Analysis of Bleeding and Treatment Patterns in Children and Adolescents before and after Von Willebrand Disease Diagnosis Using Data from a US Medical Claims Database
Authors: Roberts Jonathan C. , Malec Lynn M , Halari Imrran , Hale Sarah , Oladapo Abiola , Sidonio Robert 
Published: November 2019

Background: Von Willebrand disease (VWD) is the most common bleeding disorder found in children and adolescents. It has a varied clinical presentation, which likely contributes to challenges and delays in the correct diagnosis and the subsequent management of the disease.
Objective: To characterize diagnosis, bleeding, and treatment patterns in children (2-11 years of age) and adolescents (12-17 years of age) with VWD.
Methods: This retrospective database analysis utilized data from the IQVIA PharMetrics Plus Database of medical insurance claims for patients with VWD (ICD-9 286.4) from January 1, 2006 to June 30, 2015. Patients included had ≥2 medical claims for VWD and continuous enrollment for ≥2 years, to ensure a higher likelihood of definitive VWD diagnosis, before and after their 1st VWD claim. The pre-diagnosis period included 18 months of data before diagnosis. The post-diagnosis period included 7-24 months post-diagnosis data. Data from the first 6-month post-diagnosis period were excluded due to data variability, suggestive of treatment optimization. Descriptive statistics were used to summarize patient demographic and clinical characteristics, including types of bleeding episode (BE), rates, and outcomes; treating physician specialty; and type of VWD treatment, in both the pre- and post-diagnosis periods.
Results: Of 1087 patients identified, 475 were children (43% female) with a mean (SD) age at VWD diagnosis of 6.9 (2.7) years, and 612 were adolescents (74% female) with a mean (SD) age at VWD diagnosis of 14.9 (1.6) years.
The top 3 treating physician specialties seen by children in the pre- and post-diagnosis periods, respectively, were hospitalists (21% and 9%), primary care physicians (16% and 7%), and hematologists (11% and 3%). Adolescents were mostly seen by hospitalists (30% and 15%), primary care physicians (25% and 16%), and obstetrician gynecologists (19% and 15%). Only 11% of children and adolescents saw a hematologist prior to diagnosis, compared with 3% and 5%, respectively, post-diagnosis.
A 17% vs. a 15% decrease in bleed claims in the pre- vs. post-diagnosis period was observed among children (40% vs. 23%) and adolescents (59% vs. 44%), respectively.
The most common type of BE among children in the pre- and post-diagnosis periods was epistaxis (19% and 10%), and the trend was similar for boys and girls. Heavy menstrual bleeding was the most common BE type among adolescents overall in both the pre- and post-diagnosis periods (40% and 30%; in females 54% and 40%). Epistaxis was the second most common BE among adolescents overall in both the pre- and post-diagnosis periods (11% and 7%), and in females (9% and 5%), but the highest among males (17% and 12%). Of note, 3% of children had gastro-intestinal (GI) bleeds pre-diagnosis, reducing to 1% post-diagnosis. In adolescents, 1% had GI bleeds pre-diagnosis, rising to 2% post-diagnosis.
Overall, VWD related treatment claims increased between the pre- and post-diagnosis periods for both children (12% vs. 23%) and adolescents (31% vs. 50%).
The most prescribed treatments for bleed management in children were aminocaproic acid (ACA), desmopressin (DDAVP) and nasal cauterization (pre-diagnosis: 5%, 4% and 4%, respectively; post-diagnosis: 11%, 13% and 3%, respectively). For adolescents, the most prescribed treatments, pre- and post-diagnosis respectively, were oral contraceptives (22% [females 29%, males 0%] and 33% [females 45%, males 0%]), DDAVP (9% [females 8%, males 12%] and 19% [females 20%, males 14%]) and ACA (4% [females 4%, males 5%] and 11% [females 12%, males 7%]). Of note, 3% and 4% of children and 2% and 4% of adolescents received plasma-derived VWF concentrates pre- and post-diagnosis respectively.
Conclusions: This analysis demonstrates a decrease in BE claims following VWD diagnosis and a rise in ACA and DDAVP treatment claims in both children and adolescents, and in oral contraceptive claims among female adolescents. Nevertheless, a considerable proportion of children and adolescents continue to experience BEs 6 months post-diagnosis. This emphasizes the need for treatment optimization and improvement in the care and management of patients in these age groups.

Disclosures
Roberts: Shire, a Takeda company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bioverativ: 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; Octapharma: Membership on an entity's Board of Directors or advisory committees; Spark: Membership on an entity's Board of Directors or advisory committees. Malec:Spark: Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Bayer: Honoraria; Takeda: Honoraria; CSL: Honoraria. Halari:Charles River Associates: Employment. Hale:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Oladapo:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Sidonio:Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire, a Takeda company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; BioMarin: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; uniQure: Membership on an entity's Board of Directors or advisory committees.