Population pharmacokinetics analysis of guselkumab in healthy subjects and patients with psoriatic arthritis, plaque psoriasis and palmoplantar pustulosis.

Abstract

Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin 23, is approved for the treatment of plaque psoriasis (PsO) and psoriatic arthritis (PsA), palmoplantar pustulosis (PPP), generalized pustular psoriasis, and erythrodermic psoriasis in various countries. The purpose of this analysis was to develop a comprehensive population pharmacokinetic (PK) model for guselkumab to determine whether PK differs across different disease populations and healthy subjects. A nonlinear mixed-effects modelling approach was used to analyse 23 097 serum PK samples obtained from 2623 healthy subjects and patients with PsO, PsA and PPP across 9 phase 1-3 clinical trials. Guselkumab concentrations were adequately described by a 2-compartment linear PK model with first-order absorption and elimination. Clearance (CL), central and peripheral volume of distribution, intercompartmental flow, absorption rate constant and absolute bioavailability estimates were 0.255 L/d, 3.60 L, 1.78 L, 0.369 L/d, 0.313 d-1 and 49.2%, respectively, for a subject weighing 70 kg. Terminal half-life was estimated to be approximately 14.6days. Body weight was the primary factor affecting CL and central volume of distribution. CL of guselkumab was similar among patients with PsA, PsO and PPP, but CL in disease populations was 11-17% lower than that in healthy subjects after other covariate effects such as body weight were considered. The population pharmacokinetic analysis indicated that, after other covariate effects were taken into account, patients with PsO, PsA and PPP had similar PK characteristics, with CL in these disease populations being slightly lower than in healthy individuals.