Population Pharmacokinetics of Intravenous and Subcutaneous Belimumab, and Clinical Response Prediction in Chinese Pediatric Patients with Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVE: Intravenous (IV) and subcutaneous (SC) belimumab are approved in the USA, Europe, and Japan for patients aged ≥ 5 years with active systemic lupus erythematosus. In China, IV belimumab is approved for patients aged ≥ 5 years. This analysis updates the global pediatric population pharmacokinetic model by integrating data from IV and SC Chinese pediatric studies and evaluates the suitability of a 200-mg SC dosing regimen for pediatric systemic lupus erythematosus in China.

METHODS: This analysis utilized the previously established two-compartment model while re-evaluating the impact of potential covariates. Allometric scaling was incorporated to account for variations in body size, and other covariates were systematically assessed through stepwise selection and their relevance to pharmacokinetic parameters. To support extrapolation of the established efficacy from the IV belimumab pediatric study to SC belimumab in pediatric patients, simulations were conducted to compare pharmacokinetic exposures between the proposed SC and approved IV regimens in Chinese pediatric patients. Furthermore, to provide additional evidence for supporting dose selection in this population, clinical response was predicted using a pre-established exposure-response model.

RESULTS: The estimated pharmacokinetic parameters for a representative Chinese pediatric patient were: clearance, 158 mL/day; steady-state volume of distribution, 3930 mL; SC bioavailability, 77.9%. Identified significant covariates included body weight (influencing clearance and volume of distribution), and baseline immunoglobulin G and albumin levels (affecting clearance). A systematic bias of -34% in drug concentrations was observed in Chinese versus global studies. This discrepancy is unlikely to stem from racial or physiological differences and may instead be attributed to study operational factors. The established exposure-response model confirmed that simulated exposures for IV and SC regimens in Chinese pediatric patients reached the plateau of the exposure-response curve. Further simulations demonstrated that both the two-weight-band SC regimen and the trial-studied three-weight-band regimen produced exposures comparable to the IV regimen in Chinese pediatric patients.

CONCLUSIONS: This analysis supports the suitability of a two-weight-band, dosing interval-adjusted 200-mg SC regimen for Chinese pediatric patients with systemic lupus erythematosus. Compared with the three-weight-band regimen, the two-weight-band approach simplifies administration and enhances feasibility for clinical implementation.