HYDROXYUREA adherence declined significantly over time among patients with sickle cell disease, according to a large longitudinal cohort study examining medication use patterns between 2017–2022. While overall hydroxyurea use remained relatively stable across yearly follow up surveys, adherence worsened steadily and was negatively associated with executive functioning difficulties.
Researchers analysed data from the Sickle Cell Disease Implementation Consortium, a multicentre observational cohort study conducted across eight centres in the United States. The study included patients with sickle cell disease aged 15–45 years who completed self-reported surveys at baseline and up to three annual follow up assessments. Of 2,514 eligible participants, 2,207 completed the baseline survey, with decreasing participation across subsequent follow up periods.
Hydroxyurea Adherence Declined Across Follow Up
At baseline, 49.3% of participants reported current hydroxyurea use. This proportion remained broadly unchanged throughout the study period, with reported use ranging from 47.5–49.3% across all surveys. However, important differences emerged according to genotype and age.
Among patients with HbSS/SB0-thalassemia, hydroxyurea use declined over time, whereas use increased slightly among participants with other genotypes. The trajectory difference between genotype groups reached statistical significance: (odds ratio: 0.76; 95% CI: 0.63–0.91; p=0.004).
Although overall use remained stable, hydroxyurea adherence steadily deteriorated. On average, adherence declined by 0.19 days per week per year: (95% CI: −0.24 to −0.14 days/week/year; p<0.001). Investigators also observed that adherence was lowest among older participants, suggesting reduced treatment sustainment after adolescence.
Executive Function Associated with Poorer Adherence
The analysis identified executive functioning difficulties as a key factor associated with worsening hydroxyurea adherence over time. Participants reporting greater executive difficulties demonstrated significantly poorer adherence trajectories: (−0.17 days/week/year; 95% CI: −0.26 to −0.08 days/week/year; p<0.001).
The authors noted that these findings raise concerns regarding long term disease management among patients with sickle cell disease, particularly those with HbSS/SB0-thalassemia. They suggested that interventions targeting self-monitoring and behavioural activation may help improve sustained hydroxyurea adherence.
Implications for Long Term Disease Management
Despite established therapeutic benefits and treatment recommendations, hydroxyurea remains underused among patients with sickle cell disease. The present findings suggest that maintaining long term adherence may represent a greater challenge than initiating therapy.
The investigators concluded that future interventions should focus on sustaining hydroxyurea adherence beyond adolescence and addressing cognitive barriers that may interfere with consistent medication use.
Reference
Heitzer AM et al. Sustainment of hydroxyurea adherence in patients with sickle cell disease. JAMA Netw Open. 2026;9;(5):e2611257.
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