How Does Emicizumab Work in Obese Adults with Hemophilia A?
What is the annual bleeding rate and minimum concentration of emicizumab in obese adults with hemophilia A compared to non-obese individuals? Answers were sought by the authors of a pooled post hoc analysis of the HAVEN 1, 3, and 4 studies, the results of which were presented in the poster section of the 2021 ISTH virtual congress. Based on modeling, body weight appears to be an important predictor of emicizumab pharmacokinetics.
Analyzed Data
Before the HAVEN program began, informed consent from patients and approval from the ethics committee were obtained. Inclusion criteria for the analysis were age ≥ 18 years, presence or absence of factor VIII (FVIII) inhibitor, use of emicizumab for ≥ 24 weeks, and knowledge of baseline BMI. Annual bleeding rate (ABR) during the study and in 24-week intervals until dose titration, and mean minimum plasma concentrations of emicizumab were analyzed.
Findings
Data were analyzed from 260 adult patients with hemophilia A. Of them, 44 (17%) had a BMI ≥ 30 kg/m2 and 216 (83%) had a BMI < 30 kg/m2. Emicizumab exposure in the BMI ≥ 30 kg/m2 group was 94.29 patient-years, and in the BMI < 30 kg/m2 group it was 522.97 patient-years.
Adjusted ABR during the study was similar between the two groups (1.48 for patients with BMI ≥ 30 kg/m2 vs. 1.40 for those with BMI < 30 kg/m2). ABR remained consistent over time in both groups.
Effective minimum drug concentrations were maintained in both groups regardless of dosing regimen (achieving > 30 µg/ml). At week 5 post-loading phase, the mean minimum concentration of emicizumab when administered weekly was 51.47 µg/ml in the BMI ≥ 30 kg/m2 arm (n = 27) vs. 53.21 µg/ml in the BMI < 30 kg/m2 arm (n = 137).
Conclusion
Minimum effective concentrations of emicizumab were maintained in the HAVEN 1, 3, and 4 studies in patients with hemophilia A, regardless of whether they were obese or had a BMI not indicative of obesity. The annual rate of treated bleeding episodes was similar in both groups. These data suggest that body weight does not have a significant impact on the effectiveness of this drug, regardless of its dosage. The therapy remains effective and well-tolerated, and the dosing regimen is flexible even in obese patients.
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Source: Recht M., Mahlangu J., Minhas M. et al. Emicizumab in obese adults with hemophilia A – pooled data from three phase III studies (HAVEN 1, 3 and 4). ISTH Congress 2021. Res Pract Thromb Haemost 2021; 5 (Suppl. 1): PB0495. Available at: https://abstracts.isth.org/abstract/emicizumab-in-obese-adults-with-hemophilia-a-pooled-data-from-three-phase-iii-studies-haven-1-3-and-4
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