Comparison of single subject and population-based pharmacokinetics for optimizing prophylaxis with simoctocog alfa in patients with haemophilia A

Research output: Contribution to journalArticle

Standard

Comparison of single subject and population-based pharmacokinetics for optimizing prophylaxis with simoctocog alfa in patients with haemophilia A. / Astermark, Jan; Olsson, Anna; Chelle, Pierre; Täckström, Kinga; Walger, Maria; Magnusson, Maria; Iorio, Alfonso.

In: Haemophilia, 09.05.2021.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Astermark, Jan ; Olsson, Anna ; Chelle, Pierre ; Täckström, Kinga ; Walger, Maria ; Magnusson, Maria ; Iorio, Alfonso. / Comparison of single subject and population-based pharmacokinetics for optimizing prophylaxis with simoctocog alfa in patients with haemophilia A. In: Haemophilia. 2021.

RIS

TY - JOUR

T1 - Comparison of single subject and population-based pharmacokinetics for optimizing prophylaxis with simoctocog alfa in patients with haemophilia A

AU - Astermark, Jan

AU - Olsson, Anna

AU - Chelle, Pierre

AU - Täckström, Kinga

AU - Walger, Maria

AU - Magnusson, Maria

AU - Iorio, Alfonso

PY - 2021/5/9

Y1 - 2021/5/9

N2 - Introduction: The use of pharmacokinetic assessment for optimal prophylactic dosing of factor concentrates in haemophilia has gained increasing enthusiasm over the last decade. However, blood sampling on several occasions is burdensome and limited sampling using population-based PK is appealing. Aim: To compare the pharmacokinetics and dosing recommendations for prophylaxis using six-point single subject versus population-based method (WAPPS-Hemo) for simoctocog alfa (Nuwiq®). Methods: Twelve adult patients with severe haemophilia A received a factor VIII (FVIII) dose of ≈50 IU/kg, and the activity was measured pre-infusion and at 30 min, 6, 9, 24 and 48 h post-infusion. Half-life (t1/2), weight-normalized AUC and time to troughs of 5%, 3% and 1% were calculated. The correlation between the PK algorithms was assessed using intraclass correlations (ICC) and dosing estimations were provided. Results: WAPPS-Hemo yielded a slightly longer mean t1/2, but the overall correlation between the methods was good (ICC ≥0.79) The time to troughs of 5%, 3% and 1% showed ICCs ≥0.86. For all variables, the most converging limited time point was 6+48 h. Additional time points did not improve the correlation. Despite similar pharmacokinetics, the mean estimated dose for a specific trough level varied from 60% less to 20% more using the population-based approach. The time to 1% and the corresponding dose was sensitive to the baseline assumption. Conclusion: Our data support the use of population-based PK for patients on simoctocog alfa prophylaxis but also indicates differences, stressing the importance of the sampling scheme and monitoring actual FVIII levels achieved.

AB - Introduction: The use of pharmacokinetic assessment for optimal prophylactic dosing of factor concentrates in haemophilia has gained increasing enthusiasm over the last decade. However, blood sampling on several occasions is burdensome and limited sampling using population-based PK is appealing. Aim: To compare the pharmacokinetics and dosing recommendations for prophylaxis using six-point single subject versus population-based method (WAPPS-Hemo) for simoctocog alfa (Nuwiq®). Methods: Twelve adult patients with severe haemophilia A received a factor VIII (FVIII) dose of ≈50 IU/kg, and the activity was measured pre-infusion and at 30 min, 6, 9, 24 and 48 h post-infusion. Half-life (t1/2), weight-normalized AUC and time to troughs of 5%, 3% and 1% were calculated. The correlation between the PK algorithms was assessed using intraclass correlations (ICC) and dosing estimations were provided. Results: WAPPS-Hemo yielded a slightly longer mean t1/2, but the overall correlation between the methods was good (ICC ≥0.79) The time to troughs of 5%, 3% and 1% showed ICCs ≥0.86. For all variables, the most converging limited time point was 6+48 h. Additional time points did not improve the correlation. Despite similar pharmacokinetics, the mean estimated dose for a specific trough level varied from 60% less to 20% more using the population-based approach. The time to 1% and the corresponding dose was sensitive to the baseline assumption. Conclusion: Our data support the use of population-based PK for patients on simoctocog alfa prophylaxis but also indicates differences, stressing the importance of the sampling scheme and monitoring actual FVIII levels achieved.

KW - haemophilia

KW - nuwiq

KW - pharmacokinetics

KW - population

KW - prophylaxis

KW - simoctocog alfa

UR - http://www.scopus.com/inward/record.url?scp=85105455165&partnerID=8YFLogxK

U2 - 10.1111/hae.14329

DO - 10.1111/hae.14329

M3 - Article

C2 - 33966319

AN - SCOPUS:85105455165

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

ER -