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RESEARCH

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Blood Res (2024) 59:29

Published online August 29, 2024

https://doi.org/10.1007/s44313-024-00023-9

© The Korean Society of Hematology

Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review

Young-Shil Park1 , Ki-Young Yoo2 , Sang Kyu Park3 , Taiju Hwang4 , Aeran Jung5 and Eun Jin Choi6*

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1 Department of Pediatrics, Kyung Hee University Hospital, Gangdong, Seoul, Republic of Korea
2 Korea Hemophilia Foundation Clinic, Seoul, Republic of Korea
3 Korea Hemophilia Foundation Clinic, Busan, Republic of Korea
4 Korea Hemophilia Foundation Clinic, Gwangju, Republic of Korea
5 Medical Affairs, Takeda Pharmaceuticals Korea Co., Ltd, Seoul, Republic of Korea
6 Department of Pediatrics, Daegu Catholic University Medical Center, 33 Duryugongwon‑Ro 17‑Gil, Nam‑Gu, Daegu 42472, Republic of Korea

Correspondence to : Eun Jin Choi
ejchoi2@cu.ac.kr

Received: March 26, 2024; Accepted: June 21, 2024

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

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Purpose This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population.
Methods We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases.
Results The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small.
Conclusion This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Keywords Hemophilia A, FVIII, Pharmacokinetics, Prophylaxis, Korean

Article

RESEARCH

Blood Res 2024; 59():

Published online August 29, 2024 https://doi.org/10.1007/s44313-024-00023-9

Copyright © The Korean Society of Hematology.

Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review

Young-Shil Park1 , Ki-Young Yoo2 , Sang Kyu Park3 , Taiju Hwang4 , Aeran Jung5 and Eun Jin Choi6*

1 Department of Pediatrics, Kyung Hee University Hospital, Gangdong, Seoul, Republic of Korea
2 Korea Hemophilia Foundation Clinic, Seoul, Republic of Korea
3 Korea Hemophilia Foundation Clinic, Busan, Republic of Korea
4 Korea Hemophilia Foundation Clinic, Gwangju, Republic of Korea
5 Medical Affairs, Takeda Pharmaceuticals Korea Co., Ltd, Seoul, Republic of Korea
6 Department of Pediatrics, Daegu Catholic University Medical Center, 33 Duryugongwon‑Ro 17‑Gil, Nam‑Gu, Daegu 42472, Republic of Korea

Correspondence to:Eun Jin Choi
ejchoi2@cu.ac.kr

Received: March 26, 2024; Accepted: June 21, 2024

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

Purpose This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population.
Methods We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases.
Results The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small.
Conclusion This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Keywords: Hemophilia A, FVIII, Pharmacokinetics, Prophylaxis, Korean

Fig 1.

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Figure 1.Distribution of dose and frequency by quartiles of time to 1%. A Dose (IU/kg) of octocog alfa; (B) dose of rurioctocog alfa pegol; (C) frequency (injections per week) of octocog alfa; and (D) frequency of rurioctocog alfa pegol. The box in the plot represents the interquartile range (IQR), and the points extending from the box represent values that are 1.5 times greater than the IQR from the median value. R2 was calculated using a simple linear regression
Blood Research 2024; 59: https://doi.org/10.1007/s44313-024-00023-9

Fig 2.

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Figure 2.Distribution of dose and frequency by quartiles of half-life. A Dose (IU/kg) of octocog alfa; (B) dose of rurioctocog alfa pegol; (C) frequency (injections per week) of octocog alfa; and (D) frequency of rurioctocog alfa pegol. The box in the plot represents the interquartile range (IQR), and the points extending from the box represent values that are 1.5 times greater than the IQR from the median value. R2 was calculated using a simple linear regression
Blood Research 2024; 59: https://doi.org/10.1007/s44313-024-00023-9

Table 1 . Demographic data.

