Multiyear, Real-World, Retrospective Cohort Study Using a Patient-Centric Approach to Evaluate the Burden of Hemophilia B in the United States

Introduction: Persons withhemophilia B (PwHB) require life-long clinical care to prevent and manage bleeding due to a deficiency in coagulation Factor IX (FIX). Observational real-world data (RWD) can provide information regarding the burden of illness experienced by PwHB; however, administrative data sources (eg, insurance claims) used to collect RWD may lack essential clinical information such as disease severity and/or bleeding events. Using a novel patient-centric RWD platform that incorporates multiyear, cross-institutional patient medical records to capture key variables, we assessed the clinical burden among US adults and children with hemophilia B.

Methods: We performed a retrospective cohort study using longitudinal medical record data from the PicnicHealth personal health record platform. PwHB (or caregivers) were identified through social media outreach and patient advocacy groups starting in June 2020 and were required to sign a Health Insurance Portability and Accountability Act authorization for PicnicHealth to retrieve their medical records and share their de-identified data for research. Records were collected from any US provider across all health care facilities who cared for the patient. The study protocol and consent forms received institutional research board approval. Historical data elements were captured from structured and narrative texts using natural language processing and supervised machine learning. Conditions, measurements, drugs, and procedures were mapped to standard medical ontologies. All machine-identified data elements were reviewed by a team of trained abstractors, and quality control was assessed via inter-abstractor agreement. Overall data validity also underwent physician and biostatistician assessments.

The study population included pediatric and adult male PwHB with ≥1 hemophilia B-related medical encounter or FIX treatment documented between 4/1/2015 and 9/30/2020 (first encounter date = index date). PwHB who received any bypassing agent, had a positive inhibitor diagnosis, were enrolled in a clinical trial, or did not have hemophilia severity recorded were excluded. Demographic characteristics, severity, treatment regimen, annualized bleeding rate (ABR), bleeding episodes, and target joints were defined from structured data. Descriptive statistics were reported for ABR, bleeding episodes, and target joints post-index date and were stratified by disease severity and age.

Results: A total of 93 male PwHB were identified within the PicnicHealth data set. There were 75 patients that met the inclusion criteria (median age [range], 21 [0-69] years) with known disease severity levels of mild (n=14), moderate (n=17), and severe (n=44). Most of the patients were White (64%) and aged ≥12 years (75%). Of the 75 patients, 62 received either prophylaxis (55%, n=41) or on-demand only (28%, n=21) FIX treatment. Among PwHB ≥12 years of age for whom sufficient data on bleeding were available (n=35), the median (first quartile [Q1], third quartile [Q3]) ABR during follow-up was 1.5 (0, 4.5) and 3.5 (0, 5.9) for those with mild/moderate and severe hemophilia B, respectively. In PwHB ˂12 years of age (n=13), the corresponding median (Q1, Q3) ABR was 1.3 (0, 2.0) and 0 (0, 5.0). Bleeding incident rates (per 100 person-years) by total bleeding episodes and total target joints (Tables 1 and 2) increased with worsening hemophilia B severity level.

Conclusions: Despite improvements in clinical care, these real-world observational data demonstrate an ongoing burden of bleeding episodes and target joint involvement among pediatric and adult PwHB, with the highest burden occurring in adults with severe hemophilia B.

Patel:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company. Chen:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company. Burton:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company. Alvir:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company. Jeng:Pfizer Inc.: Current Employment. Stachel:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company. Xue:PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Cibelli:PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Fogarty:Pfizer Inc.: Current Employment, Current equity holder in publicly-traded company.