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

https://doi.org/10.1016/j.jaad.2019.08.019Get rights and content
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Background

No oral systemic treatments are approved for pediatric patients with psoriasis.

Objective

To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis.

Methods

This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), 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.

Results

A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg 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.

Limitations

No children weighing less than 20 kg were enrolled.

Conclusions

This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.

Key words

adolescent
apremilast
children
pediatric
pharmacokinetics
plaque psoriasis
safety

Abbreviations used

AE
adverse event
AUC0-12
area under the concentration-time curve from time 0 to 12 hours after the dose
AUC0-t
area under the concentration-time curve from time 0 to the last quantifiable concentration
BMI
body mass index
BSA
body surface area
CL/F
apparent total plasma clearance
Cmax
maximal observed plasma concentration
PASI
Psoriasis Area and Severity Index
PK
pharmacokinetic
TEAE
treatment-emergent adverse event

Cited by (0)

Funding sources: Supported by Celgene Corporation.

Disclosure: Dr Paller has received honoraria as a consultant for Asana, Dermira, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, UCB, and Valeant and has been an investigator without personal compensation for AbbVie, Celgene Corporation, Eli Lilly, Galderma, Janssen, LEO Pharma, and Novartis. Drs Hong, Paris, W. Zhang, Z. Zhang; Ms Barcellona; and Mr Maes are employees of and may have stock/stock options in Celgene Corporation. Dr Becker is an investigator for Celgene Corporation. Dr Fiorillo has received study grants from Celgene Corporation and payment for attending advisory board meetings from Amgen, AbbVie, and Janssen. Dr de Lucas has no conflicts of interest to declare.

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