VariablesOctocog alfa (N = 48)Rurioctocog alfa pegol (N = 81)P-value
Mean ± SD or N (%)Mean ± SD or N (%)
Sex
Male47(97.92)81(100.00)0.3721
Female1(2.08)-
Age, years23.21 ± 10.6627.60 ± 10.040.0779
Height, cm162.60 ± 23.09172.66 ± 5.230.0898
Weight, kg59.64 ± 23.3673.30 ± 12.470.0035
BMI, kg/m223.29 ± 4.2724.78 ± 3.780.0545
< 18.57(14.58)2(2.47)0.0369
18.5–22.913(27.08)21(25.93)
23.0–24.95(10.42)18(22.22)
≥ 25.017(35.42)31(38.27)
Blood type
A15(31.25)27(33.33)0.2370
B8(16.67)21(25.93)
AB3(6.25)5(6.17)
O15(31.25)12(14.81)
Unknown7(14.58)16(19.75)
FVIII level (Baseline)
Severe (< 1 IU/dL)41(85.42)70(86.42)0.8737
Moderate (≥ 1– < 5 IU/dL)7(14.58)11(13.58)

BMI Body mass index, SD Standard deviation.

Table 2 . Medical history and treatment.

VariablesOctocog alfa (N = 48)Rurioctocog alfa pegol (N = 81)P-value
Mean ± SD or N (%)Mean ± SD or N (%)
Medical history
FVIII inhibitor history
Yes (≥ 0.6 BU)6(12.50)5(6.17)0.8737
No (< 0.6 BU)42(87.50)76(93.83)
ITI history0.4986
Yes5(10.42)5(6.17)
No43(89.58)76(93.83)
ITI Completion
Yes5(10.42)5(6.17)
ITI Result-
Complete response5(10.42)5(6.17)
Partial Response/Fail--
Treatment information
FVIII treatment regimen at the time of PK test0.2811
Prophylaxis40(83.33)72(88.89)
On-demand4(8.33)2(2.47)
Prophylaxis + On-demand2(4.17)6(7.41)
Other1(2.08)-
Unknown1(2.08)1(1.23)
Dose, IU/kg29.09 ± 4.6828.81 ± 4.040.1842
Frequency, Times per week2.98 ± 1.502.20 ± 0.80< 0.0001

ITI Immune tolerance induction, SD Standard deviation.

Table 3 . PK profiles of octocog alfa and rurioctocog alfa pegol.

Octocog alfa (N = 48)Rurioctocog alfa pegol (N = 81)Difference (%)aP-value
Median (min, max)Median (min, max)
Half-life (h)9.90 (6.30, 15.20)15.30 (10.40, 23.90)154.06< 0.0001
Time to 1% (h)53.00 (27.00, 88.00)94.00 (63.00, 150.00)176.37< 0.0001
Clearance (dL/h/kg)0.04 (0.02, 0.08)0.02 (0.01, 0.04)40.00< 0.0001

a Difference (%) = (values of rurioctocog alfa pegol/octocog alfa)*100.

Table 4 . Regression analysis of PK profile and patient variables.

VariablesParameterOctocog alfaRurioctocog alfa pegol
nEstimateP-valuenEstimateP-value
Half-life (h)Age480.106< 0.0001810.0130.6850
BMI420.1000.146072-0.0530.5490
vWF:Ag60.0450.1026180.0460.0002
Time to 1% (h)Age480.5890.0002810.1440.4800
BMI420.5670.2166720.1790.7580
vWF:Ag60.3310.0528180.311< 0.0001
Clearance (dL/h/kg)Age48-0.0010.0002810.0010.9200
BMI42-0.0010.131072-0.0010.0090
vWF:Ag6-0.00020.1859180.00000.0052

BMI Body mass index, vWF Ag, von Willebrand factor antigen.

Table 5 . PK profile of each product according to age, blood type, inhibitor history, and BMI classification.

