Switching to extended half-life products may help reduce bleeds
Preventive treatment seen as better than on demand in hemophilia
Switching from on-demand treatment to regular preventive therapy with extended half-life products may mean fewer bleeds, healthier joints, and better quality of life for people with hemophilia.
That’s according to a new analysis of Phase 3 study data from trials involving more than 100 hemophilia patients that spanned a median of at least 3.5 years.
Researchers found, in part, that “joint health outcomes improved in haemophilia A patients” who moved from on-demand to preventive treatment. Scores on a measure of “joints with pain” dropped 29.2% among these individuals; there were insufficient data from hemophilia B patients to draw conclusions.
Moreover, “post switch, bleed protection and health-related quality of life improved across all ages,” the researchers wrote.
The analysis, “Long-Term Outcomes of Prophylaxis with a Recombinant Factor VIII Fc or Recombinant Factor IX Fc in Haemophilia Patients Previously Treated on Demand,” was published in the journal Research and Practice in Thrombosis and Haemostasis.
Fewer doses needed with newer extended half-life products
Hemophilia happens when the body doesn’t have enough clotting factors to help blood to clot and stop bleeding. There are several types of hemophilia, depending on the specific clotting factor that’s defective or is missing.
Replacement therapy is a standard hemophilia treatment that works by replacing the clotting factor patients are missing. In hemophilia A, the most common type of the disorder, that’s factor VIII (FVIII); in hemophilia B, the second most common, it’s factor IX, known as FIX.
When treating hemophilia, clinicians have found that it’s often better for patients to routinely receive replacement therapy — called prophylaxis — to prevent bleeds rather than just treating bleeds when they happen, which is known as on-demand treatment.
Standard products used to require frequent infusions to maintain clotting factors active in the body for a sufficient amount of time. However, with newer extended half-life products, fewer doses are needed because the body takes longer to clear them from circulation.
Now, researchers sought to determine if switching from on-demand to preventive treatment with extended half-life products could help to reduce bleeds, including those occurring in the joints. To that end, the team looked at data from 117 patients who had taken part in several Phase 3 clinical trials.
There were 67 patients with hemophilia A and 50 with hemophilia B. More than 60% came from countries outside Europe and North America. After the switch, none of the patients went back to on-demand treatment.
Hemophilia A patients see better joint health with preventive treatment
Those with hemophilia A had taken part in A-LONG (NCT01181128) and its ASPIRE (NCT01454739) extension study, whereas those with hemophilia B had enrolled in B-LONG (NCT01027364) and its B-YOND (NCT01425723) extension study.
The extended half-life products being tested were efmoroctocog alfa, a lab-made (recombinant) version of FVIII marketed as Elocta in Europe and as Eloctate in the U.S., Canada, and elsewhere, and Alprolix (eftrenonacog alfa), a recombinant FIX protein.
Patients with severe hemophilia A ranged in age from 13 to 64. A total of 51 switched to prophylaxis with efmoroctocog alfa upon entry to A-LONG, while 16 changed to preventive treatment at the start of or during ASPIRE. Over a median of 4.8 years, the median dosing interval increased from 3.5 to 5 days.
After the switch, the overall annualized bleeding rate, calculated as the number of bleeds adjusted to a one-year period, decreased from a median of 30 to 1.5. In the joints, the annualized bleeding rate also decreased, from 21.2 to 1.2. The rate of spontaneous joint bleeds decreased from 14 to 0.4.
Joint health, assessed based on the modified Hemophilia Joint Health Score (mHJHS), also improved, with scores decreasing from a mean of 23.3 to 18.7 points. More than half of the patients (64.6%) experienced improvements in joint health, and nearly 30% saw their number of painful joints decrease.
Health-related quality of life was evaluated using a hemophilia-specific questionnaire for adults, where lower scores indicate better quality of life. After the switch, mean scores decreased from 30.7 to 26.3 points.
A meaningful change, defined as a reduction of at least 7.1 points, was achieved in nearly one-third (32%) of these hemophilia A patients. In sports and leisure and in physical health, a meaningful reduction of 10 points was seen for more than half (51.2% and 54.7%) of the patients.
Bleeding rates drop in hem B patients switching to preventive treatment
Individuals with severe hemophilia B, meanwhile, received prophylaxis with Alprolix for a median of 3.6 years. These patients were ages 12 to 68. Among them, 41 switched from on-demand treatment at the start of B-LONG; another nine moved to preventive treatment at the start of or during B-YOND.
The overall annualized bleeding rate decreased from a median of 24.2 to 2 after the switch. In the joints, the annualized bleeding rate decreased from 16 to 1.1. The rate of spontaneous bleeds into the joints also decreased from 10.5 to 0.4.
Joint health scores decreased by a mean of 1.3 points, but there weren’t enough data to draw firm conclusions about the potential benefits of prophylaxis for joint health in hemophilia B.
Health-related quality of life scores decreased from a mean of 34.2 to 31.1 points, with 27.6% of patients achieving a meaningful reduction in total scores. Most (72%) had a meaningful change in the sports and leisure domain, and over half (52.9%) in physical health.
“This longitudinal subgroup analysis of combined data … provides important insight into how switching patients from on-demand treatment to prophylaxis … benefits their clinical and HRQoL [health-related quality of life] outcomes,” the researchers wrote.
This analysis was funded by Sobi, which markets Elocta, and Sanofi, which markets Eloctate. Sanofi also has acquired Bioverativ Therapeutics, which developed Alprolix.