Comparative assessment of pharmacokinetic parameters between HS016, an adalimumab biosimilar, and adalimumab (Humira®) in healthy subjects and ankylosing spondylitis patients: Population pharmacokinetic modeling

作者：Xiaofeng Zeng, J.-T. Yu, Xiaojie Wu, Yuancheng Chen, Jufang Wu, Xiaoli Yang, Jingjing Wang, J.-Y. Zhang, Guoying Cao · 发表于：Advances in Clinical and Experimental Medicine · 年份：2022 · DOI：10.17219/acem/145947 · 被引用次数：6 · 研究领域：Spondyloarthritis Studies and Treatments、Biosimilars and Bioanalytical Methods、Rheumatoid Arthritis Research and Therapies

BACKGROUND: The HS016 is an adalimumab biosimilar related to the immunoglobulin G1 (IgG1) antibody, with a similar amino acid sequence. OBJECTIVES: To quantify the differences in the pharmacokinetic (PK) parameters of HS016 and adalimumab in healthy individuals and patients with ankylosing spondylitis (AS). MATERIAL AND METHODS: The PK data for HS016 and adalimumab were obtained in a randomized, double-blind, phase 1 clinical study in Chinese healthy subjects after a single-dose subcutaneous administration (136 healthy subjects), and in a randomized, double-blind, phase 3 trial of AS patients who received subcutaneous injection of HS016 or adalimumab once every 2 weeks for 24 weeks (366 AS patients). RESULTS: The time course of HS016 and adalimumab was characterized by a one-compartment model with first-order absorption and elimination kinetics. Age, body weight, creatinine clearance (CLcr) and anti-drug antibody were covariates for the apparent clearance (CL/F); body weight and subject type were significant covariates for the apparent volume of distribution (V/F). The V/F and CL/F were estimated at 11.3 L and 0.0102 L/h. The ratios of the geometric least square (LS) means (HS016 compared to the adalimumab treatment group after multiple doses) in healthy subjects were 97.14 (87.70, 107.59) for the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and 99.14 (90.03, 109.16) for the maximum serum drug concentration within a steady-state dosing...