Factors associated with longitudinal hydroxyurea adherence trajectories among individuals with sickle cell disease in...

Hydroxyurea, first-line therapy in sickle cell disease (SCD), has suboptimal adherence ranging from 10%-36%. Thus, examining longitudinal adherence trajectories may help identify critical timepoints and individual subgroups for targeted interventions.

To identify distinct longitudinal hydroxyurea adherence trajectories among individuals with SCD enrolled in Texas Medicaid and to examine sociodemographic and clinical factors associated with trajectory group membership.

Retrospective, longitudinal cohort study.

A retrospective analysis of Texas Medicaid data (01/01/2016-08/31/2023) included individuals with ≥3 medical claims for SCD, ≥1 prescription claim for hydroxyurea without a claim in the pre-index period, aged 2-63 years on the index date (first hydroxyurea claim), and continuously enrolled in Texas Medicaid for 6 months pre- and 12 months post-index. Proportion of days covered (PDC) was used to estimate adherence. Group-based trajectory modeling (GBTM) was used to identify hydroxyurea adherence trajectories. Multinomial logistic regression was used to examine factors associated with hydroxyurea adherence trajectory group membership.

Of included individuals (N=1,246; mean age=18.1±12.7, 50.8% female), GBTM revealed five membership groups: consistent adherence (16.1%; mean PDC=89.2±8.5%), fluctuating adherence (28.7%; mean PDC=52.6±12.8), sharp decline and fluctuating adherence (16.5%; mean PDC=26.2±8.8), rapidly decreasing adherence (22.2%; mean PDC=25.6±10.3), and early and consistent nonadherence (16.5%; mean PDC=8.4±1.3). Potential intervention timepoints were identified at months 2, 3, and 5, when adherence declined markedly. Age groups 16-21, 22-34, and ≥35 years (reference: 2-15 years), and an increasing number of vaso-occlusive crises (VOC) in the pre-index period were significantly associated with higher odds of being in the less-adherent trajectory groups compared to the consistent adherence trajectory group: adjusted odds ratio (aORs) range: age groups=2.2-8.7; VOC=1.2-1.4.

Unique adherence trajectory patterns with critical timepoints for intervention were observed. Individualized and timely interventions should be tailored to adults, especially those who are transitioning to adult care (22-34 years), and those experiencing frequent VOC.