Effectiveness of Hydroxyurea in Patients with Sickle Cell Disease in Ghana: A Population-Level, Healthcare Facilities-Based Study

Introduction: Sickle cell disease (SCD) is a major cause of morbidity and premature deaths in sub-Saharan Africa (SSA) (GBD 2021 SCD collaborators. Lancet Haematol 2023). However, clinical care of individuals living with SCD, including access-to-medicines, has largely been neglected in the region. In 2019, the Sickle Cell Foundation of Ghana, Ghana Ministry of Health, Ghana Health Services, and Novartis initiated a public-private partnership to address priority aspects of SCD management through a holistic approach involving access to hydroxyurea (HU), newborn screening capabilities, and other health systems strengthening activities. The University of Ghana was subsequently commissioned to conduct monitoring and evaluation (M&E) of selected program components.

Aim: To evaluate the effectiveness of the HU program in Ghana (“Ahodwo Program”) with specific focus on biomarkers, clinical outcomes, and health-related quality of life (HRQoL).

Methods: The study design was a mixed-methods approach incorporating quantitative and qualitative research (Moore et al. BMJ 2015). Clinical data obtained from a HU management mobile application (designed specifically for the Ahodwo program) and from patient hospital records were used to evaluate biomarkers and clinical outcomes. Data describing HRQoL were obtained from interviews with patients and parents/caregivers in 11 SCD centers. Statistical measures were used to describe quantitative and categorical indicators, and standard regression models quantified the impact of therapy on biomarkers. The study was approved by ethical review boards governing the participating institutions.

Results:Data from 1,549 patients enrolled in the program from September 2019 to July 2023 were available through the HU management app. Regression analyses demonstrated that HU therapy led to a significant average increase in hemoglobin levels (Hb) by 0.55g/dL (95% Confidence Interval [CI]: 0.49 to 0.61; P<0.001) compared to pre-treatment levels. The number of patients that achieved Hb of ≥10 g/dL also increased by 9.2 percentage points [95% CI: 7.58 to 10.83; P<0.001]. The impact of HU on Hb was higher among pts aged >16 years (0.61g/dL [95% CI: 0.52 to 0.69; P<0.001]) vs ≤16 years (0.52g/dL [95% CI: 0.44 to 0.60; P<0.001]), and among male (0.62g/dL [95% CI: 0.53 to 0.70; P<0.001]) vs female (0.48g/dL [95% CI: 0.40 to 0.57; P<0.001]). HU therapy led to an increase in the mean corpuscular volume by ([7.07 {95% CI: 6.47 to 7.68}] x10⁹/L; P<0.001]) and reduction in the absolute neutrophil count ([-1.15 {95% CI: -1.28 to -1.01}] x10⁹/L; P<0.001), platelets (-44.92 [95% CI: -52.38 to -37.46; P<0.001]), red blood cells ([-0.14 {95% CI: (-0.18 to -0.10}] x10¹²/L; P<0.001), and white blood cells ([-1.63 {95% CI: -1.86 to -1.40}] x10⁹/L; P<0.001), vs pre-treatment period. HbF levels and reticulocyte counts were not measured.

Persons with SCD taking HU (N=600 total; 186 were enrolled in the Ahodwo program) were interviewed from April to November 2023. The incidences of blood transfusion in adults and pediatric patients reduced by 77% and 66%, sickle cell crises by 37% and 65%, rates of hospitalization by 63% and 64%, and episodes of malaria by 42% and 59%, respectively (all, P<0.001). Data revealed positive impact of HU therapy on overall HRQoL effects among adult and pediatric patients (improvement by 24% and 44%, respectively), observed as improvements in physical, emotional, social, school-related functioning, and pain episodes (all, P<0.01).

Conclusion:To our knowledge, this is the largest effectiveness study of HU in Africa outside of a controlled trial. The Ahodwo program demonstrated significant benefits for pediatric and adult patients with SCD as measured by biomarkers, clinical outcomes, and HRQoL. In 2022, the Ghana government announced coverage of HU through its National Health Insurance Scheme. Lessons learned through the Ahodwo program have implications for further efforts in Ghana and may be applicable to other countries in Africa where SCD is highly endemic.

Spector:Novartis Biomedical Research: Current Employment, Current holder of stock options in a privately-held company. Egbujo:Novartis Pharmaceutical Corporation: Current Employment, Current holder of stock options in a privately-held company. Marfo:Novartis: Current Employment.