Population-Based Pharmacokinetic Dosing May Benefit Hemophilia A Patients, Study Reports

A population-based pharmacokinetic approach for tailored treatment regimens of hemophilia A patients may contribute to an increase in treatment adherence and a decrease in annual bleeding episodes, a study shows.

The study, “Clinical outcomes in hemophilia A patients undergoing tailoring of prophylaxis based on population-based pharmacokinetic dosing,” was published in Thrombosis Research.

Hemophilia is a genetic blood disorder that affects the body’s ability to form blood clots to prevent excessive bleeding. In hemophilia A, this inability is caused by the lack of a specific clotting protein, called factor VIII (FVIII), due to mutations in the FVIII gene.

Current treatments for hemophilia A include providing the missing FVIII to patients as a prophylaxis, or preventive measure, to avoid spontaneous bleeding episodes. However, determining the appropriate treatment dose based solely on a patient’s weight often leads to either too much or too little medication.

“[For this reason,] it has been recommended that both the dose and infusion frequency should be determined by individual pharmacokinetic (PK) studies, because PK profiles present large variability among individual patients,” the researchers wrote. Pharmacokinetics relate to how a drug is absorbed, distributed, metabolized, and eliminated from the body.

However, a full PK evaluation poses a big burden for patients, especially children and their families, because it requires frequent visits to the clinic to monitor the levels of clotting factors in the patients’ blood and even hospitalizations.

To minimize the difficulties associated with PK evaluation, Shire (now part of Takeda) and a team of researchers from the McMaster University in Canada have each developed their own population-based PK (PopPK) platforms (myPKFiT and WAPPS-Hemo, respectively) to support PK estimation and therapy optimization for patients with hemophilia undergoing prophylactic treatment.

In this study, a group of researchers from the Ogikubo Hospital in Tokyo and their collaborators set out to evaluate how these PopPK strategies influenced patients’ adherence to treatment and the frequency of their bleeding episodes.

The study enrolled 39 patients with hemophilia A who had been receiving prophylactic treatment between October 2014 and October 2017. Individual PK profiles were generated based on the myPKFiT platform for patients treated with Advate and on WAPPS-Hemo for patients treated with other blood-clotting medications. Treatment adherence and the frequency of bleeding episodes were determined based on patients’ diary entries.

Of these 39 patients, 20 required and accepted changes to their treatment regimens — eight increased their treatment doses, two reduced their treatment dose, five reduced treatment frequency, and another five switched from a short half-life to an extended half-life blood-clotting factor medication.

Treatment adherence improved in all patient groups after PopPK, except patients who had to increase their treatment doses because “[this group] originally consisted mostly of patients showing good baseline adherence,” according to the researchers.

In addition, the frequency of bleeding episodes measured by the annualized bleeding rate (ABR) and the annualized joint bleeding rate (AjBR) decreased in all patient groups, especially in those who switched to extended half-life medications and those who were affected by arthropathy (joint disease) at the beginning of the study.

“Our study results suggest that PopPK based tailoring supported changing treatment regimen in nearly half of the patients, and may have contributed to improvement of adherence and reduction of the ABR/AjBR,” the scientists concluded.