Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia

Abstract

Background Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real‐world implementation in high‐income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. Procedure We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients’ electronic medical record. Participants with a hydroxyurea exposure >20 mg/kg/day and ≤20 mg/kg/day were included in the higher and lower exposure groups, respectively. Results Forty‐five participants were included in the analysis (56% male; median age 12 years [range 2–19]; 98% Black). Higher exposed participants (n = 23) were prescribed a higher dose (27.2 vs. 24.4 mg/kg/day, p = .002) and had better adherence (0.92 vs. 0.71, p ≤ .001) compared to lower exposed participants (n = 22). Higher exposure was associated with higher fetal hemoglobin (p = .04) and mean corpuscular volume (p = .02). Conclusions Higher hydroxyurea exposure is associated with improved hematologic parameters in the high‐income setting and is affected by both prescribed dose and adherence. Future studies are needed to optimize both adherence and hydroxyurea prescribing and confirm that increasing exposure improves clinical outcomes in this setting.

Impact of hydroxyurea on clinical and biological parameters of sickle cell anemia in children in Abidjan

“… 10 This induction of Hb F leads to a decrease in Hb S. In our series, the mean Hb S level decreased from 87.5% to 75.7% after 6 months of treatment, a result beneficial for the patients. Creary et al 9 also observed this decrease in Hb S with hydroxyurea.…”

“…This induction of Hb F production has been observed by other authors. 9 This increase in Hb F reduces complications related to this disease. Hydroxyurea induces the production of Hb F and increases the volume of red blood cells, thus reducing the risk of Hb S polymerization.…”

Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease

“…Hydroxyurea is the primary disease modifying therapy for SCD, with more than 40 years of evidence demonstrating remarkable effectiveness to reduce acute complications, mitigate many long-term costly SCD comorbidities, and improve survival [9][10][11][12][13][14]. Despite calls to increase hydroxyurea use among youth with SCD in the last decade, [15] their high rate of emergency department visits and hospitalizations have not significantly changed, [16] Non-adherence is a key reason for hydroxyurea's limited impact, [17][18][19][20][21][22] as only 18-66% of youth achieve the level of hydroxyurea adherence seen in the pediatric trial that established its efficacy [18][19][20]23]. Studies suggest that patient-level hydroxyurea adherence barriers include forgetting, competing priorities, and having to deal with SCD daily, while understanding hydroxyurea's benefits, feeling better, and receiving support from others facilitate adherence [21,24,25].…”

Barriers to medication adherence in sickle cell disease: A comprehensive theory‐based evaluation using the COM‐B model

“…[8][9][10][11] Given the phenotypic variations in SCD, the decision-making process for disease-modifying therapies in SCD is complex and can affect treatment adherence. 12 Hydroxyurea (HU) is approved by the US Food and Drug Administration (FDA) for SCD given the strong evidence for safety and efficacy, [13][14][15][16] with the National Heart, Lung, and Blood Institute recommending it starting at 9 months of age. 17 Treatment with HU reduces hospitalization rates, 18,19 decreases number of VOCs, 15 and improves HRQoL for people with SCD.…”

“…Hydroxyurea (HU) is approved by the US Food and Drug Administration (FDA) for SCD given the strong evidence for safety and efficacy, 13–16 with the National Heart, Lung, and Blood Institute recommending it starting at 9 months of age 17 . Treatment with HU reduces hospitalization rates, 18,19 decreases number of VOCs, 15 and improves HRQoL for people with SCD 20 .…”