111 Systematic review on PK of emicizumab Figure 2. Trough concentrations of emicizumab with variability across various subgroups in PwHA. The weighted variability (%CV) of the Ctrough,ss of emicizumab was similar across FVIII inhibitor status and across various dosing intervals, whereas children had slightly less variability than adults/adolescents. The overall weighted %CV was 32%. Data from PwHA (n = 469) receiving multiple dose regimens were included (see ‘a’ for 15 study subgroups in Supplemental Table ST2). Concentration−response relationship Table 3 shows the relevant parameter estimates from the published population PK models on emicizumab. The model by Yoneyama et al. was based on PK data from the phase I and I/II studies to establish the dosing regimens, and the model by Retout et al. was based on the long-term phase I/II and the phase III HAVEN 1−4 studies [24, 36]. The total PK inter-individual variability (approximately 60% [36]) could be explained primarily by the covariates body weight (BW), neutralizing anti-drug antibodies (ADA) against emicizumab, age >30 years and, to a lesser extent, abnormal albumin (ALB) levels and African race. 6
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