Hydroxyurea Use in Children with Sickle Cell Disease: Do Severely Affected Patients Use It and Does It Impact Hospitalization Outcomes?

Field: Medicine (Health Sciences)

Abstract Background The2014 National Heart, Lung, and Blood Institute Expert Panel Report recommends that hydroxyurea (HU) be offered to all children with Hemoglobin SS and Sβ0 sickle cell disease (SCD) and that it be considered for children with Hemoglobin SC or Sβ+ who have clinically severe SCD. Describing current HU use among hospitalized children with SCD could identify whether HU is being prescribed to children who may benefit from it and whether HU improves hospitalization outcomes. Objectives The primary aims of this study were to determine the current rate of HU use in hospitalized children and to determine if HU was differentially used in children with clinically severe SCD. Additionally, we examined if hospitalized HU users had improved hospitalization outcomes as measured by fewer deaths, shorter lengths of stay (LOS), fewer intensive care unit (ICU) admissions, and fewer erythrocyte transfusions compared to HU non-users. Methods We performed a retrospective analysis of the Pediatric Health Information System (PHIS) inpatient data, a dataset developed by the Children's Hospital Association. PHIS participating hospitals supply International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, de-identified demographic data, procedure codes, and charge codes for all of their hospitalization discharges. We included children ages 2-18 with SCD discharged between January 1, 2011-September 30, 2014 from the 42 hospitals that provided complete data to PHIS during the study period. Only patients' most recent hospitalization during the study period was analyzed to reflect the current rate of HU use. The following patient data within PHIS were obtained for all eligible discharges: age, gender, HU use, discharge status (dead, alive), ICU admission, asthma diagnosis, total number of ICD-9-CM diagnoses, LOS (days), erythrocyte transfusion, and insurance provider (private, public, unknown). Since the ICD-9-CM codes for patients' SCD genotype are not discreet, we did not use SCD genotype in our analyses. We defined patients as having clinically severe SCD if they had a history of a recent ICU admission (after 2009) or a history of ≥3 hospital admissions in the year preceding their most recent admission. This severity definition was selected because it is used in clinical practice or in clinical trials to identify children with severe SCD and because it could be captured within PHIS. Chi-squared and t-tests were used to compare the two groups, and since this was an observational study, propensity score weighting was used to balance differences in the baseline characteristics between HU users and non-users. Results We identified 2,665 unique children with SCD. Approximately 80% had an inpatient code indicating HU use. The mean age of HU users was 11.1 years (SD ± 4.8), which was younger (p=0.013) than non-users (11.7 years SD ± 4.8). Two HU users and four non-users died during their hospitalization. Significantly more (p<0.001) non-users (30.1%) had a prior ICU admission compared to HU users (18.7%). More non-users (33.9%) also had a history of three or more admissions compared to HU users (21.5%) (p<0.001). HU use did not significantly differ (p=0.08) by public (81.2%), private (83%), or unknown (70.2%) insurance provider. After applying propensity score weighting to balance these differences, HU users' and non-users' LOS, prevalence of ICU admissions, and prevalence of erythrocyte transfusions during their most recent hospitalizations did not significantly differ. Discussion Our study confirms that HU use is high among hospitalized children with SCD. However, we find that HU is not utilized by many children with clinically severe SCD, despite few other available therapies. Prior clinical trials show that HU use reduces hospitalizations, but our findings do not support that HU improves inpatient outcomes in those who are hospitalized. Our results support consideration of HU in children with SCD to prevent their hospitalization, rather than as a treatment to improve their hospitalization outcomes. Additional treatment options are needed for hospitalized children to reduce their LOS, ICU admissions, and erythrocyte transfusions. Disclosures Off Label Use: Hydroxyurea is a FDA approved medication for adults with sickle cell disease but it is not currently approved for children. Hydroxyurea induces fetal hemoglobin production and results in reduced complications in patients with sickle cell disease. There are multiple clinical trials showing that it is safe and effective for children with sickle cell disease..