Population-Based Pharmacodynamic Modeling of Omalizumab in Pediatric Patients with Moderate to Severe Persistent Inadequately Controlled Allergic Asthma

Abstract

Omalizumab is the first approved anti-immunoglobulin E (IgE) agent for the treatment of moderate to severe persistent inadequately controlled allergic asthma in adults and adolescents (≥ 12 years old). In 2016, it was approved in pediatric patients (6–11 years old). The objective of this study was to quantitatively characterize the relationship between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) in pediatrics using a population-based pharmacodynamic model. Data collected during the steroid-stable period (first 24 weeks) of an omalizumab trial with pediatric asthma patients (Study IA05) were used to build the pediatric IgE–FEV1 model. The previously developed population IgE–FEV1 model in adults/adolescents was adapted to characterize the FEV1 and IgE relationship in pediatrics with different magnitude and onset of response. The pediatric IgE–FEV1 model adequately characterized the IgE–FEV1 relationship in pediatrics, particularly at the extremes of the observed body weights (i.e., ≤ 30 kg) and IgE values at screening (i.e., > 700 IU/mL). The estimated sigmoidal free IgE–FEV1 curves were similar in shape and maximum effect, but the estimated free IgE concentration leading to 50% maximum effect (IC50) in pediatric patients (39.4, 95% confidence interval [CI] 24.3–63.9 ng/mL) was higher than estimated in adults (19.8, 95% CI 15.1–24.5 ng/mL). The model further confirmed that the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml was appropriate. The pediatric model can be used to predict population FEV1 response for omalizumab when combined with an omalizumab pharmacokinetic–IgE model.Graphical abstract