The Increased Burden of Sickle Cell Disease in Italy: Findings from the Greatalys (Generating Real world Evidence Across ITALy In SCD) Study
Authors: de Franceschi Lucia , Forni Gian Luca , Castiglioni Chiara , Condorelli Claudia , Valsecchi Diletta , Premoli Eleonora , Perrone Valentina , Degli Esposti Luca , Fiocchi Carina Andrea 
Published: November 2021

Abstract
Introduction. Sickle Cell Disease (SCD) is an evolving public health issue with a significant impact on patient survival, quality of life and costs for health systems also in Italy, a multiethnic country where epidemiology has deeply changed. We present final results from the GREATalyS study that aimed to better understand the SCD burden in Italy in terms of prevalence, clinical features, treatments and resource consumption in the clinical practice setting.
Methods. Retrospective observational analysis of administrative databases for health resources consumption from a representative sample of Region/Local Health Units in Italy, covering approximately 15.3 million inhabitants. All patients with ≥1hospitalization (outside Emergency Room, ER) with main or secondary discharge diagnosis of SCD (with/without crisis) identified by ICD-9-CM codes were included between January-2010 to December-2017 (up to December 2018 for epidemiologic analysis). Prevalence of SCD in 2018 was projected to the Italian population. Patients were followed-up from the first diagnosis identified within the inclusion period (index date) to death or end of data availability. Treatments and healthcare resource consumption were evaluated on patients with at least 1 year of data availability before and after index date. SCD treatments were classified as SCD-specific, SCD-related, SCD-complication-related. Both day hospitals and ordinary hospitalizations were evaluated. Vaso-occlusive crisis (VOCs) (identified by hospitalization discharge diagnosis for SCD with crisis) and main SCD organ complications were assessed during follow-up. Mean annual healthcare resource costs were analyzed during follow-up according to the NHS perspective in terms of overall treatments, all-cause hospitalizations and out-patients services.
Results. SCD prevalence in 2018 was 13 cases per 100,000 inhabitants. Prevalence projected to Italian population estimated in total 7,977 SCD patients in Italy in 2018 (of whom 1,690 and 6,287 were &lt;18 and ≥18 years, respectively, figure 1): 1,279 were estimated with crisis, 5,894 without crisis and 804 unspecified. The study population included in the analysis comprised 1,816 patients (mean age 43.8 years, 58.4% female). Of them, 74.3% were without diagnosis of crisis, 16.1% with crisis, and 9.6% unspecified. Hematology and general medicine were the most frequent admission/discharge hospital departments for a subcohort of patients for which these data were available. During the first year of follow-up (index date included), 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3 and 11.1% had ≥4, in the second year 44% had at least one hospitalization, while in the third and fourth years 38.2% and 35.8%, respectively (table 1). During the available follow-up period (mean years±SD: 4.9±2.2) the average length of hospitalization stays (table 2) was around 8 days (ordinary hospitalizations) and 130 days (day hospitals). Proportion of patients with a VOC or one SCD complication was 3.7% and 15.2%, with 2 was 2.3% and 6.2% and with ≥3 was 7.7% and 12.8%, respectively. The mean annual number of SCD specific drugs was 0.6±2.7, of SCD related drugs was 3.2±4.5 and of SCD-complications-related drugs was 8.6±10.5. Antibacterials were the more frequently prescribed drugs (53-63%), followed by drugs for acid related disorders (35-48%) and antithrombotic agents (25-34%). Considering all available follow-up, mean annual number of all drugs was 14.9, of hospitalizations was 1.1 and of outpatient specialist services 5.3. Total mean annual cost per patient was €7,917 (€2,201 for prescribed drugs, €3,320 for hospitalizations, and €2,397 for outpatient specialist services, figure 2).
Conclusions. This Italian real-world study may have revealed a SCD sub-population probably not noticed yet to SCD centers of reference, and still probably underestimated since ER flows were not present. Similarly, also VOC could be underestimated as only most severe episodes requiring hospitalization were captured. Proportion of patients with antithrombotic agents might be an indicator of the underlying multiorgan complications. The present data describe an SCD population with high resource utilization and heavy economic burden and warrants further efforts to increase an earlier patient identification that could lead to a timely and comprehensive treatment with less SCD-related complications.
Figure 1 Figure 1.

Disclosures
Forni: Bluebirdbio: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Castiglioni: Novartis Farma SpA: Current Employment. Condorelli: Novartis Farma SpA: Current Employment. Valsecchi: Novartis Farma SpA: Current Employment. Premoli: Novartis Farma SpA: Current Employment. Fiocchi: Novaris Farma SpA: Current Employment.