Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Analysis for Clazakizumab in Patients With End-Stage Kidney Disease Undergoing Dialysis

This study evaluated the pharmacokinetics (PK) and pharmacokinetic–pharmacodynamic (PK–PD) relationship of clazakizumab, an anti–interleukin-6 (IL-6) monoclonal antibody, in patients with end-stage kidney disease receiving dialysis. IL-6–mediated inflammation is a key contributor to cardiovascular disease risk in this population.

Data from a randomized, double-blind, placebo-controlled phase 2b trial were used to develop a population PK model and a longitudinal PK–PD model describing the relationship between clazakizumab exposure and reductions in high-sensitivity C-reactive protein (hs-CRP), a biomarker of systemic inflammation. A two-compartment model with linear elimination adequately characterized drug disposition, while an indirect-response model captured the inhibitory effect of clazakizumab on hs-CRP production.

Model-based simulations demonstrated that all evaluated dosing regimens (2.5 mg, 5 mg, and 10 mg administered every four weeks) produced substantial anti-inflammatory effects, with more than 80 percent of patients predicted to achieve at least an 80 percent reduction in hs-CRP levels.

Overall, these results support the use of model-informed approaches to guide dose selection and optimize therapeutic strategies for clazakizumab in this high-risk patient population.