Impact of Prophylaxis Usage on Bleeding Rates Among Persons with Hemophilia A: Evidence from Longitudinal Analyses in the USA
Authors: Nichol Michael B. , Curtis Randall , Ding Yuchen , Aliyev Elmar R. , Koerper Marion A. , Lou Mimi , Ullman Megan M. , Tran Duc Quang , Baker Judith , Riske Brenda , Wu Joanne 
Published: October 2019

Abstract
BACKGROUND
There are limited longitudinal studies following up persons with hemophilia (PWH) in adherence to clotting factor treatment and health outcomes. The Hemophilia Utilization Group Studies part Va (HUGS Va) was a two-year observational study of persons with hemophilia A conducted from 2005-2007. Participants from HUGS Va were enrolled to the long-term follow-up study (HUGS LTS) in 2014.
OBJECTIVES
To compare participants' characteristics between baseline of HUGS Va and follow-up in LTS; and investigate the impacts of changes of participants' characteristics on annualized bleeding rates.
METHODS
We collected data on sociodemographic and clinical characteristics. Self-reported bleedings were obtained from periodic surveys for 2-years in HUGS Va, and a survey that asked bleedings in the past 6-month in HUGS LTS. Clotting factor dispensing records were collected prospectively for two years in HUGS Va, and retrospectively for six months prior to HUGS LTS enrollment. Annualized bleeding rates and factor dispensing (unit/kg body weight) were calculated. Adherence to factor treatment was determined by the ratio of dispensed clotting factor to clinical recommended factor usage. We classified age at baseline of HUGS Va into three groups: children (aged 2-11 years), adolescents (aged 12-20 years), and adults (aged ≥21 years). The characteristics of participants were compared among the three age groups using Chi-square tests for categorical variables and ANOVA for continuous variables for each study. Annualized factor dispensed and bleeding rates were compared between HUGS Va and HUGS LTS using paired T-tests.
RESULTS
A total of 74 persons participated in both HUGS Va and LTS with completed data to calculate annualized factor dispensed and bleeding rates were included to the analyses. The mean age was 17.8±11.4 years in HUGS Va, and 26.2±11.5 years in LTS, respectively. The sample had 43% of children, 22% adolescents, and 35% adults at baseline. All adolescents at baseline transitioned to young adults in LTS. Approximately 80% of participants were severe hemophilia. Adults (73%) were less likely to have an entire year of health insurance as compared to children (100%) or adolescents (93.8%, P<0.01) in HUGS Va. Health insurance status was not significantly different among age groups in LTS. In HUGS Va, children had the highest rate of prophylactic treatment (74%), adherence to factor treatment (62%), highest mean annualized factor dispensed (4724±4090 u/kg), lowest rate of self-reported moderate or severe joint pain (31%), and lowest mean annualized bleeding rate (4.2±4.7); while adults had the lowest rate of prophylactic treatment (31%), adherence (28%), lowest mean annualized factor dispensed (2084±1870 u/kg), highest rate of self-reported moderate or severe joint pain (73%), and highest mean annualized bleeding rate (11.9±9.3), all P<0.05 among age group comparisons for these variables. There were 18 (26%) people (22% children, 17% adolescents, and 61% adults) switching from episodic treatment to prophylactic treatment from HUGS Va to LTS; others remained on the same treatment regimens. Adolescents and adults increased in prophylactic treatment (63% to 80% for adolescents, 31% to 69% for adults, respectively), adherence (36% to 75%, 28% to 61%), and mean annualized factor dispensed (3206±2581 to 4931±2945 u/kg, 2084±1870 to 4612±2577 u/kg) from HUGS Va to LTS. Mean annualized bleeding rates were not statistically significant different between HUGS Va (7.3±8.4) and LTS (10.6±22.0, P>0.05). The bleeding rates were not significantly different among age groups in LTS (P=0.06).
CONCLUSIONS
Although current literature indicated that PWH in transition from childhood to adulthood maybe at high risk of adverse health outcomes due to poor management of their condition with diminishing influence from parents, adolescents showed a significant increase in prophylactic treatment, adherence to factor treatment, and annualized factor dispensed, which may be associated with unchanged annualized bleed rates after they transitioned to adulthood in this study. Adults had a larger increase in dispensed factors than adolescents. Prophylaxis and adherence to clotting factor treatment were associated with a lower bleeding rate. Our current analyses reinforce the importance of prophylaxis and adherence to factor treatment for decreasing bleedings in persons with hemophilia A.

Disclosures
Nichol: Bayer: Research Funding; CSL Behring: Research Funding; Bioverativ: Research Funding; Shire/Baxter: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding. Curtis:Gilead: Honoraria; Pfizer: Research Funding; Novo Nordisk: Honoraria, Research Funding; Shire/Baxter: Research Funding; Bioverativ: Research Funding; National Hemophilia Foundation: Honoraria; CSL Behring: Research Funding; Bayer: Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding. Ding:Novo Nordisk: Employment; Bioverativ: Research Funding. Aliyev:Genentech: Research Funding. Lou:Bioverativ: Research Funding; Novo Nordisk: Research Funding; Genentech: Research Funding; Bayer: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Shire/Baxter: Research Funding. Ullman:Genentech: Research Funding. Tran:Bioverativ: Honoraria; Novo Nordisk: Honoraria; Bayer: Honoraria; Genentech: Research Funding. Baker:Genentech: Research Funding. Riske:Genentech: Research Funding. Wu:Pfizer: Research Funding; Genentech: Research Funding; Bioverativ: Research Funding; CSL Behring: Research Funding; Bayer: Research Funding; Shire/Baxter: Research Funding; Novo Nordisk: Research Funding.