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.
1 Fölster-Holst R, et al. Late-breaking abstract D3T01.1J, EADV 2019, 9-13 Oct, Madrid, Spain.
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