Bleeding Outcomes and Treatment Adherence in Patients with Hemophilia Receiving Standard and Extended Half-Life Factor Replacement Therapy: A Real-World Multinational Survey
Authors: Thakkar Sheena , Wilcox Lisa , Merla Valeria , Kane Anna , Alvir Jose , Pemmaraju Surya , Morton Ella , Garratt-Wheeldon Jade , Ball Nathan , Olsen Stevie , Golden Keisha 
Published: December 2023

Introduction
Hemophilia A (HA) and B (HB) are heritable X-linked disorders characterized by recurrent and extended bleeding episodes resulting from a deficiency of factor VIII and IX, respectively. Management of hemophilia often relies on standard half-life (SHL) and extended half-life (EHL) factor replacement therapy. Effectiveness of these regimens can be affected by level of patient adherence. There are limited data describing the bleeding outcomes and treatment adherence of HA and HB patients receiving SHL or EHL therapy. Here, we aim to describe clinical outcomes, such as bleeding rates and types of bleeds, in a real-world setting among patients receiving either EHL or SHL prophylactic therapy, while also considering perceived treatment adherence.
Methods
Data were drawn from the Adelphi Hemophilia Disease Specific Programme™, a real-world cross-sectional survey of male HA and HB patients conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States of America from February 2020 - May 2021. Hematologists and hematologist-oncologists reported data on consecutively consulting male HA and HB patients, including demographics, treatment history, perceived treatment adherence and bleed history. Patients received treatment prophylactically and had been receiving current treatment for ≥12 months prior to data collection. Patients were grouped by treatment type (SHL or EHL therapy). Analyses were descriptive.
Results
Overall, physicians provided data for 367 patients. Mean (standard deviation; SD) age was 26.9 (14.8) years, 286 patients had HA (66% were receiving SHL and 34% were receiving EHL) and 81 patients had HB (42% were receiving SHL and 58% were receiving EHL). Of the patients with baseline clotting factor data, 58% (n=209) had a baseline activity level of &lt;1%. Table 1 shows treatment data split by hemophilia severity.
Mean (SD) annualized bleed rates (ABR) for HA patients receiving SHL or EHL were 1.2 (1.8) and 1.6 (3.6), respectively. Mean (SD) treatment duration was 7.5 (6.7) years for SHL and 3.0 (2.3) years for EHL. In the 12 months prior to data collection the most common bleed types for SHL (n=96) and EHL (n=49) were joint bleeds (59% and 51%), nosebleeds (26% and 33%) and small cuts (25% and 31%), respectively. Physicians reported the most recent bleed as ‘spontaneous cause’ in 42% and 43% of patients receiving SHL (n=96) and EHL (n=49) treatment, respectively. Physicians perceived that 42% of SHL and 29% of EHL patients were 100% adherent to their prophylaxis regimen and took their treatment on time. Mean (SD) ABR for those with 100% adherence vs &lt;100% adherence in SHL patients was 1.0 (1.3) and 1.3 (2.1), respectively. This was 0.3 (0.7) and 2.1 (4.1) in EHL patients.
Mean (SD) ABR for HB patients receiving SHL or EHL were 1.4 (1.3) and 0.9 (1.1), respectively. Mean (SD) treatment duration was 9.7 (7.7) years for SHL and 3.4 (4.5) years for EHL. In the 12 months prior to data collection the most common bleed types for SHL (n=25) and EHL (n=23) were joint bleeds (52% and 65%) and bruising/skin bleeds (28% and 26%), respectively, and nosebleeds (36% SHL) or microbleeds (22% EHL). Physicians reported the most recent bleed as ‘spontaneous cause’ in 36% and 43% of patients receiving SHL (n=25) and EHL (n=23) treatment, respectively. Physicians perceived that 12% of SHL and 51% of EHL patients were 100% adherent to their prophylaxis regimen and took their treatment on time. Mean (SD) ABR for those with 100% adherence vs &lt;100% adherence in SHL patients was 0.5 (1.0) and 1.5 (1.3), respectively. This was 0.9 (1.1) and 1.0 (1.2) in EHL patients.
Conclusion
We described the bleeding rates of HA and HB patients receiving prophylactic SHL and EHL therapy. Most patients were reported to have more than one bleed a year, and spontaneous bleeds were prevalent despite the use of EHL treatment in HA and HB patients.
Physicians perceived that a high proportion of HA and HB patients were not 100% adherent to either SHL or EHL treatment. Patients who were &lt;100% adherent had numerically higher mean ABRs than those who were 100% adherent. This indicates a need for treatments that maximize adherence and improve upon the current standard of care.