AAD: Tacrolimus Safe for Kids, Phase IV Study Finds


MIAMI – Long-term use of tacrolimus ointment in children with atopic dermatitis is associated with a low rate of serious adverse events, according to interim data from a prospective study.

The safety profile shown thus far is consistent with the established profile for tacrolimus ointment (Protopic), and it is hoped that these findings will encourage dermatologists to continue enrolling pediatric patients in this ongoing phase IV safety study, Dr. Joyce Rico said in a poster presentation at the annual meeting of the American Academy of Dermatology.

The interim report focused on 4,800 patients enrolled in APPLES (A Prospective Pediatric Longitudinal Evaluation Study) between May 2005 and September 2009. The investigators seek to enroll 8,000 children in the multinational, observational cohort study, said Dr. Rico, vice president of medical science at Astellas Pharma Inc., Chicago.

That is the number needed to accurately identify an increase in the risk of malignancy associated with tacrolimus treatment over the course of the 10-year study, but the investigators are also evaluating other serious adverse events.

Such events occurred in about 5% of the participants, who had a median age of 6 years at enrollment. Most of the serious events were asthma, occurring in 1% of patients, and infectionsincluding pneumonia, bronchitis, cellulitis, gastroenteritis, and tonsillitis – occurring in nearly 2% of patients. There was one report of a malignancy – a peripheral glioneuronal tumor – not typically associated with immunosuppression, Dr. Rico noted.

The malignancy rate in APPLES is half that seen in the general U.S. population, based on data from the Surveillance, Epidemiology, and End Results database, she said.

About 40% of children in APPLES had mild disease at baseline and about 60% reported moderate or severe disease. Treatment is either 0.03% ointment (the dosage approved for children) or off-label 0.1% ointment (the dosage approved for adults); most are being treated with 0.1% ointment. The median cumulative duration of time since initial treatment application is 2.8 years per patient.

“The serious adverse events profile we’re seeing is consistent with what was observed during the clinical development program,” Dr. Rico said, noting that, although the results are encouraging, enrollment of the full 8,000 patients is needed to adequately address the long-term safety of tacrolimus treatment in children.

“I encourage you and your colleagues to continue to enroll patients ... It’s going to take the dermatology community continuing to help us to reach that goal,” she concluded.

Dr. Rico is employed by Astellas, the maker of Protopic and sponsor of the study.

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