Prevalence and cost of sickle cell disease in France: real-world analysis using data from the Echantillon Généraliste des Bénéficiaires.

Sickle cell disease (SCD) is a genetic disorder of the hemoglobin resulting in chronic anemia, hemolysis, and vaso-occlusions. Its treatment mostly relies on hydroxycarbamide, transfusions, and stem cell transplantation. This study aimed at describing the epidemiology and management of SCD in adolescent and adult patients in France. This was a retrospective study performed among SCD patients aged ≥12 years between 2016 and 2018 and controls. SCD patients were matched on a 1:3 ratio with a group of individuals with no diagnosis of SCD, referred as control group. The matching of SCD patients and controls was a direct matching based on age, sex, CMU-c status (which corresponds to free-of-charge complementary coverage for people with low resources) and geographical region of residence. SCD patients and their matched controls were followed-up for the same amount of time by adjusting controls' follow-up period to that of the associated patients. This study used claims data from the French representative 1/97th sample of health data system. The main outcomes were the patients' characteristics and treatments received, healthcare consumptions and related costs among SCD cases and controls. Between 2016 and 2018, 151 patients with ≥6 months of follow-up were identified out of the total population of 732,164 individuals. SCD prevalence extrapolated to the entire population [95% CI] was 19,502 [19,230, 19,778] in 2018. The median (Q1-Q3) age at inclusion date was 37.0 (25.0-48.0) years, with 69.5% of patients being female. The mean (SD) reimbursed cost over follow-up was €24,310 (89,167), mostly represented by hospitalization costs accounting for €21,156 (86,402). A switch in SCD management was observed with age, as younger patients presented more frequent hospitalizations and acute procedures, while older ones had more frequent medical visits and paramedical care. Mean (SD) annual costs were €25,680 (91,843) and vs. €3,227 (23,372) for patients and controls, respectively (p < 0.001), representing an extra cost of almost €150 million over the entire SCD population. This study highlighted the important costs related to SCD and the related medical need with treatment alternatives, which could be filled by the emergence of new therapies.

Epidemiology and disease burden of sickle cell disease in France: A descriptive study based on a French nationwide claim database.

CONTEXT: Sickle cell disease (SCD) is a severe hematological disorder. The most common acute complication of SCD is vaso-occlusive crisis (VOC), but SCD is a systemic disease potentially involving all organs. SCD prevalence estimates rely mostly on extrapolations from incidence-based newborn screening programs, although recent improvements in survival may have led to an increase in prevalence, and immigration could account for a substantial number of prevalent patients in Europe. The primary objective of this study was to estimate SCD prevalence in France. METHODS: A cross-sectional observational study was conducted using a representative sample of national health insurance data. SCD patients followed up in France between 2006 and 2011 were captured through hydroxyurea reimbursement and with the International Classification of Diseases (ICD-10) SCD specific code D570.1.2, excluding code D573 (which corresponds to sickle cell trait (SCT)). Nevertheless, we assumed that ICD-10 diagnosis coding for inpatient stays could be imperfect, with the possibility of SCT being miscoded as SCD. Therefore, prevalence was analyzed in two groups of patients [with at least one (G1) or two (G2) inpatient stay] based on the number of SCD-related inpatient stays in the six-year study period, assuming that SCT patients are rarely rehospitalized compared to SCD. The prevalence of SCD in the sample, which was considered to be representative of the French population, was then extrapolated to the general population. The rate of vaso-occlusive crisis (VOC) events was estimated based on hospitalizations, emergencies, opioid reimbursements, transfusions, and sick leave. RESULTS: Based on the number of patients identified for G1 and G2, the 2016 French prevalence was estimated to be between 48.6 per 100,000 (G1) or 32,400 patients and 29.7 per 100,000 (G2) or 19,800 patients. An average of 1.51 VOC events per year were identified, with an increase frequency of 15 to 24 years of age. The average annual number of hospitalizations was between 0.70 (G1) and 1.11 (G2) per patient. Intensive care was observed in 7.6% of VOC-related hospitalizations. Fewer than 34% of SCD patients in our sample received hydroxyurea at any point in their follow-up. The annual average cost of SCD care is €5,528.70 (G1) to €6,643.80 (G2), with most costs arising from hospitalization and lab testing. CONCLUSION: Our study estimates SCD prevalence in France at between 19,800 and 32,400 patients in 2016, higher than previously published. This study highlights the significant disease burden associated with vaso-occlusive events.

Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404).

BACKGROUND: Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. DESIGN: DREPAGREFFE (NCT01340404) is a multicenter, prospective trial enrolling SCA children younger than 15years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥200cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. OBJECTIVES: To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. DISCUSSION: DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.