New Methods Can Help Identify Best Preventive Regimen for Children with Hemophilia A, Study Says

Researchers are creating a free web-based calculator that will help physicians determine the best patient-specific preventive regimens for children with hemophilia, according to a recent study.

The tool is based on newly developed methods that identified key features of an effective preventive regimen. This includes giving Factor VIII (FVIII) injections of equal doses at equal intervals, although levels of physical activity were found to be a determining factor in finding the best dosing regimen.

The study, “Optimization of prophylaxis for hemophilia A,” appeared in the journal PLOS ONE.

Hemophilia A results from missing or defective FVIII, a clotting protein. Prophylactic, or preventive, FVIII injections reduce the frequency of bleeds and slow the development of joint damage in children with a severe form of the disease. Other strategies consist of maintaining the body’s own concentration of FVIII above 1 IU/dL, which is also important in reducing the incidence of bleeds.

Scientists have been discussing strategies to create optimal personalized preventive regimens, but a systematic study to establish which regimen is best suited for each individual hadn’t been done yet, the researchers said.

As a result, the research team conducted a study to identify new analytical and numerical methods to help design person-specific, globally optimal preventive regimens for children with hemophilia A.

The study required extensive study of pharmacokinetics, or how a drug behaves inside the body, an analysis that accounted for changes in blood FVIII concentrations over time with the different treatment regimens.

Results revealed that giving injections of equal doses at equal intervals maximized the time that FVIII concentration remained above the 1 IU/dL threshold. Specifically, “prophylaxis was optimal, in the sense of maximising time above threshold, when the second and third injections were given 56 and 112 hours after the first,” the investigators wrote.

This protocol enables maintenance of blood FVIII concentration above the desired level for a total of 168 hours per week. Other dosing intervals achieved this goal, with equal doses and equal intervals being common factors to all.

An optimal preventive regimen also depends on the child’s physical activity. Results show that for what the researchers call “very active” children, any regimen with a total dose of 90 IU/kg given in up to three weekly injections of equal doses confers a similar prevention of bleeds. Data shows that the patterns of physical activity are also important, as the preventive regimen of “very active” children differs from those who are considered “inactive” or “weekend active.” For example, “weekend active” children are best treated with unequal doses of FVIII, two on the weekend and one on a weekday afternoon.

“Perhaps the most important finding from this study is that the prophylaxis regimens that minimize risk of bleeds may be very different to prophylaxis regimens that maximize pharmacokinetic parameters,” the investigators wrote. These pharmacokinetic parameters refer to the time above a threshold FVIII concentration and the lowest FVIII concentration.

The study provides methods to “maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds,” the researchers wrote.

Based on these methods, researchers are now creating a web-based calculator, called MOrPH, that will be free for physicians’ use and will help them make the necessary calculations to determine optimal preventive regimens for each patient.