Cost-effectiveness of hydroxyurea for sickle cell anemia in a low-income African setting: a model-based evaluation of two dosing regimens

Background and Objective: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efcacy suitable for SSA; however, no one has quantifed the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-efectiveness of hydroxyurea as a fxed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. Methods: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-efectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3Results: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fxed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1–11.4) units of blood per patient, compared with 9.1 (95% CI 9.0–9.2) units of blood per patient at the fxed-dose alternative. Conclusions: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fxed dose regimen, treatment dosing at MTD is likely to be a cost-efective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of lif

132:poster Cost-effectiveness of using hydroxyurea to treat sickle cell anemiain uganda: a model-based comparison of two dosing regimens

Background Recognition of the burden of sickle cell anaemia (SCA) in sub-Saharan African (SSA) countries is increasing, with few therapies available for clinical management. Hydroxyurea is the only disease-modifying therapy that has proven feasible and clinically efficacious in low-income countries in SSA; however, the health economic implications of its use in this region have not been quantified. Thus, we examined the incremental cost-effectiveness of hydroxyurea given as a fixed-dose regimen or at the maximum tolerated dose (MTD). Methods We estimated the cost of outpatient treatment at a specialized sickle cell clinic in Kampala, Uganda, from a provider’s perspective. These estimates were used in a discrete-event simulation model to project mean costs (US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 ml units). We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3 For Ugandan patients under the age of 18, we predicted that hydroxyurea at the MTD would avert an expected 1.38 DALYs and save US$ 111 per patient compared to standard care, while hydroxyurea at a fixed dose would avert 0.81 DALYs per patient at an incremental cost of US$ 21. Additionally, we predicted that the fixed-dose alternative would save 9.2 (95% CI 9.0–9.3) units of whole-blood equivalents per patient, while the MTD strategy saved 11.3 (95% CI 11.1–11.4) units of blood per patient

Effect of hydroxyurea treatment on body composition in children with sickle cell anemia in Uganda using bioelectrical impedance analysis (BIA)

Introduction: Children with sickle cell anemia (SCA) experience severe illness and risk of malnutrition in sub-Saharan Africa. Treatment with hydroxyurea (HU) decreases SCA complications. In high-income regions, hydroxyurea also improves pediatric growth and overall quality of life. We assessed the effects of hydroxyurea on growth and body composition of children with SCA in Uganda. Methods: This study was nested in an open-label, single-arm pediatric clinical trial of hydroxyurea 20-30mg/kg/day for prevention of neurological and cognitive impairment. In all, 267 study participants with SCA, ages 3-9 years, initiated hydroxyurea treatment at the Mulago Hospital SCA Clinic in Kampala, Uganda. Anthropometric measurements (weight, height) were obtained at enrollment and at month 18 of therapy; age- and sex-specific z-scores were assigned, per World Health Organization (WHO) international standards. Non-invasive bioelectric impedance analysis (BIA), was used to estimate total body fat mass (FM) and fat-free mass (FFM) at both timepoints. A control sample of110 siblings/family members without SCA, aged 3-12 years, established local z-scores for BIA assessments. Results: Among SCA participants and controls, 50.6% and 57.3% were female, respectively. Mean age was younger foror the SCA sample: 5.1±0.1 and 7.1±0.3 years ( p Conclusion: Hydroxyurea therapy in children with SCA increased hemoglobin yet did not reduce the proportion with wasting after 18 months. Nonetheless, treatment led to significantly improved FM and FFM to near normal levels. These results suggest that hydroxyurea therapy may play a crucial role in enhancing body composition of children with SCA in the region. The ongoing hydroxyurea trial will enable assessment of longer-term impact on health-related growth and body composition in children with SCA in Uganda

Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa

BACKGROUND Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown. METHODS In a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day). The primary outcome was a hemoglobin level of 9.0 g or more per deciliter or a fetal hemoglobin level of 20% or more after 24 months. Secondary outcomes included the incidences of malaria, vaso-occlusive crises, and serious adverse events. RESULTS Children received hydroxyurea at a fixed dose (94 children; mean [±SD] age, 4.6±1.0 years) or with dose escalation (93 children; mean age, 4.8±0.9 years); the mean doses were 19.2±1.8 mg per kilogram per day and 29.5±3.6 mg per kilogram per day, respectively. The data and safety monitoring board halted the trial when the numbers of clinical events were significantly lower among children receiving escalated dosing than among those receiving a fixed dose. At trial closure, 86% of the children in the dose-escalation group had reached the primary-outcome thresholds, as compared with 37% of the children in the fixed-dose group (P<0.001). Children in the dose-escalation group had fewer sickle cell–related adverse events (incidence rate ratio, 0.43; 95% confidence interval [CI], 0.34 to 0.54), vaso-occlusive pain crises (incidence rate ratio, 0.43; 95% CI, 0.34 to 0.56), cases of acute chest syndrome or pneumonia (incidence rate ratio, 0.27; 95% CI, 0.11 to 0.56), transfusions (incidence rate ratio, 0.30; 95% CI, 0.20 to 0.43), and hospitalizations (incidence rate ratio, 0.21; 95% CI, 0.13 to 0.34). Laboratory-confirmed dose-limiting toxic effects were similar in the two groups, and there were no cases of severe neutropenia or thrombocytopenia. CONCLUSIONS Among children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to that of fixed-dose hydroxyurea, with equivalent safety

Malaria in Children with Sickle Cell Anaemia in Areas with Low, Moderate and High Transmission in Uganda

Background. Few large prospective studies have evaluated burden and outcomes of malaria in children with sickle cell anaemia (SCA) in malaria endemic countries. We evaluated the incidence, complications and outcome of malaria in three cohorts of Ugandan children with SCA in three areas with differing malaria transmission. Methods. Cohort 1 were SCA aged 3-9 years, enrolled in the hydroxyurea therapy for neurological and cognitive protection in Uganda (BRAINSAFE II) trial at Mulago Hospital, a low transmission area, while cohort 2 and 3 aged 6 months to 15 years, were enrolled in the dihydroartemisinin-piperaquine (DP) or sulphadoxine-pyrimethamine (SP) for the chemoprevention of malaria in SCA (CHEMCHA) trial at Jinja Hospital (moderate transmission) and Kitgum Hospital (high transmission). In cohort 1, all received SP for malaria chemoprophylaxis and hydroxyurea at 20-30mg/kg/day, while cohorts 2 and 3, received either DP or SP for malaria chemoprevention, and a proportion (10%) received hydroxyurea in the study. Results. A total of 706 participants were enrolled: 267, 249 and 190 at Mulago, Jinja and Kitgum respectively. The mean age was 6.5 (SD 3.4) years; 5.1 (1.7), 7.9 (4.3) and 6.8 (3.5) years for Mulago, Jinja, and Kitgum respectively. Incidence of malaria was 13 (95% CI 6, 20) per 100 child years in low, 38 (95% CI 26, 51) in moderate and 104 (95% CI 64, 144) in the high transmission area, p<0.001. Adjusting for hydroxyurea treatment, incidence of malaria was 33 (95%CI 14, 52) per 100 child year on hydroxyurea and 51 (95%CI 40, 62) per 100 child years without hydroxyurea, p=0.001. The most common SCA-related complications were anaemia (39.6%, 133/336), and pain (27.7%, 93/336) among children with malaria. Over a period of 1042.8 person years, there were 115 admissions for malaria, with an overall incidence of 11 per 100 child year (95% CI 9, 13), and this differed across sites, p<0.001. Overall, 1.5% (11/706) children died, and 18.2% (2/11) deaths were directly related to malaria infection. Conclusion. Malaria incidence remains high among Ugandan children with SCA, and differs by transmission patterns. Prevention strategies should be strengthened, especially in high transmission areas