6124 Adherence to hydroxycarbamide in a high-uptake paediatric sickle cell cohort; insights from various measurement approaches

Objectives Adherence to hydroxycarbamide, the only licensed disease-modifying medication for pediatric sickle cell patients in the UK, has been reported to be suboptimal.¹ However, there is currently no standardized biomarker or objective assessment tool for measuring adherence. In this study, our objective was to measure adherence to hydroxycarbamide in pediatric sickle cell patients using various methodologies and identify factors that may influence adherence based on patient and treatment characteristics. Methods We included all pediatric sickle cell patients who had been on hydroxycarbamide for more than six months. A mixed methodology approach was employed to assess adherence, which included an anonymous online patient questionnaire, laboratory parameters (HbF level, neutrophil count, MCV), and medication possession ratios (MPRs), defined as the number of days covered by prescription in a time period, divided by the total number of days in that time period. Multivariate regression analysis, performed with SPSS, was used to evaluate the impact of different clinical parameters on adherence as measured by HbF, neutrophil count, and MPRs. Results A total of 61 patients (32 female, mean age 9.4±4.4 years) were included, which correlates to an uptake rate of 75% of eligible patients in our cohort. Mean treatment length was 2.9±2.4 years, with 59% of patients on Maximum Tolerated Dose. The online survey had a response rate of 45% and indicated good adherence (over 80%) in 93% of the respondents. Analysis of laboratory data suggested that 35% of patients had HbF levels above 20%, 38% had neutrophil counts below 3*10³/µL. MPR was above 80% in 52% of cases. HbF levels showed a modest but significant positive correlation with MPR (r2=0.32, p=0.01), but correlated more strongly with other laboratory markers such as neutrophil count (r²=0.45, p<0.001) and MCV (r²=0.4, p=0.002). In multiple regression analysis models, HbF levels were significantly and positively influenced by length of treatment (p=0.004) and escalation to MTD (p=0.02), and were strongly correlated with lower hospitalisation rates (p=0.006). Similarly, neutrophil levels were significantly negatively influenced length of treatment (p=0.04) and μτD (p=0.01) and were inversely correlated with lower hospitalization rates (p=0.02). Regression analysis results for variables that influence HbF and Neutrophil counts are shown in table 1. Starting hydroxycarbamide for clinically symptomatic sickle cell background was significantly linked with lower HbF levels (p=0.03) and higher neutrophil counts. Age, gender, and hydroxycarbamide formulation type did not appear to have a significant influence on HbF levels, neutrophil counts, or MPRs. Conclusion Patient-reported adherence rates were generally higher than adherence assessed by laboratory markers and MPRs. Further research and qualitative interventions are needed to measure and improve adherence to hydroxycarbamide, particularly focusing on patients who start this for clinically symptomatic sickle cell complications, those who are not escalated to MTD, and those in the early stages of treatment. These efforts are crucial in improving outcomes, including reducing hospitalization rates. Reference Reddy PS, Cai SW, Barrera L, King K, Badawy SM. Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents. Ann Med. 2022 Dec;54(1):683–693. doi: 10.1080/07853890.2022.2044509. PMID: 35234095; PMCID: PMC8896206.