Background

The standard-of-care for hemophilia A (HA) involves prophylaxis (PPX) with factor replacement therapies (standard half-life [SHL] and extended half-life [EHL]), or emicizumab (Emi). Despite the availability of these therapies, the clinical burden of HA remains high due to breakthrough bleeding, joint damage, and consequent pain.

Aim

This study aimed to better characterize the usage of additional factor treatment beyond PPX for preventive use before physical activity and for the treatment of patient-reported bleeds in patients with HA (PwHA) treated with SHL, EHL, or Emi.

Methods

This was a retrospective, observational, cohort analysis of moderate to severe PwHA identified through the PicnicHealth database from the US, using electronic health record data linked to electronic patient-reported outcome data. Adult (≥18 years) and pediatric (0−17 years) patients with diagnosis of moderate (1%−5% endogenous FVIII) or severe HA (<1% endogenous FVIII) on routine PPX regimen between March 2022 and March 2024 were included. Patients with evidence of mild HA (6%−50%), any FVIII inhibitor (on index), or treated with efanesoctocog alfa were excluded.

Demographic and clinical characteristics, additional factor treatment patterns and usage beyond PPX (to treat a bleed, before physical activity, before a procedure), patient-reported bleeding events (total bleeds, bleeds by treatment type, bleed causes [injury, spontaneous, procedure], and type [joint, muscle/soft tissue, etc.]), annualized bleed rates (ABRs), routine PPX product class exposure (SHL, EHL, and Emi) were assessed and reported descriptively. Additional factor treatment use did not exclusively mean bleed treatment in this study.

Results

In total, 131 PwHA were included with mean (SD) age of 29 (14) years, 76% were adults, 99% were males, and 87% had severe HA. Patients completed a median (IQR) number of 46 (31−51) Bleeds and Medication surveys during the study period (biweekly). For all patients, median (IQR) study duration (earliest-latest survey) was 1.89 (1.19−1.95) years (SHL PPX: 1.63 [1.04−1.95]; EHL PPX: 1.35 [0.87−1.94]; Emi PPX: 1.83 [1.10−1.95] years).

Of all patients, 78% reported use of factor treatment in addition to PPX at least once during the study period (SHL PPX: 95%, EHL PPX: 83%, and Emi PPX: 65%). Most common reason was ‘to treat a bleed’ (76%), followed by ‘before, during, or after a procedure’ (25%), and ‘before physical exercise’ (21%) to prevent bleeding. Patients on SHL and EHL PPX tend to use the same product class for additional factor treatment (84% and 96%, respectively).

Each patient had completed at least one survey where they reported zero bleeds (during the study period). Around 75% of patients reported one bleed, while 21% reported two bleeds in a single survey. Median (IQR) ABR for all patients, SHL, EHL, and Emi PPX users were 2.0 (0.8−5.6), 3.6 (1.0−7.1), 3.3 (1.2−10.7), and 1.4 (0.0−3.7), respectively. The majority of bleeds were treated (93.4% overall) using additional factor products beyond PPX (SHL PPX: 95.2%; EHL PPX: 96.4%; Emi PPX: 87.2%) with injection or other bleeding medications being most common treatment strategy (89.5% of all bleeds). Emi users were more likely to leave a bleed untreated followed by SHL and EHL PPX users (12.8%, 4.8%, and 3.6%, respectively). Causes of bleeding were majorly attributed to injury/ trauma (53.9% [SHL PPX: 55.4%; EHL PPX: 47.9%; Emi PPX: 59.5%]) followed by spontaneous bleed (43.7% [SHL PPX: 43.2%; EHL PPX: 50%; Emi PPX: 36.2%]). Procedural bleeds were rarely reported (2.4%). Approximately, 61% of overall bleeds were joint bleeds (SHL PPX: 69.8%; EHL PPX: 60.0%; Emi PPX: 50.2%). Muscle/soft tissue bleeds (31%) were also common (SHL PPX: 26.3%; EHL PPX: 31.5%; Emi PPX: 37.0%).

All patients (100%) on SHL >3 times/week (x/wk) regimen used additional factor treatments compared to 94% on ≤3 x/wk regimen. Most patients (88%) on EHL >2 x/wk regimen used additional factor treatments compared to on ≤2 x/wk regimen (77%). Among Emi PPX users, 62% on weekly regimen, 64% on biweekly regimen, and 36% on monthly regimen used additional factor treatment.

Conclusion

The majority of patients with moderate or severe HA on routine PPX use additional factor treatments to treat bleeds, whereas a smaller proportion of patients use additional factor treatment before physical activity or procedures to prevent bleeds.

Disclosures

Roberts:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Weyand:Sanofi: Consultancy, Honoraria, Research Funding; Bayer: Honoraria; Hemab: Consultancy; Novo Nordisk: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Genentech: Honoraria; Octapharma: Honoraria; Biomarin: Honoraria; Pfizer: Research Funding. Reding:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Be Biopharma: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Spark: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kragh:Sobi: Current Employment, Current holder of stock options in a privately-held company. Tsao:Sanofi: Current Employment. Cibelli:PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Hanson:PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Bozkaya:Sanofi: Current Employment. Tardy:Sanofi: Current Employment.

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2024
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