PHARMACOKINETIC-GUIDED PROPHYLAXIS FOR PEOPLE WITH HEMOPHILIA A

Abstract

Pharmacokinetic (PK)-guided prophylaxis for people with hemophilia A (PwHA) treatment has been related to fewer bleeding and cost savings have been reported. myPKFiT®is a populational PK tool available for this purpose, developed for α-octocog (Advate®, Takeda) analysis. We evaluated the impact of myPKFiT®-guided prophylaxis in PwHA on replacement costs and bleeding episodes. Men with severe (FVIII < 1%) or moderate (FVIII 1%-5%) HA without inhibitors and treated with Advate®were invited at two Southern Brazilian Hemophilia Treatment Centers. Inclusion criteria involved ≥ 50 exposure days, age 1-65 years, weight 12-120 kg, bleeding-free for ≥ 2 weeks, and last surgical procedure ≥ 6 months. PwHA who developed inhibitor (> 0.6 BU/mL at two time-points) during the study period were excluded. Anthropometric and hemophilia-related data were obtained using a standardized form. PK analysis was performed according to myPKFiT®recommendations, using one-step test. After PK analysis, PwHA were approached to adjust their regimen according to bleeding phenotype, arthropathy, and physical exercise. Replacement regimen and FVIII disposal (from now called consumption) were assessed before and after treatment adjustment. PwHA younger than 15 years were evaluated for 6 months, while those 15 years or older were evaluated for 12 months. Annualized bleeding rate (ABR) was calculated from the reported treated bleeding episodes. FVIII disposal (from now reported as consumption) was adjusted by weight (kg) and monthly. The cost of 1 IU of Advate®was based on the median date of the evaluated periods, which was July/2019. We converted the price in Real into American Dollar, considering the currency at the date that the Brazilian Ministry of Health purchased the product. A total of 37 PwHA were included. In the younger group (n = 20), 75% were severe, and 65% had no hemophiliac arthropathy. Half of these patients were on primary prophylaxis. Two PwHA had a previous history of successful immune tolerance induction. Among the older group (n = 17), 76% were severe, 1 PwHA was treated exclusively on-demand before adjustment, none were on primary prophylaxis, and 12% had no hemophiliac arthropathy. One participant developed inhibitor during the study. Median [interquartile range, IQR] tranged from 9.5 [8.0-10.0] h, among younger individuals, to 10.5 [9.0-11.0] h, among the older ones. Three PwHA from the older group were excluded from the cost analyses: 1 developed inhibitor during follow-up, 1 was treated exclusively on-demand before PK-analysis, and 1 was prescribed plasma-derived FVIII few months after adjustment. From the remaining 34 PwHA, all individuals were advised about behavior and time of infusion, according to their bleeding phenotype, arthropaties, and physical exercise. Among younger PwHA, monthly total FVIII replacement cost increased after PK-based adjustment (p < 0.0001), while reducing costs of episodic therapy (p = 0.05) and increasing costs of prophylaxis (p < 0.0001). Median [IQR] ABR reduced from 3.0 [0.5-10.0] to 1.0 [0.0-2.0]. Among older PwHA, although monthly total and prophylactic costs did not change between the periods, costs of episodic treatment reduced (p = 0.039). ABR did not change either. PK-adjusted prophylaxis was related to increased treatment costs among PwHA < 15 years, but not among individuals ≥ 15 years. Although ABR reduced after adjustment among younger PwHA, no ABR change was evidenced among older participants.