Abstract Number: PB0513
Meeting: ISTH 2021 Congress
Background: Pharmacokinetics (PK) of extended half-life products is important for individualized prophylaxis of patients with hemophilia A (PwHA). Great variation in real world of rFVIII-Fc half life have been reported in some developed countries.
Aims: We aimed to develop a predictive model of rFVIII-Fc half life in PwHA.
Methods: Totally 50 PwHA on rFVIII-Fc replacement therapy were enrolled from two hemophilia centers. Clinical data, including age, BW, BMI, Hct, ABO blood group, von Willebrand factor (VWF) levels, inhibitor history, HCV status, and individual PKs calculated by WAPPS-hemo were collected from charts reviewed retrospectively. Linear regression by SAS software was used for searching out predictors of rFVIII-Fc half life from all the covariates.
Results: The mean age was 34.6±15.9 y/o (8－64). The mean Hct was 43.8% (29.9－52.6%). Twenty-one patients were blood-group O, and 29 were non-O. Mean VWF:Ag was 112.5±54.1% (50－294.7%). Mean ratio of VWF:activity or Rco over VWF:Ag (defined as VWF:Quality) was 0.93 (0.67－1.21). For PwHA of non-O group and O group, rFVIII-Fc half lives were 22.83±6.46h and 16.26±4.61h, respectively (p<0.001***) and VWF:Ag levels were 132.10±63.72% and 86.93±19.30%, respectively (p<0.01**). After multivariate linear regression analysis, for all blood groups, VWF:Ag, HCV infection, and Hct were identified as positive predictors and O blood group and inhibitor history as negative predictors of rFVIII-Fc half life. For non-O group, BMI was an extra positive predictor. For O group, BW was an extra positive predictor and VWF:Quality was an extra negative predictor. Three predictive equations were developed (Table 1), explaining 51.97%,75.17%, and 66.38% of all variability in rFVIII-Fc half-life for PwHA of non-O group, O group, and all blood groups, respectively.
|Table 1. Predictive equations of rFVIII-Fc half life by multivariate linear regression analysis|
|Blood groups||Predictive equation of rFVIII-Fc half life|
|1) For hemophilia A patients with non-O blood group||– 0.81245 + 0.62874 * (BMI) + 0.06065 * (VWF:Ag%)|
|2) For hemophilia A patients O blood group||– 0.68276 + 0.13301 * (VWF:Ag%) + 0.26831 * (BW) – 1.16586 * (BMI) +16.02271 * (VWF:Quality†)|
|3) For hemophilia A patients all blood groups||– 1.75958 + 0.07243 * (VWF:Ag%) – 3.84423 * (Inhibitor history‡) + 2.98525 * (HCV infection‡) – 2.82626 * (O blood group#) + 0.30393 * (Hct%)|
|†, VWF:Quality is defined as ratio of VWF:activity or Rco over VWF:Ag; ‡, positive is 1 and negative=0; #, O group is 1 and non-O group is 0.|
Several predictors of rFVIII-Fc half life were searched out and prediction models were well developed. We believe they will be useful for physician to individualize prophylaxis of PwHA on rFVIII-Fc.
To cite this abstract in AMA style:Chang C-, Lai S-, Liu Y-, Tsai J-, Tsai C-, Cheng C-, Hu S-, Ku J-, Chen Y-. Developing Predictive Models of rFVIII-Fc Half Life for Personalized Prophylaxis in Patients with Hemophilia A [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/developing-predictive-models-of-rfviii-fc-half-life-for-personalized-prophylaxis-in-patients-with-hemophilia-a/. Accessed September 23, 2021.
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