(WASHINGTON, April 17, 2024) — Hydroxyurea remains effective long-term in reducing emergency department visits and hospital days for children living with sickle cell disease (SCD), according to new research published in Blood Advances.
"This is one of the first large, real-world, long-term studies to assess the efficacy of hydroxyurea outside of a controlled setting," said study author Paul George, MD, a pediatric hematology/oncology fellow and PhD candidate at Emory University School of Medicine and Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta. "Our results reinforce that hydroxyurea, the most efficacious medicine available for SCD, continues to have really important benefits over time for pediatric patients."
SCD is the most common inherited red blood cell disorder in the United States, affecting an estimated 100,000 people. According to the Centers for Disease Control and Prevention, SCD affects one out of every 365 Black or African American births and one out of every 16,300 Hispanic American births. The disorder is characterized by abnormally shaped blood cells that can become lodged in the veins, blocking blood flow and leading to organ damage, infection, and episodes of severe pain.
Hydroxyurea, an oral, once-daily, and typically life-long medication, reduces the frequency and severity of SCD pain crises, in addition to decreasing the need for blood transfusions, improving anemia, and reducing the risk of acute chest syndrome, when abnormally shaped blood cells block vessels in the lungs. Currently, the National Heart, Lung, and Blood Institute recommends that hydroxyurea be offered as a therapy to every patient with the more severe variant of SCD, HbSS/HbSβ0 starting between nine to twelve months of age.
"Hydroxyurea has been a mainstay in SCD treatment for a long time, but was initially used as a chemotherapy, so there have always been some lingering fears about its safety and efficacy, especially for children," said study author Wilbur Lam, MD, PhD, a professor of pediatrics and biomedical engineering at Emory University and at the Georgia Institute of Technology and a pediatric hematologist at Children's Healthcare of Atlanta. "This study can provide some reassurance to patients and their families that this therapy, one of the most accessible for SCD, continues to be a safe option with a true benefit outside of a controlled setting."
The study's total cohort was made up of 2,147 children under the age of 18. All participants had the HbSS/HbSβ0 variant of SCD, had more than three clinical encounters between 2010 and 2021 at Children's Hospital of Atlanta, and had not received a bone marrow transplant, gene therapy, chronic transfusion therapy, or treatment with disease-modifying medications outside of hydroxyurea. Of the 2,147 participants, 1,240 (58%) had used hydroxyurea; of those, the average time on hydroxyurea was 5.1 years, with 304 children aged eight or older on continuous hydroxyurea therapy.
The researchers found that, generally, children using hydroxyurea visited the emergency department less (0.36 fewer visits per patient-year) and spent fewer days in the hospital (0.84 fewer days per patient-year) across prolonged use when compared to children not on hydroxyurea. These results remained consistent even when the researchers accounted for disease severity and adherence by including only patients who began hydroxyurea at age one – before severe symptoms typically emerge – and limiting the sample to patients with laboratory markers that indicated consistent medication intake.
"Overall, hydroxyurea remained effective over time in these children," said Dr. George. "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." Dr. George added that these results reflect real-world use and point to a continued need for providers to emphasize to patients the importance of taking hydroxyurea every day.
The researchers cautioned that the study does have some data limitations due to its real-world nature, including the reliance on laboratory markers to determine hydroxyurea adherence and lack of data on intermittent transfusions and acute events causing ongoing anemia, such as pain crises. They hope to make up for these gaps in data in future studies and incorporate patient-reported outcomes to better gauge how hydroxyurea impacts children outside of the hospital setting.
