Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study

Abstract

Nooral systemic treatments are approved for pediatric patients with psoriasis. To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2weeks (group 1 [age, 12-17years; weight, ≥35kg]: apremilast 20 or 30mg; group 2 [age, 6-11years; weight, ≥15kg]: apremilast 20mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. A total of 42 enrolled patients (21 adolescents [age, 12-17years] and 21 children [age, 6-11years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20mg twice daily in children or apremilast 20 or 30mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12hours after the dose) that is comparable to that achieved with apremilast 30mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. No children weighing less than 20kg were enrolled. This first-time-in-children phase 2 study supports weight-based apremilast dosing for futurephase 3 studies of pediatric plaque psoriasis.