Personalized prophylaxis becomes new standard in hemophilia treatment

After experiencing many dramatic treatment turning points, the latest global trend in hemophilia treatment is shifting toward personalizing prophylaxis for each hemophilia patient.

The reasons for personalizing prophylaxis for hemophilia patients, who are at risk of spontaneous bleeding due to a deficiency of factors 8 and 9, are pretty straightforward.

“Since the pharmacokinetics of drugs are different for each hemophilia patient, the peak concentration may be slightly different when the same dose of drug is infused, and the rate at which it is washed out of the body may be faster,” said Professor Shim Ye-jee of the Department of Pediatrics at Kyungpook National University Hospital during a health talk show titled “Overcoming Hemophilia Together: Integrated Solutions for Treatment and Communication,” sponsored by the Korea Hemophilia Association and Korea Healthlog, the sister paper of Korea Biomedical Review last Sunday.

For this reason, Professor Shim said personalized treatment is the most recommended preventive therapy.

Notably, for “moderate or severe hemophilia” patients with less than 5 percent of 8-9 blood coagulation factor activity, the factor activity that triggers spontaneous bleeding may vary from patient to patient. For this reason, personalized preventive treatment has become a major trend. In Korea, patients who have too short a half-life for drugs or a factor activity of 1 percent can receive personalized treatment by submitting the results of pharmacokinetics (PK) profiles to the Health Insurance Review and Assessment Service (HIRA).

“It is most recommended that each hemophilia patient undergoes a PK profile test about once a year to measure how much the blood clotting factor rises when given and falls within a few hours so that personalized treatment can be provided,” Professor Shim said, emphasizing the importance of thorough treatment and management of hemophilia compared to other bleeding diseases, as it can also cause recurrent joint bleeding and spontaneous bleeding in the cardiovascular system, such as brain hemorrhage.

“Recent studies have shown that it is much more important for people with hemophilia to maintain a certain level of factor 8-9 during the day, rather than just giving factors 8-9 when needed, so that they can go about their daily lives just like people without hemophilia,” Shim said. “The recent updates to the World Federation of Hemophilia (WFH)'s hemophilia treatment guidelines have changed the definition of primary treatment goals and prophylaxis regimens.”

The guidelines have previously set a goal of maintaining a minimum clotting factor concentration of 1 percent, but that goal has recently been raised.

“Recently, the target has been raised again to 3-5 percent or higher, and many clinicians are recommending higher factor levels because they see that patients are at risk of bleeding, and the higher the factor level, the less risk of bleeding in everyday life, and especially if the trough factor level can be maintained at 15 percent or higher, the more spontaneous bleeding that occurs without trauma can be reduced,” Professor Shim explained.

In addition, the earlier, the better, but the mainstream of hemophilia prophylaxis has been intravenous medications administered two to three times a week, making it challenging to apply prophylaxis to children who have difficulty finding a vein to insert a needle. However, recent advances in treatment technology have made it possible to overcome the challenges of early prophylaxis in pediatric patients with hemophilia, according to Shim.

“Guideline recommendations show that early initiation of prophylaxis is very positive for long-term prognosis, but the difficulty of intravenous administration made it difficult to initiate prophylaxis (at a younger age),” Shim explained, adding that the advent of subcutaneous drug options, including Hemlibra, a non-clotting factor agent, has made early treatment easier for children.

Another advantage of non-clotting factor agents is that they can be used to maintain normal clotting factor activity levels of 9-15 percent.

“Non-clotting factor agents can maintain the activity of clotting factors around 9 to 15 percent of normal,” Shim said. "Hemlibra has a PK profile that is very insensitive to peaks and troughs and stays around 9-15 percent. It's on target for being physically active and maintaining joint health."

So, what difference does prophylaxis make to a person with hemophilia?

“When we look at the outcomes of prophylaxis, we find that people with hemophilia have less pain, have a more active social life, are less likely to be hospitalized, have better mental health, and are less likely to be absent from work or school,” Shim said.

Some patients benefit more significantly than others from prophylaxis.

“Some data show that prophylaxis is better for patients with severe bleeding episodes, even if they don't have severe hemophilia, especially those who want to exercise and live an active life, those who have worsening arthropathy and need to stop having arthropathy, and those who have difficulty managing bleeding with medical treatment alone,” Professor Shim said.

Physical activity is essential, along with maintaining a minimum clotting factor level of 15% or higher

Physical activity, once considered taboo, is now seen as beneficial to the health of people with hemophilia. Maintaining a trough level of factor 8-9 of at least 15 percent can significantly reduce the risk of spontaneous bleeding. The WFH recommends regular physical activity for people with hemophilia to maintain bone health, strengthen muscles, and improve health and positive self-esteem.

“Data show that regular physical activity improves joint stability and function and reduces acute bleeding-related complications in people with hemophilia,” Shim said. “Physical activity is significant, along with maintaining a blood clotting factor level of at least 15 percent for ideal health.”

For “healthy hemophiliacs” with well-maintained blood clotting factor levels, Professor Shim recommended organized exercise once or twice a week, strength training, such as yoga or Pilates, three to four times a week, aerobic exercise, including walking, swimming, or cycling, for at least 20 minutes four to five times a week, and physical activity like walking or climbing stairs instead of driving every day.

"The current treatment goals for hemophilia are tailored prevention, individualized management, and treatment based on individual PK," Professor Shim said, stressing that hemophiliacs should also work to maintain the health of the muscles surrounding the joints to keep them healthy.