Extended half-life factor IX (FIX) products have been designed to prolong the time between clotting factor injections for patients with hemophilia B, but an analysis of real-world data from hemophilia treatment centers suggests that these agents result in poor bleeding control. However, the researchers identified several factors that may predict successful bleed prevention or control in patients receiving these therapies.
Co-author Robert Sidonio Jr., MD, from Children's Healthcare of Atlanta/Emory University, presented the findings at the 2019 Congress of the International Society on Thrombosis and Haemostasis.
"Among the pivotal trials of extended half-life FIX products, FIX plasma trough-activity measurements were widely ranging, with a narrow range of bleeding rates suggesting trough value alone may not predict bleeding," Dr. Sidonio said, explaining the rationale behind this analysis. "FIX has significant distribution to the extravascular space and binding to type IV collagen, which is important in hemostasis but not quantifiable in clinical practice for patients receiving FIX replacement."
Data were collected via an electronic survey distributed to four hemophilia treatment centers in the U.S. Providers were asked if patients with severe hemophilia B who received extended half-life FIX products had experienced either spontaneous/minimally traumatic bleeding events at FIX levels >10% or poorly controlled bleeding events that required more frequent or higher doses of product than anticipated. The survey also reported on patterns of extended half-life FIX product switching.
The four hemophilia treatment centers surveyed treated a total of 71 patients with severe hemophilia B (defined as <1% FIX activity).
Most of these patients (n=55; 77%) received treatment with extended half-life FIX products. Therapies included:
- recombinant FIX albumin fusion protein (rFIX-FP; n=24; 34%)
- recombinant FIX Fc fusion protein (rFIXFc; n=31; 44%)
No patients received glycopegylated recombinant FIX.
A total of 13 patients experienced unexpected spontaneous/minimally traumatic bleeding and poorly controlled bleeding. All 13 patients were treated with rFIX-FP prophylaxis (TABLE).
Looking at patterns of product-switching between different extended half-life products, the investigators found that six patients discontinued these products in favor of switching to a standard half-life product. Five patients switched from rFIX-FP to another extended half-life product, while one patient switched from rFIXFc to another extended half-life product.
"These data demonstrate the importance of real-world monitoring of efficacy of new factor IX products."
â€”Robert Sidonio Jr., MD
"Successful bleed prevention or control in severe hemophilia B may be predicted by the distribution of FIX in circulation and extravascular space and the presence of FIX in tissues at time of injury," the authors observed. "These data demonstrate the importance of real-world monitoring of efficacy of new FIX products and suggest the need for more robust mechanisms to understand the hemostatic performance of products."
The findings of this analysis are limited by the inclusion of only four centers, which may restrict their generalizability to the larger hemophilia B population.
The authors report no relevant conflicts of interest.
Malec LM, Croteau SE, Callaghan M, Sidonio R. Spontaneous bleeding and poor bleeding response with extended half-life factor IX products: a survey of select US hemophilia treatment centers. Abstract OC 70.4. Presented at the International Society of Thrombosis and Haemostasis 2019 Congress, July 10, 2019; Melbourne, Australia.