TY - JOUR
T1 - Area under the curve
T2 - Comparing the value of factor VIII replacement therapies in haemophilia A
AU - Persson, Sofie
AU - Berndt, Cecilia
AU - Engstrand, Sara
AU - Trinczek, Annegret
AU - Carlsson, Katarina Steen
AU - Berntorp, Erik
PY - 2022
Y1 - 2022
N2 - Introduction: In factor VIII (FVIII) prophylaxis for haemophilia A, cost comparisons have used price per international unit (IU) based on the once reasonable assumption of equivalent outcome per IU. Now, with several extended half-life (EHL) products available, new outcome-oriented ways to compare products are needed. Area under the curve (AUC) quantifies FVIII levels over time after infusion providing comparable data. Aim: To develop a decision analytical model for making indirect comparisons of FVIII replacement products based on AUC. Methods: A literature search identified 11 crossover studies with relevant pharmacokinetic data. A common comparator FVIII level curve was calculated using pooled data from selected studies. Absolute curves for other products were estimated based on relative differences to the common comparator (% difference vs the anchor). Three scenarios were investigated: (1) Kogenate® versus Kovaltry® and Jivi®; (2) Advate® versus Elocta®, NovoEight®, Kovaltry, Adynovate®, Afstyla®, and ReFacto®; and (3) Jivi versus Elocta, Adynovate, and Kogenate. Sensitivity analyses investigated effects of assay type and dose. Results: In scenario 1, Jivi (+50%) and Kovaltry (+14%) showed larger AUCs versus Kogenate. In scenario 2, EHL products, Elocta and Adynovate, had the largest AUC (+64% and +58%, respectively) versus Advate. Compared with all other products in scenario 3, Jivi had the largest AUC by +13%–28%. Conclusion: This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half-life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head-to-head data.
AB - Introduction: In factor VIII (FVIII) prophylaxis for haemophilia A, cost comparisons have used price per international unit (IU) based on the once reasonable assumption of equivalent outcome per IU. Now, with several extended half-life (EHL) products available, new outcome-oriented ways to compare products are needed. Area under the curve (AUC) quantifies FVIII levels over time after infusion providing comparable data. Aim: To develop a decision analytical model for making indirect comparisons of FVIII replacement products based on AUC. Methods: A literature search identified 11 crossover studies with relevant pharmacokinetic data. A common comparator FVIII level curve was calculated using pooled data from selected studies. Absolute curves for other products were estimated based on relative differences to the common comparator (% difference vs the anchor). Three scenarios were investigated: (1) Kogenate® versus Kovaltry® and Jivi®; (2) Advate® versus Elocta®, NovoEight®, Kovaltry, Adynovate®, Afstyla®, and ReFacto®; and (3) Jivi versus Elocta, Adynovate, and Kogenate. Sensitivity analyses investigated effects of assay type and dose. Results: In scenario 1, Jivi (+50%) and Kovaltry (+14%) showed larger AUCs versus Kogenate. In scenario 2, EHL products, Elocta and Adynovate, had the largest AUC (+64% and +58%, respectively) versus Advate. Compared with all other products in scenario 3, Jivi had the largest AUC by +13%–28%. Conclusion: This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half-life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head-to-head data.
KW - area under the curve
KW - factor VIII
KW - haemophilia A
KW - half-life
KW - health economics
KW - pharmacokinetics
U2 - 10.1111/hae.14691
DO - 10.1111/hae.14691
M3 - Article
C2 - 36445343
AN - SCOPUS:85142938854
JO - Haemophilia
JF - Haemophilia
SN - 1351-8216
ER -