Hydroxyurea Adherence and Associated Outcomes in Medicaid Enrollees with Sickle Cell Disease.

Laboratory and clinical benefits of hydroxyurea (HU) for patients with sickle cell disease (SCD) are well-established in the literature, with data drawn primarily from a few randomized trials and several single site observational studies. However, there is a paucity of data on the use of HU in real-world settings among SCD populations. Further, little research exists on the extent and implications of HU non-adherence among SCD patients. This study sought to assess the extent to which children and adults diagnosed with SCD (HbSS and HbSC) are adherent with prescribed HU therapy and potential associations between HU adherence and clinical and economic outcomes.

Retrospective claims of enrollees in the North Carolina Medicaid program (6/1999-8/2008) were analyzed. Inclusion criteria were ≥1 claim with a diagnosis for SCD (i.e., ICD-9-CM 282.6, 282.6x), continuous health plan enrollment for ≥12 months prior to and following HU initiation, and ≥2 HU prescriptions in the 12 months following HU initiation. Adherence was measured using the medication possession ratio (MPR), defined as the sum of days supplied with HU during the 12 months following HU initiation, divided by the number of days in the follow-up period (365), less the number of days hospitalized. Consistent with other studies of adherence, we considered MPR≥0.8 to be adherent. Multivariate regression analyses were used to estimate the association between HU adherence and economic and clinical outcomes (e.g., costs, likelihood of event) in the first year of therapy. In addition to the adherence indicator, covariates included age, gender, race, Charlson Comorbidity Index (CCI) score, and the number of SCD-related office visits in the year prior to HU initiation.

312 subjects (51% male, mean age [SD] 21 [12.2] years) met all inclusion criteria; 51% were '18 years old. The mean MPR was 0.60 (median=0.55), and only 35% of subjects were deemed adherent. Age, race and gender were similar across the adherent and nonadherent groups, while the nonadherent had a slightly higher (though low overall) CCI (0.68 vs. 0.35, p=0.0166) and more SCD-related office visits prior to HU initiation (18.0 vs. 10.6, p=0.0303). Multivariate regression models revealed that in the 12-months following HU initiation, treatment adherence was associated with a significant reduction in both all-cause and SCD-related inpatient (-$4,922, p=0.0010; -$4,383, p<0.0001, respectively) and ER costs (-$564, p=0.0010; -$420, p=0.0010, respectively), as well as SCD-related total costs (-$5,243, p=0.0010). Adherence was associated with an increase in SCD-related pharmacy costs (+$192, p<0.0001) and all-cause office visit costs (+$1,879, p=0.0370). Adherence was also associated with a reduced risk of SCD-related inpatient stay (hazard ratio [HR]=0.65, p=0.0343), ER visit, both all cause and SCD-related (HR=0.72, p=0.0447; HR=0.58, p=0.0080, respectively), and vaso-occlusive event (HR=0.66, p=0.0130). As a sensitivity analysis, we lowered the adherence threshold to ≥0.6; 48% would then be considered adherent. Significant economic benefits (i.e., all-cause and SCD-related inpatient and ER costs; SCD-related total costs) of adherence at the '0.8 threshold were no longer statistically significant using the ≥0.6 definition, but adherence at the lower threshold was still associated with a significant reduced risk of SCD-related ER visits and vaso-occlusive events.

Adherence to HU in patients with SCD may be suboptimal. Adherence to HU is associated with improved outcomes, both clinical and economic.

Off Label Use: Hydroxyurea is approved for adults with sickle cell disease. We will be discussing its use in pediatric and adult patients..