Hydroxyurea Produces Long-Term Clinical Benefits in Pediatrics With Sickle Cell Anemia

Hydroxyurea, the standard of care disease-modifying treatment for sickle cell anemia (SCA), is effective at sustaining clinical benefits, including reductions in emergency department (ED) visits and hospital days, across years of use in children with SCA, according to new findings published by investigators in Blood Advances.^1,2

Sickle cell anemia is characterized by the "sickle" shape of red blood cells in patients. | Image Credit: © nick - stock.adobe.com

Hydroxyurea's Effectiveness in Sickle Cell Anemia

According to guidelines from an expert panel from the National Heart, Lung, and Blood Institute, hydroxyurea should be offered for all pediatrics aged 9 to 12 months and older with SCA, regardless of their disease severity. Experts have determined that hydroxyurea should be considered first-line, standard-of-care treatment for SCA, with earlier administration and broader use of the treatment critical to allowing affected patients to live longer lives. As it stands, there is not a medication with similar efficacy for patients with SCA.^1,3,4

“Hydroxyurea has been a mainstay in SC [disease] treatment for a long time but was initially used as chemotherapy, so there have always been some lingering fears about its safety and efficacy, especially for children,” Wilbur Lam, MD, PhD, professor of pediatrics and biomedical engineering and study author, said in an accompanying news release.²

Because patients with SCA are often treated with hydroxyurea for many years, it is pertinent for research to focus on the long-term effects of treatment and whether hydroxyurea can remain effective over time. Accordingly, the investigators note in their study that, while the long-term benefits of hydroxyurea use compared with no hydroxyurea have been established, there is a lack of published literature on the time-varying effect of hydroxyurea.¹

“This is one of the first large, real-world, long-term studies to assess the efficacy of hydroxyurea outside of a controlled setting,” Paul George, MD, pediatric hematology/oncology fellow and PhD candidate at Emory University School of Medicine and study author, said in the news release. SCA is one of the most common inherited red blood cell disorders in the US, making investigations into whether the effects of treatment wane over time imperative.²

Data Shows Sustained Effects of Hydroxyurea Over Time

Authors of the current study initiated a quasi-experimental, observational study to analyze the effects of hydroxyurea change over time using real-world data on a longitudinal cohort of children with SCA. The cohort was made up of 2147 children under the age of 18 with the HbSS/HbSβ0 variant of SCA who had not received any disease-modifying medications other than hydroxyurea and who had over 3 clinical encounters at Children’s Hospital of Atlanta. Among the cohort, 1240 (58%) of patients had used hydroxyurea; the average time using hydroxyurea was 5.1 years, and there were 304 children aged 8 years or older on continuous therapy.^1,2

According to the authors’ primary models, hydroxyurea use was associated with fewer ED visits per patient year (average treatment effect on the treated [ATT]: -0.36 visits/year; 95% CI: -0.57, -0.16). It was also associated with a reduction in hospital days per patient year, with an ATT of -0.84 visits/year (95% CI, -1.51, -0.17), with an event study analysis indicating a steady effect over time, according to the investigators. Importantly, the results remained consistent even when the investigators only included patients who began hydroxyurea at age 1, before severe symptoms emerged.^1,2

“Overall, hydroxyurea remained effective over time in these children,” George said to conclude. “However, one important takeaway from this study is that improvements in hemoglobin concentration—or reductions in anemia—were seen only in patients whose data indicated they were regularly taking the medication.”²

Pharmacists can be assured that hydroxyurea treatment will remain effective and sustain reductions in hospital visits over multiple years of treatment in pediatric patients. They should continue to prescribe the treatment as a first-line approach to treating patients with SCA.

REFERENCES

1. George PE, Kalmus GG, Lane PA, Lam WA, Lipscomb J, Howard D. Evaluating the long-term benefits of hydroxyurea in pediatric sickle cell anemia. Blood Adv. 2025. doi:10.1182/bloodadvances.2024015564

2. American Society of Hematology. Real-world study finds hydroxyurea effective long-term in children living with sickle cell disease. Published April 17, 2025. Accessed April 24, 2025. https://www.hematology.org/newsroom/press-releases/2025/hydroxyurea-effective-long-term-in-children-living-with-scd#:~:text=(WASHINGTON%2C%20April%2017%2C%202024,research%20published%20in%20Blood%20Advances.

3. Yawn BP, Buchanan GR, Afenyi-Annan A, et al. Management of sickle cell disease: Summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048. doi:10.1001/jama.2014.10517

4. McGann PT, Ware RE. Hydroxyurea therapy for sickle cell anemia. Expert Opin Drug Saf. 2015;14(11):1749-1758. doi:10.1517/14740338.2015.1088827