Ten‐year longitudinal analysis of hydroxyurea implementation in a pediatric sickle cell program

Abstract

Hydroxyurea (HU) has proven benefit in sickle cell anemia (SCA), but HU is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia prescribes HU regardless of symptoms to all SCA patients age ≥ 9 months and prospectively tracks outcomes. HU is dosed to maximum tolerated dosing (MTD), targeting 30% Hgb F. Longitudinal data from 2009 to 2019 encompassing 1222 HU‐eligible and 950 HU‐exposure patient‐years were analyzed in 2‐year intervals for hemoglobin (Hgb), fetal hemoglobin (Hgb F), hospitalizations, transfusions, and treat‐and‐release ED visits. Comparing HU‐eligible patients in the interval prior to HU implementation (2009–2011) to the last interval analyzed after HU implementation (2017–2019), HU usage increased from 33% to 93%, average Hgb increased from 8.3 ± 0.98 to 9.8 ± 1.3 g/dl (p < .0001), average Hgb F rose from 13 ± 8.7% to 26 ± 9.9% (p < .0001), hospitalizations decreased from 0.71 (95% CI 0.54–0.91) to 0.2 (95% CI 0.13–0.28) admissions/person‐year, sporadic transfusions decreased from 0.4 (95% CI 0.27–0.55) to 0.05 (95% CI 0.02–0.12) transfusions/person‐year. Treat‐and‐release ED visit rates remained unchanged, varying between 0.49 (95% CI 0.36–0.64) and 0.64 (95% CI 0.48–0.83) visits/person‐year. By the last interval, 72% of patients had Hgb ≥ 9 g/dl, 42% had Hgb F ≥ 30%, 79% experienced no hospitalizations, and 94% received no transfusions. Uniform HU prescription for SCA patients with close monitoring to achieve high Hgb F resulted in significant improvements in laboratory and clinical outcomes within 2 years, which continued to improve over the next 6 years. Rigorous HU implementation in a pediatric sickle cell population is feasible, effective, and sustainable.

High hydroxyurea usage in sickle cell anemia regardless of patient demographics

“…Reported here is additional analysis of results from our previously published uniform HU implementation program, 1…”

“…The Northern Virginia study reported on all patients in the program with SCA regardless of insurance coverage, thus raising the question of whether the high HU usage rate achieved in this program was influenced by a high proportion of non‐Medicaid patients or other unusual demographic features. Therefore, we analyzed our previously reported HU usage data 1 by insurance, ethnicity, and age.…”

“…The Pediatric Sickle Cell Program of Northern Virginia recently published a 10‐year analysis of uniform hydroxyurea (HU) implementation starting in infancy for all patients with sickle cell disease of severe genotype, referred to as sickle cell anemia (SCA) 1 . The HU implementation program targeted high fetal hemoglobin (Hgb F) with close adherence monitoring.…”

An integrated therapeutic approach to sickle cell disease management beyond infancy

“…In a community‐based study where HU was given to infants >9 months old who were followed for at least 6 years, HbF rose from 13 ± 8.7% to 26 ± 9.9% while hospitalizations decreased from 0.7 to 0.2 admissions per person‐year, and the incidence of ACS decreased from 14.6 to 4.2 per 100 patients‐years 24 . By the last 2‐year interval of follow‐up, 72% of patients had total hemoglobin >9 g/dL, 42% had HbF >30%, 79% experienced no hospitalizations, and 94% received no transfusions 25 . Despite its benefits HU is not a “cure.” Dosing in adults is often a challenge because of poor adherence, a dearth of knowledgeable adult providers, myelotoxicity, and diminished bone marrow reserve 16,26–29 .…”

“…24 By the last 2-year interval of follow-up, 72% of patients had total hemoglobin >9 g/dL, 42% had HbF >30%, 79% experienced no hospitalizations, and 94% received no transfusions. 25 Despite its benefits HU is not a "cure." Dosing in adults is often a challenge because of poor adherence, a dearth of knowledgeable adult providers, myelotoxicity, and diminished bone marrow reserve.…”