopic diseases. Patients were observed over 10 years under actual-use conditions, with regular clinic visits and completion of questionnaires by the patients or their parents or caregivers. Median study persistence was 6.4 years, with 14.7% of patients remaining on-study for ≥ 10 years. In 2019, the FDA endorsed an early stop in 2019 due to futility of continuation as they thought it unlikely that continued observations could alter the study findings.
During the study, 6 cases of cancer occurred but no lymphoma. No difference was observed in cancer incidence to the matched background population data. “Even if we increase the hypothetical incidence to 2.5, the cancer incidence would remain non-significantly elevated over the expected background population rate,” said Prof. Fölster-Holt.
With regard to the safety of the product, it is very reassuring that there has been no incidence of lymphomas and only one case of skin cancer was observed over more than 44,000 patient-years of follow-up. As the evaluation only included data on tacrolimus, the results cannot be transferred to other calcineurin inhibitors like pimecrolimus.
- Fölster-Holst R, et al. Late-breaking abstract D3T01.1J, EADV 2019, 9-13 Oct, Madrid, Spain.
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Table of Contents: EADV 2019
Letter from the Editor
IL-17A blocker effective in paediatric psoriasis patients
Rituximab beats mycophenolate mofetil in pemphigus vulgaris
Novel JAK1/2 inhibitor shows remarkable efficacy in alopecia areata
Acne highly influenced by climate, pollutants, and unhealthy diet
JAK inhibition plus TCS lead to high clearance rates in AD
No cancer risk with long-term use of tacrolimus, a topical calcineurin inhibitor, in children with AD
Green light for a second JAK inhibitor in AD
Topical ruxolitinib effective in vitiligo
Small molecules: interesting novel treatment options in AD
IL-1⍺ blockade: a new treatment option in AD
IL-4/IL-13 blockade leads to rapid itch reduction in adolescents
How to manage conjunctivitis in AD patients treated with a biologic
Biologics: increasingly used in paediatric dermatology
Spotlight on Psoriasis
IL-17 blocker: effective and safe in patients with comorbidities
ESPRIT registry: sharp decline in mortality in patients treated with a TNF blocker
Relationship psoriasis and NAFLD: new data on the hepato-dermal axis
Novel selective IL-23 blocker equally effective in patients with metabolic syndrome
Selective IL-23 blocker crushes fumaric acids in all assessed efficacy endpoints
No hint of teratogenicity through ixekizumab
New Insights in Photoprotection
Systemic photoprotection: a valuable addition to topical sun protection
The underestimated effect of visible light
Comorbidities more common in chronic urticaria, psoriasis, and AD
D-Dimer as future biomarker in CSU management?
Ligelizumab for CSU: symptom control and high response rates in re-treatment
Rosacea – From New Spectrum to New Therapy
New guidance on rosacea therapy according to phenotype
Best of the Posters
Above-the-neck melanoma more prone to metastases
Reduced sleep quality in dermatoses influenced by itch and pain
Anxiety and depression are common in families of AD infants
Certolizumab pegol efficacious for head and neck psoriasis
Biologic psoriasis treatment to lower cardiovascular risk?
Systemic treatment for psoriasis: what is on the horizon?