A Population Pharmacokinetic and Exposure-Response Analysis for Baricitinib in Pediatric Patients with Atopic Dermatitis.

BACKGROUND

Baricitinib is approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy and has received regulatory authorization in Europe for moderate-to-severe AD in patients 2 to <18 years.

OBJECTIVE

This study aims to optimize dosing for baricitinib in pediatric patients with atopic dermatitis using pharmacokinetic/pharmacodynamic modeling leveraging adult data.

METHODS

The phase III, randomized, double-blind, placebo-controlled study, BREEZE-AD-PEDS (NCT03952559, registration date: 2019-05-16), enrolled patients (aged 2 to <18 years) with moderate-to-severe AD. During a pharmacokinetic (PK) lead-in period, baricitinib concentration data from age-based dose cohorts (4 mg once daily [QD]: 10 to <18 years; 2 mg QD: 2 to <10 years) were compared with actual and simulated concentration values from adult patients receiving baricitinib 4 mg QD. A population PK model incorporating allometric scaling was developed to determine weight-based dosing in pediatric patients that matches adult exposures. The exposure-response (E-R) relationships were analyzed for the primary endpoint: a validated Investigator Global Assessment® (vIGA-AD) score of 0 or 1 (clear to almost clear skin) with ≥2-point improvement from baseline at week 16. Baricitinib pharmacokinetics were characterized from 393 pediatric patients using a 2-compartment model with allometric scaling on clearance and volume of distribution.

RESULTS

The age-based and subsequent weight-based dosing (2 mg for patients 10 to <30 kg and 4 mg for patients ≥30 kg) was comparable to the 4-mg adult exposure. A clear E-R relationship was observed for the primary endpoint when sorted for age or weight groups.

CONCLUSION

The population PK model developed using baricitinib concentrations from adult patients, with allometric scaling for weight on clearance and volume, adequately predicted exposures in the pediatric population. The PK modeling, with E-R analysis, informed an appropriate weight-based dosing regimen.