Emicizumab has limited toxicity, although concomitant use of high doses of activated prothrombin complex concentrate increases the thrombotic risk and should be avoided. Moreover, subcutaneous administration and the less frequent dosing interval of once every 1−4 weeks offer dosing convenience, especially for (pediatric) PwHA with difficult venous access. This humanized, immunoglobulin (Ig) G4, bispecific monoclonal antibody (mAb) effectively restores the hemostatic function of missing FVIII by bridging activated factor IX and factor X. Įmicizumab (Hemlibra ®) is the first non-factor replacement product and was approved in 2018 by the US FDA and the European Medicines Agency as prophylaxis for PwHA, both with and without FVIII inhibitors. Additionally, neutralizing antibodies against FVIII (known as inhibitors) develop in 30% of severely affected PwHA, rendering treatment with FVIII products ineffective. This treatment is invasive, requiring intravenous administration every 24–48 h, usually starting before the age of 2 years. However, replacement therapy with FVIII products has some disadvantages. Prophylaxis with plasma-derived and, later, recombinant FVIII products has effectively reduced episodes of bleeding from an annual average of 20−30 to 1−4. The primary goal in the management of these PwHA is to prevent bleeds, preferably through regular coagulation factor replacement therapy (prophylaxis). Without adequate treatment, people with hemophilia A (PwHA) who are severely affected suffer from recurrent bleeds, predominantly in joints, which results in crippling arthropathy, functional limitations and a significantly reduced life expectancy. Hemophilia A is an inherited bleeding disorder caused by an absence or dysfunction of coagulation factor VIII (FVIII). This review supports body weight-based dosing, although individualized monitoring of emicizumab concentrations may allow for more cost-effective dosing. The control of bleeds did not further improve above emicizumab concentrations of 30 µg/mL, potentially enabling lower dosing in a substantial proportion of PwHA. The interindividual variability of trough concentrations was moderate (32%) and was similar across various subgroups, such as FVIII inhibitor status, age group and dosing interval. The 15 included studies reported on data for 140 volunteers and 467 PwHA, including children (0 to <12 years) and adolescents and adults (≥12 years), both with and without factor VIII (FVIII) inhibitors. Data on the study, population, PK and efficacy (annualized bleeding rate of treated bleeds) were extracted and synthesized, and exposure effects modeling was performed using non-linear least squares regression in a maximum effect (E max) model. The EMBASE, Pubmed and CENTRAL databases were systematically searched to November 2020 to identify studies on the PK data of emicizumab in humans. To investigate this assumption, a systematic review on the pharmacokinetics (PK) and associated efficacy of emicizumab in humans was conducted. This assumes a clear dose–concentration–response relationship, with acceptable variability due to factors other than body weight. The approved dosing regimens are based on body weight, without the necessity for laboratory monitoring. Emicizumab is an effective new treatment option for people with hemophilia A (PwHA).
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