Thalassemia is a group of genetically inherited hemoglobin (Hb) disorders characterized by reduced synthesis of the b-globin chain and a sub-sequent imbalance in the a/b-globin chain ratio that results in chronic hemolytic anemia. The severity of clinical phenotype is used to distinguish this heterogeneous disease in two main subtypes: Thalassemia Major (TM) and Thalassemia Intermedia (TI). Iron overload is mostly due to increased intestinal absorption because of chronic anemia. Transfusions, in contrast with what happens in TM, have a minor role in the development of iron overload. However, although 1-year data from the phase 2, prospective, randomized, double-blind, placebo-controlled trial and 1-year extension results from the THALASSA study assessing the efficacy and safety of deferasirox in TI patients with iron overload have been reported, no data, during randomized trials, have been so far published on Deferiprone (DFP) treatment (Taher et al Blood 2012 and Ann Hematol 2013) Adult patients with TI were randomly assigned in permuted blocks of 10 with a ratio 1:1 to DFP at 75 mg/kg/day for 7 d/week divided into three oral daily doses (DFP-group) or DFO by sc infusion (8–10 h) at 50 mg/kg per day for 5 d/week (DFO-group). The study was designed to detect an improvement in decreasing mean serum ferritin levels in each of the treated-groups from the initiation of therapy to each year (from year 1 to year 5) with a significance level of 5% and 80% power. The planned number of subjects was between 40 and 100 (Rochon Biometrics 1991). The primary endpoint was the treatment efficacy evaluated as change from the baseline value in serum ferritin levels during the 5 years assessed using a linear mixed-effects model (LMM, Laird-Ware Biometrics 1982) where we assumed the patient effect (given by the intercept terms for each patient) as random effect, while the treatment effect (treat), the time effect (time), the treatment-by-time interaction effect (treat×time), and the total transfusions in ml (tot TX) as fixed effects. Secondary endpoints were safety and survival analysis at 5-years evaluated considering the number of advers events and Kaplan-Meir curves respectively. Overall 88 patients, observed at 12 SoSTE centers in Italy between January 2001 and May 2011, were randomized (47 DFP-group and 41 DFO-group). There were no differences observed at baseline between the two randomized groups in clinical and haematological findings. The regression coefficient of time suggested that there was a linear decrease over time in the mean serum ferritin levels in both treatment-groups even if the p-value was very close to the statistical significance (Coeff. -88.4, 95% CI (-182.4; 5.6), p-value =0.065). However, the mean serum ferritin levels did not seem to be significantly different between the two treatment-groups over time (Coeff. -77.4, 95% CI (-231.7; 77.1), p-value=0.326 ). The effect of total blood transfusion on serum ferritin levels was not statistically significant (Coeff. 0.06, 95% CI (-0.01; 0.1), p-value=0.100). The estimated profiles of serum ferritin levels in the two groups were represented in Figure I. Agranulocytosis was reported in 4 case of DFP versus no cases of DFO group, respectively (p-value=0.118). Neutropenia was statistically significant different between the two groups DFP (6 (12.5%) versus no cases in DFO , p-value=0.027). Kaplan-Meier survival probability curves for the two treatment groups are shown in Figure II, and the log-rank test did not show any statistically significant difference in the survival between the two groups (p-value=0.36). In conclusion, these findings suggest as DFP shows same effectiveness and survival probability versus DFO with controlled safety profile. Therefore, these results support the possibility of using this drug in TI patients in which DFO and Deferasiorx is contraindicated. Figure I: Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model. Figure I:. Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model. Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36). Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36). Disclosures No relevant conflicts of interest to declare.

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Introduction In thalassemia major (TM) three iron chelators in monotherapy are available to treat chronic iron overload due to blood transfusions: subcutaneous desferrioxamine (DFO) introduced in the 1960s, oral deferiprone introduced in 1999 and oral deferasirox (DFX) licensed in 2006. Nowadays pharmacoeconomics analysis are frequently required by the health authorities due to the actual economic crisis. The aim should be to ensure to the whole community the sustainability for health care of proved quality. The objective of this study was to determine the costs of the three chelators in monotherapy in a cohort of 193 TM patients followed prospectively for 18 ± 3 months. Methods Within the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated prospectively 193 TM patients who had been received one chelator alone between the 2 Magnetic Resonance scans and we calculated the direct costs (drug, administration and monitoring) for each patient treated with DFX, DFO and DFP. We used the cost values for the year 2007. For the drugs we considered the cost ex-factory. For the oral chelators the administration cost was considered null. For the DFO we calculated the costs for the administration (pump, infusion set, syringes and gauzes) using the tariffs applied in Veneto Region, Italy. For the monitoring costs we considered the exams suggested in the technical sheet for each drug; we considered the tariffs by the Veneto Region, Italy. In Italy Veneto Region was proved to be one of the most upright region in the health costs management. In the analysis we considered the drug cost for the standard dosage reported in the technical sheet: 40 mg/kg/d for DFO, 75 mg/kg/d for DFP  and 30 mg/kg/d for DFX. Based on the mean weight of the patients we referred the drug cost to a patient of 60 Kg. Results In the clinical practice the dose of DFX was 26±7 mg/kg/d, DFP was 73±13 mg/kg/d and DFO was 41±6 mg/kg for 5.5 d/wk. Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P=0.6). The cost/mg was € 0.006 for Generic DFO, € 0.003 for Ferriprox® (DFP) and € 0.047 for Exjade® (DFX). For 18 months of treatment the total costs for DFO were € 10.465,8 (administration and monitoring costs € 3.965,1 + drug cost 6.500,7), for DFP were € 8.292,9 (administration and monitoring costs € 460,8 + drug cost 7.832,2), for DFX were € 46.461,2 (administration and monitoring costs € 211,14 + drug cost 46.249,8). The details about the administration and monitoring costs for DFO, DFP and DFX are reported in the table. Conclusion In this analysis, for managing chronic iron overload the direct costs for oral DFP appeared to be the less expensive. The limit of this study is that a cost-utility analysis taking into account efficacy, adverse events and route of administration was not performed. Disclosures: Pepe: ApoPharma inc, Novartis, Chiesi: Speakers Bureau.

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Thalassemia is a Mendelian inherited blood disease caused by α- and β-globin gene mutations, known as one of the major health problems of Mediterranean populations. Here, we examined the distribution of α- and β-globin gene defects in the Trapani province population. A total of 2,401 individuals from Trapani province were enrolled from January 2007 to December 2021, and routine methodologies were used for detecting the α- and β-globin genic variants. Appropriate analysis was also performed. Eight mutations in the α globin gene showed the highest frequency in the sample studied; three of these genetic variants represented the 94% of the total α-thalassemia mutations observed, including the −α3.7 deletion (76%), and the tripling of the α gene (12%) and of the α2 point mutation IVS1-5nt (6%). For the β-globin gene, 12 mutations were detected, six of which constituted 83.4% of the total number of β-thalassemia defects observed, including codon β039 (38%), IVS1.6 T > C (15.6%), IVS1.110 G > A (11.8%), IVS1.1 G > A (11%), IVS2.745 C > G (4%), and IVS2.1 G > A (3%). However, the comparison of these frequencies with those detected in the population of other Sicilian provinces did not demonstrate significant differences, but it contrarily revealed a similitude. The data presented in this retrospective study help provide a picture of the prevalence of defects on the α and β-globin genes in the province of Trapani. The identification of mutations in globin genes in a population is required for carrier screening and for an accurate prenatal diagnosis. It is important and necessary to continue promoting public awareness campaigns and screening programs.