Clinical Predictors and Prediction Models for rFVIII-Fc Half Life in Real-World People with Severe Hemophilia A

Chia Yau Chang, Shyh Shin Chiou, Te Fu Weng, Pei Chin Lin, Shiue Wei Lai, Chen Hua Tsai, Yen Lin Liu, Jung Tzu Ku, Yu Mei Liao, Jia Ruey Tsai, Shu Hsia Hu, Chao Neng Cheng, Yeu Chin Chen

Research output: Contribution to journalArticlepeer-review


The half life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half life is important for personalized treatment. Eighty-five severe-type PwHA with rFVIII-Fc treatment receiving an evaluation of half life by the Web-Accessible Population Pharmacokinetic (PK) Service—Hemophilia during 2019–2021 were retrospectively enrolled. The 50-patient PK profiles before 2021 were used for analysis and developing prediction models of half life, and the 35-patient PK profiles in 2021 were used for external validation. The patients in the development cohort were aged 8–64, with a median rFVIII-Fc half life of 20.75 h (range, 8.25–41.5 h). By multivariate linear regression analysis, we found two, four, and five predictors of rFVIII-Fc half life for the blood groups non-O, O patients, and overall patients, respectively, including baseline VWF:Ag, BMI, VWF:activity/VWF:Ag ratio, body weight, O blood group, inhibitor history, HCV infection, and hematocrit. The three prediction equations of rFVIII-Fc half life (T) were respectively developed as T for non-O group patients = −0.81 + 0.63 × (BMI, kg/m2) + 6.07 × (baseline VWF:Ag, IU/mL), T for O group patients = −0.68 + 13.30 × (baseline VWF:Ag, IU/mL) + 0.27 × (BW, kg) − 1.17 × (BMI, kg/m2) + 16.02 × (VWF:activity/VWF:Ag ratio), and T for overall patients = −1.76 + 7.24 × (baseline VWF:Ag, IU/mL) − 3.84 × (Inhibitor history) + 2.99 × (HCV infection) − 2.83 × (O blood group) + 0.30 × (Hct, %), which explained 51.97%, 75.17%, and 66.38% of the half life variability, respectively. For external validation, there was a significant correlation between the predicted and observed half lives in the validation cohort. The median half life deviation was +1.53 h, +1.28 h, and +1.79 h for the equations of non-O group, O group, and overall group patients, respectively. In total, eight predictors influencing rFVIII-Fc half life were identified. Prediction equations of rFVIII-Fc half life were developed for the non-O and O blood groups and overall PwHA with a good degree of external validation. The equations could be applied to patients aged 8–64 without the need for PK blood sampling and clinically valuable for personalized therapy.

Original languageEnglish
Article number2207
JournalJournal of Clinical Medicine
Issue number6
Publication statusPublished - 2023 Mar

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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