20.500.12556/RUL-136291 Ustekinumab dosing individualization in Crohn's disease guided by a population pharmacokinetic-pharmacodynamic model Ustekinumab is a monoclonal antibody used in Crohn’s disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic–pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. 49.2%, respectively). Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing. ustekinumab inflammatory bowel disease fecal calprotectin pharmacokinetics-pharmacodynamics therapeutic drug monitoring vnetje črevesja terapevtsko spremljanje zdravil fekalni kalprotektin Crohnova bolezen tarčna zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2022-04-22 09:41:20 2022-04-22 09:41:24 2022-09-15 04:13:42 0000-00-00 00:00:00 2021 0 0 16 str. iss. 10, art. 1587 Vol. 13 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.277.3:616.344-002 1999-4923 10.3390/pharmaceutics13101587 78625027 pharmaceutics-13-01587-v2.pdf pharmaceutics-13-01587-v2.pdf 1 E539DCA5F8E73B04072A452578D49659 bce0e93aa3e3e926f4ac0bbf70466849223ced0cf8c735019ce3479a5f54da6b bbf9c845-c20f-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155849 https://www.mdpi.com/1999-4923/13/10/1587 1 8ab4761c-c20f-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155848 Fakulteta za farmacijo Medicinska fakulteta 0 0 0