Hydroxyurea Use in Sickle Cell Disease: Characteristics Associated With Utilization Following the Revised 2014 NHLBI Guidelines

Background: Sickle cell disease (SCD) is a common blood disorder with potentially debilitating complications including vasoocclusive crises (VOC), acute chest syndrome (ACS), infection and stroke. Hydroxyurea (HU) has been shown to reduce the frequency of these complications and lead to improved survival. The 2002 National Heart, Lung and Blood Institute (NHLBI) guidelines initially recommended HU therapy for individuals with indications of severe SCD. Multiple subsequent large pediatric studies revealed HU was also well tolerated and effective in children. This resulted in the revised 2014 NHLBI guidelines, which recommend HU initiation in all children greater than 9 months old regardless of disease severity. Despite these guidelines and clear evidence demonstrating improved clinical outcomes with HU therapy, initiation and adherence to this medication remains below 50%. This study aims to evaluate HU use and associated characteristics following the revised NHLBI guidelines.

Methods: Retrospective review of the CDC Sickle Cell Data Collection (SCDC) program database in California and Georgia was performed. Hydroxyurea claims, number of complications (ACS, VOC), hospitalizations, emergency department visits and prescribing providers were reviewed across all age groups in two study periods, 2011-2013 and 2014-2016. Data analysis was performed using descriptive analysis, χ2 and Fisher’s exact test.

Results: Following the revised NHLBI guidelines in 2014, there was a statistically significant increase in HU use among the pediatric population in both California (7.9% increase in <10 yo group) and Georgia (4.1% increase in <10 yo group, 6.5% increase in 10-19 yo group). Although not statistically significant, a 4.8% increase in HU use was also observed in the 10-19 yo group in California. Higher HU utilization was seen in those with more complications, specifically in 1 or more ACS event within the study period in California (p = 0.039). Additionally in both study periods, there was a higher ratio of hematologists to non-hematologists prescribing HU in Georgia compared to California.

Conclusions: Although Hydroxyurea use has increased in the pediatric population following the revised NHLBI guidelines in 2014, overall consistent HU use remains low across all age groups, ranging from 2% to 51%. Barriers to HU access must be identified in order to increase HU use and adherence, allowing for reduced complications and improved quality of life in those with SCD.

Resident Statement of Involvement: I was involved in the process of data collection and assisted with data analysis.