George Paul, Kalmus Grace, Lane Peter A, Lam Wilbur, Lipscomb Joseph, Howard David
Division of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA.
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Blood Adv. 2025 Jul 22;9(14):3585-3593. doi: 10.1182/bloodadvances.2024015564.
Hydroxyurea is the primary disease-modifying medication for sickle cell anemia (SCA), but its long-term effects, particularly how these effects change over time, are not well understood. This study aimed to quantify the effects of hydroxyurea on clinical and laboratory outcomes in children with SCA over a prolonged period of use. We conducted a quasi-experimental study using contemporary difference-in-differences and dynamic event study analyses on a longitudinal cohort of 2147 children with SCA (hemoglobin SS or hemoglobin SSβ0, HbSS/HbSβ0) from 2010 to 2021. The primary outcomes included emergency department (ED) visits per year, hospital days per year, and annual average hemoglobin concentration. Hydroxyurea use was associated with fewer ED visits per year (average treatment effect on the treated [ATT], -0.36 visit per year; 95% confidence interval [CI], -0.57 to -0.16) and fewer hospital days per year (ATT, -0.84 d/y; 95% CI, -1.51 to -0.17) with sustained effects over time. On average, the hemoglobin concentration increased with hydroxyurea use (ATT, 0.56 g/dL; 95% CI, 0.39-0.73), but the sustained effect was observed only among the subgroup with laboratory markers of good adherence. This study demonstrates that hydroxyurea has sustained clinical benefits in reducing ED visits and hospital days across years of use in children with SCA. These findings provide perspective for clinicians and families regarding the long-term efficacy of hydroxyurea in pediatric SCA management and underscore the importance of ongoing adherence counseling to optimize clinical benefit. Furthermore, this study design provides a methodological framework for rigorously and causally evaluating other SCA-specific treatments, such as stem cell transplant and gene therapy, in real-world settings.
羟基脲是治疗镰状细胞贫血（SCA）的主要病情改善药物，但其长期影响，尤其是这些影响如何随时间变化，目前尚不清楚。本研究旨在量化羟基脲在长期使用过程中对SCA患儿临床和实验室指标的影响。我们对2010年至2021年期间2147名SCA患儿（血红蛋白SS型或血红蛋白SSβ0型，HbSS/HbSβ0）的纵向队列进行了一项准实验研究，采用当代差分法和动态事件研究分析。主要指标包括每年的急诊科就诊次数、每年的住院天数以及年平均血红蛋白浓度。使用羟基脲与每年较少的急诊科就诊次数（对治疗组的平均治疗效果[ATT]，每年-0.36次就诊；95%置信区间[CI]，-0.57至-0.16）和每年较少的住院天数（ATT，-0.84天/年；95%CI，-1.51至-0.17）相关，且随着时间推移效果持续。平均而言，使用羟基脲后血红蛋白浓度升高（ATT，0.56 g/dL；95%CI，0.39 - 0.73），但仅在依从性良好的实验室指标亚组中观察到持续效果。本研究表明，在SCA患儿多年使用过程中，羟基脲在减少急诊科就诊次数和住院天数方面具有持续的临床益处。这些发现为临床医生和家庭提供了关于羟基脲在儿科SCA管理中的长期疗效的观点，并强调了持续进行依从性咨询以优化临床益处的重要性。此外，本研究设计为在现实环境中严格且因果性地评估其他SCA特异性治疗方法，如干细胞移植和基因治疗，提供了一个方法框架。
