WFH Vice President, Medical: The future of hemophilia treatment is very promising

Hemophilia treatment has entered an exciting era, with new products making diagnosis and treatment available for a far larger population than ever before, said WHF Vice President, Medical Marijke van den Berg, MD, during her VP Medical Plenary address at the WFH 2016 World Congress.

The session covered a variety of studies in people with severe hemophilia A that demonstrate how early prophylaxis can prevent bleeding and is key for a more positive joint outcome. In these models, prophylaxis replaces episodic therapy, which has been a frequently used hemophilia treatment regimen since the 1970s.

“Modern hemophilia treatment has completely changed the phenotype—but not in countries where early treatment is not available,” she said.

van den Berg cited a very large U.S. study of patients with severe hemophilia A, divided into four birth-date cohorts. Even in the age group born in the 1980s, disability levels were high, she explained, with on average more than five joint bleeds over six months, despite a very high clotting factor consumption.

The large, international Musculoskeletal Function in Hemophilia (MUSFIH) study of children with severe hemophilia A showed that substantial bleeding occurred even with very high factor dosing, van den Berg said. The study also showed that the number of bleeds—but not the dose of episodic treatment—correlates with joint outcome. Understanding this is key, especially since joint function deteriorates after age 12. And signs of loss of joint function are often visible at puberty due to growth spurts.

van den Berg cited a small, randomized study showing that low-dose prophylaxis, rather than episodic treatment, reduces bleeding by 80 percent. Research also shows that early diagnosis is crucial. “Remember, more than 50 percent of those with severe hemophilia A have a negative family history,” she explained.

But when and how do you start prophylaxis? van den Berg said research suggests that the key is to start earlier than age 3 because physical examination scores, which document joint damage, increase when treatment is delayed. Research also shows that low-dose prophylaxis should be administered at least once a week.

There is a correlation between joint scores and dosage of factor replacement. “With a 1,000-1,500 dose, there’s a lot to gain,” stated van den Berg. The good news for people in developing countries, where factor supply is limited, is that data show that lifetime prophylaxis with 1,000 IU/kg is much more effective than episodic treatment. “You can significantly improve outcome with limited factor consumption,” she said.

However, to implement low-dose prophylaxis, comprehensive care centres are crucial, van den Berg said. She recently toured two international hemophilia training centers that are excellent examples of this: the centre in Campinas, Brazil, led by Margareth Castro Ozelo, MD, and the centre in Johannesburg, South Africa, led by Johnny Mahlangu, MD. The Johannesburg centre serves 1,200 patients, with an impressive 35 percent on prophylaxis and home therapy.

Unfortunately, these centres are the exception. Recent data from Africa show that not even 5 percent of people with hemophilia have been diagnosed. “The main reason is because limited or no treatment is available,” van den Berg said.

The WFH Humanitarian Aid Program will substantially address that deficit. From 2016 to 2020, the program plans to provide a predictable supply of 500 million IUs of factor, van den Berg explained. Availability of products will lead to more diagnosis, and that will lead to more training and, in some cases, corrective surgery.

In conclusion, van den Berg said that the evidence shows that only primary prophylaxis can prevent joint disease, and episodic treatment is not an appropriate regimen for severe hemophilia A. When joint bleeds have occurred, signs of arthropathy appear even if very high-dose prophylaxis is given afterwards.

Note: this article was updated by the WFH on September 6, 2016.