Background: Hydroxyurea, an antineoplastic agent, was approved in 1998 to reduce the frequency of sickle cell crises in adult patients with sickle cell disease (SCD). More recently in 2017, hydroxyurea was also approved for pediatric patients, 2 years of age and older with sickle cell anemia and recurrent moderate to severe painful crises. Prior to this, hydroxyurea had been used in the United States (US) in pediatric patients with SCD without a labeled indication. This study investigated hydroxyurea utilization patterns among pediatric and adult patients with SCD in the US prior to the pediatric approval using administrative claims data in the Sentinel database sponsored by the US Food and Drug Administration.

Methods: Data from 17 health plans contributing to the Sentinel Distributed Database were queried from January 1, 2000 through September 30, 2015. Eligible patients had a claim with a diagnosis of SCD in any care setting at any time during the query period. SCD was identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Patients were required to be enrolled in plans with both medical and drug coverage on the date of their SCD diagnosis. Patients who were dispensed hydroxyurea after diagnosis of SCD were identified as hydroxyurea users. Patients included in the sub-analysis evaluating hydroxyurea cumulative duration of therapy were required to be continuously enrolled with medical and drug coverage for at least 90 days prior to the initial hydroxyurea dispensing date, during which, gaps in coverage of up to 45 days were allowed. For this sub-analysis, follow-up began on the day of the first valid hydroxyurea dispensing and continued until the first occurrence of any of the following: 1) disenrollment; 2) death; 3) the end date of the data provided by each Data Partner; 4) the end of the last hydroxyurea exposure episode; or 5) the end of the query period. Cumulative duration of hydroxyurea therapy was calculated by summing days' supplies from outpatient pharmacy hydroxyurea dispensings for each patient. Results were stratified by age group (≤1, 2-5, 6-11, 12-17, 18-49, and 50+ years) and race.

Results: A total of 95,606 patients with SCD were identified during the query period. Roughly half of patients (46.8%) were adults 18-49 years of age. Thirty-two percent (n= 30,900) were ≥50 years of age and 20.9% (n= 19,950) were ≤17 years of age. The study population included 40.3% African-American and 15.9% White patients. Race was unknown for 42.6% of the study population. Among pediatric SCD patients ≤1, 2-5, 6-11 and 12-17 years of age, hydroxyurea was dispensed to 4.1%, 7.7%, 16.5% and 16.0% of patients respectively. Among adults 18-49 years and ≥50 years, 18.4% and 4.7% respectively were dispensed hydroxyurea. The majority of pediatric hydroxyurea users were dispensed hydroxyurea for ≥ 325 days cumulatively. The median [inter quartile range] number of days of cumulative hydroxyurea exposure among patients ≤1, 2-5, 6-11, 12-17, 18-49 and 50+ years were 422 [139, 789], 420 [157, 836], 462 [156, 1145], 328 [120, 877], 204 [65, 505] and 253 [88, 599] days respectively.

Conclusions: Although hydroxyurea was not approved for pediatric use in the US until 2017, for the period January 1, 2000 through September 30, 2015, the proportion of pediatric SCD patients 6-11 years and 12-17 years and adult SCD patients 18-49 years of age who were dispensed hydroxyurea were similar in the FDA Sentinel database. Among patients dispensed hydroxyurea, the durations of cumulative exposure were generally higher among pediatric compared to adult patients with SCD. The higher cumulative hydroxyurea exposure duration among pediatric SCD patients may reflect greater tolerability and adherence to hydroxyurea treatment in this population among other reasons. While this analysis evaluated utilization patterns prior to hydroxyurea approval for pediatric SCD patients, further research to evaluate any changes in hydroxyurea use patterns after the pediatric labeling would be useful.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.