A recent systematic review provided further support for body weight-based dosing of emicizumab in patients with hemophilia A. The study authors stated, “After body weight-based dosing, emicizumab shows a linear dose-concentration relationship, with moderate interindividual variability.”
Primary pharmacokinetic parameters remained constant with increasing doses of emicizumab. Conversely, the exposure metrics presented a linear dose increase.
The overall weighted interindividual variability of trough concentrations was 32%, which was similar across various subgroups (ie, factor VIII inhibitor status, age group, and dosing interval) and common for therapeutic
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Donners et al also showed that emicizumab concentrations greater than 30 μg/mL did not further improve bleeding control.
To perform this review, the authors selected 15 studies reporting data on 140 healthy volunteers and 467 patients with hemophilia A, both with and without factor VIII inhibitors.
Though supportive of the currently approved dose regimen, the authors highlighted some limitations to this study, including the limited number of studies available and study sizes, among others. They advised, “There is some uncertainty in our findings, particularly in the estimated [annualized bleeding rates] at Ctrough,ss of 30 μg/mL and 50 μg/mL, as a consequence of limited availability of data at lower and higher emicizumab concentrations.”
Donners AAMT, Rademaker CMA, Bevers LAH, et al. Pharmacokinetics and associated efficacy of emicizumab in humans: a systematic review. Clin Pharmacokinet. Published online August 13, 2021. doi:10.1007/s40262-021-01042-w