Importance: Despite established treatment guidelines and strong therapeutic benefit, hydroxyurea remains underused among patients with sickle cell disease. Objective: To assess the change in self-reported hydroxyurea use (ie, taking the medication at all) and adherence (ie, the number of days taken per week) over time and to examine factors associated with the trajectory of hydroxyurea use and adherence. Design, Setting, and Participants: Data were collected through the Sickle Cell Disease Implementation Consortium, a longitudinal, multicenter, observational cohort study that recruited patients from 8 centers across the US. Data collection occurred from 2017 to 2022, and analyses were performed from January to October 2025. Data were collected via self-report survey at baseline and 3 follow-up surveys distributed yearly. Patients with sickle cell disease of all genotypes between the ages of 15 and 45 years were included. Exposure: Sickle cell disease. Main Outcomes and Measures: Hydroxyurea use was analyzed as a binary variable according to whether the participant was currently taking hydroxyurea. Among those taking hydroxyurea, adherence was analyzed as a continuous variable according to the number of days hydroxyurea was taken within the past week. Continuous variables were z scored to ensure model convergence, and odds ratios (ORs) are reported. Results: Of 2514 eligible participants, surveys were completed by 2207 participants at baseline, 1802 at follow-up 1, 1281 at follow-up 2, and 783 at follow-up 3. Of 2207 participants at baseline, 1265 (57.3%) were female, with a mean (SD) age of 28.06 (7.86) years. Overall rates of hydroxyurea use remained stable throughout the study (1089 of 2207 patients 49.3% at baseline, 887 of 1802 patients 48.7% at first follow-up, 609 of 1281 patients 47.5% at second follow-up, and 378 of 783 patients 48.3% at third follow-up). However, patients with HbSS/SB0-thalassemia showed declining use (790 of 1550 patients 50.9% at baseline, 627 of 1276 patients 49.1% at first follow-up, 429 of 905 patients 47.4% at second follow-up, and 282 of 586 patients 48.1% at third follow-up), whereas patients with other genotypes showed increasing use (299 of 657 patients 45.5% at baseline, 250 of 526 patients 47.5% at first follow-up, 168 of 352 patients 47.7% at second follow-up, and 90 of 186 patients 48.4% at third follow-up) across time points (OR, 0.76; 95% CI, 0.63 to 0.91; P = .004). Hydroxyurea adherence declined over time (-0.19 days/week/year; 95% CI, -0.24 to -0.14 days/week/year; P < .001). Executive difficulties were associated with worse adherence across time points (-0.17 days/week/year; 95% CI, -0.26 to -0.08 days/week/year; P < .001). Conclusions and Relevance: In this cohort study of patients with sickle cell disease, declining use of hydroxyurea among patients with HbSS/SB0-thalassemia genotypes raises important concerns about ongoing disease management. Adherence to hydroxyurea is negatively associated with cognitive factors that may be addressed through interventions targeting self-monitoring and/or behavioral activation.
Heitzer et al. (Wed,) studied this question.