VariablesOctocog alfa (N = 48)Rurioctocog alfa pegol (N = 81)
nMedian (min, max)P-valuenMedian (min, max)P-value
Age
Half-life (h)
< 6 years38.30 (6.30, 10.60)0.0941--
≥ 6– < 12 years59.21 (7.20, 9.50)--
≥ 12–18 years79.70 (7.80, 11.30)1114.80 (12.10, 19.10)0.6807
≥ 18 years3310.30 (6.40, 15.20)7015.40 (10.40, 23.90)
Time to 1% (h)
< 6 years345.00 (34.00, 58.00)0.4220--
≥ 6– < 12 years551.00 (38.00, 54.00)--
≥ 12– < 18 years752.00 (38.00, 62.00)1188.00 (67.00, 108.00)0.3315
≥ 18 years3354.00 (27.00, 88.00)7095.00 (63.00, 150.00)
Clearance (dL/h/kg)
< 6 years30.05 (0.04, 0.07)0.0829--
≥ 6– < 12 years50.05 (0.05, 0.06)--
≥ 12– < 18 years70.05 (0.04, 0.06)110.02 (0.02, 0.03)0.1015
≥ 18 years330.04 (0.02, 0.08)700.02 (0.01, 0.04)
Blood type
Half-life (h)
O158.30 (6.40, 10.60)< 0.00011212.65 (10.40, 18.00)< 0.0001
Non-O2610.6 (6.30, 15.20)5315.70 (10.40, 23.90)
Time to 1% (h)
O1542.00 (27.00, 56.00)< 0.00011275.00 (63.00, 112.00)< 0.0001
Non-O2657.00 (34.00, 88.00)5396.00 (66.00, 150.00)
Clearance (dL/h/kg)
O150.06 (0.04, 0.08)< 0.0001120.03 (0.02, 0.04)< 0.0001
Non-O260.04 (0.02, 0.07)530.02 (0.01, 0.02)
Inhibitor history
Half-life (h)
Yes (≥ 0.6 BU)68.50 (6.30, 13.90)0.2082515.40 (10.40, 15.60)0.1469
No (< 0.6 BU)429.95 (6.40, 15.20)7615.30 (10.40, 23.90)
Time to 1% (h)
Yes (≥ 0.6 BU)641.00 (34.00, 77.00)0.2355594.00 (66.00, 95.00)0.2025
No (< 0.6 BU)4253.00 (27.00, 88.00)7693.50 (63.00, 150.00)
Clearance (dL/h/kg)
Yes (≥ 0.6 BU)60.05 (0.03, 0.07)0.142350.02 (0.02, 0.02)0.6368
No (< 0.6 BU)420.04 (0.02, 0.08)760.02 (0.01, 0.04)
BMI (kg/m2)
Half-life (h)
< 18.578.40 (6.30, 11.70)0.2139214.65 (10.50, 22.50)0.8583
18.5–22.9139.90 (7.80, 11.90)2115.40 (11.90, 19.20)
23.0–24.9510.60 (8.90, 15.20)1814.45 (10.40, 23.90)
≥ 25.01710.30 (6.40, 13.40)3115.40 (10.40, 23.90)
Time to 1% (h)
< 18.5748.00 (34.00, 64.00)0.2882284.00 (63.00, 137.00)0.5681
18.5–22.91353.00 (39.00, 64.00)2191.00 (70.00, 117.00)
23.0–24.9555.00 (46.00, 88.00)1888.50 (64.00, 150.00)
≥ 25.01754.00 (27.00, 79.00)3195.00 (64.00, 150.00)
Clearance (dL/h/kg)
< 18.570.05 (0.04, 0.07)0.303920.02 (0.02, 0.03)0.0029
18.5–22.9130.05 (0.03, 0.06)210.02 (0.02, 0.04)
23.0–24.950.04 (0.02, 0.05)180.02 (0.01, 0.03)
≥ 25.0170.04 (0.03, 0.08)310.02 (0.01, 0.03)

BMI Body mass index.

Table 6 . BMI classifications (adults).

[unit: kg/m2]UnderweightNormalOverweightObesity
Korea [16]< 18.518.5–22.923.0–24.9≥ 25.0
WHO [17]< 18.518.5–24.925.0–29.9≥ 30.0
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