Population pharmacokinetic-pharmacodynamic model for secukinumab in patients with psoriasis

Psoriasis is a chronic immune-mediated inflammatory disease for which biologic therapies have substantially improved clinical outcomes; however, long-term treatment costs and potential safety concerns highlight the need for dose optimization. Model-informed precision dosing may support individualized biologic use but requires reliable pharmacokinetic/pharmacodynamic models based on patient-level data. This study aimed to characterize the pharmacokinetic/pharmacodynamic relationship of secukinumab in a real-world adult psoriasis population to support the future implementation of model-informed precision dosing. A joint population pharmacokinetic/pharmacodynamic model was developed using 244 serum concentration measurements and 262 PASI scores from 61 patients from the BeNeBio (NCT04340076) and BIOLOPTIM (NCT04080661) studies. Secukinumab pharmacokinetics were best described by a 1-compartment model with first-order absorption and elimination, with allometric scaling on clearance and volume of distribution. The PASI response was characterized using an indirect response maximal drug effect turnover model. Simulations identified week 24 trough concentration targets of 14.5 μg/ml and 35.5 μg/ml, which were associated with a 90% probability of achieving PASI ≤ 2 and PASI ≤ 1, respectively. These results characterize secukinumab exposure-response relationships in a real-world setting and provide clinically plausible concentration targets. The model provides a foundation for the future evaluation of model-informed precision dosing in biologic dosing for psoriasis.