1. The multiregional Italian Thalassemia Registry: patient’s population changes and related iron chelation approach Laura Mangiarini 1 R. Padula 1, D. Bonifazi 1, G. Del Vecchio 2, P. Baiardi 3 1 Consorzio per Valutazioni Biologiche e Farmacologiche, Pavia (Italy) 2 U.O. Pediatria "Federico Vecchio"A. O. U. Consorziale Policlinico di Bari (Italy) 3 Fondazione Salvatore Maugeri, Pavia (Italy)

2. FACTS In Italy 4,000-6000 affected Transfusion => iron overload => iron chelation therapy Iron overload monitoring => ferritin, hepatic and cardiac MRI  -Thalassemia– Mediterranean Anemia in Italy

3.  The “Inter-regional Network for Thalassemia” was promoted by the Italian MoH in 2010.  A registry of thalassemia patients was set up to provide a flexible platform for the assessment of patients’ characteristics and disease management, utilization of chelating agents, treatment outcome, AEs rate, methodologies for iron deposition evaluation and cost of therapies.  Data were used to perform a prevalence study aimed at:  evaluating the demographic characteristics of the study population 11 and 5 years respectively after the introduction of the two oral chelators DFP and DFX  describing the current management of iron overload in a large cohort of different age subsets of patients. The Italian Registry of Thalassemia patients

4. all together => 1899 patients (adults and paediatrics) in 31 centri: 1100 NUMBERS 16 regions 60 clinical centres 1-150 patients each 36 centres: paediatric and adult patients 22 centres: only adults 2 centres: only paediatrics The Italian Registry of Thalassemia patients in 2011

5. FemalesMalesGlobal Gender ( %)999 (52.6%)900 (47.4%)1899 Age : average ± SD median (range) 31.31±11.32 33 (0,1-71) 29.41±11.15 31 (0,7-69) 30,40 ± 11,29 32 (0,1-71) Paediatrics (%)127 (48.3%)136 (51,7%)263 Average age of patients is 30 years The progressive increase of the global mean age is determined by the sistematic use of iron chelating agents Demographic data of patients participating to the study

6. 13,8% are paediatrics (263 patients) 8,0% of the Italian thalassemic population is younger than 12 years Patients distribution stratified by age and gender

7. no therapy 1,20% DFO 24,10% DFP 20,30% DFX 32,70% 53% of patients is under treatment with an oral chelator 45,80% of patients is under treatment with DFO (monotherapy or combined) Iron chelation in Italy

8. Combined 3,80% Combined 24,40% DFO 24,30% DFO 26,20% DFP 11,40% DFP 21,90% DFX 58,60% DFX 29,40% Iron chelation approach in paediatrics vs adults

9. Over 50% of children < 5 years is with DFX, DFO is used by 37% The subset 12-17 years is the highest user of oral chelators (72.8%) Distribution of iron chelation therapy DFO Combined DFP DFX

10. Adult patients are equally distributed among the therapeutic options DFO remains the first therapeutic choice for patients >45 Distribution of iron chelation therapy DFO Combined DFP DFX

11. Reasoning leading to the selection of iron chelation therapy A structured interview was conducted with a subgroup (15) of the participating clinical centres aimed at exploring the medical reasons for: changing from the parenteral to an oral iron chelation therapy changing from the monotherapy to a combination therapy The interview was based on a multiple choice questionnaire and to each answer a score 0 => 3 was attributed: 0 = never 1 = true for less than 30% of my patients 2 = true for 30 -60% of my patients 3 = true for > 60% of my patients

12. Median score 1) What are the reasons leading you to switch your patient from DFO to DFP? a) Poor compliance to DFO 3 b) Intolerance to DFO 0 c) Cardiac iron overload 2 d) Moderate AEs 0 e) Severe Aes 0 f) Other 0 2) What are the reasons leading you to switch your patient from DFO to DFX? a) Poor compliance to DFO 3 b) Intolerance to DFO 0 c) Cardiac iron overload 0 d) Moderate AEs 0 e) Severe Aes 0 f) Other 0 3) What are the reasons leading you to switch your patient to a combined therapy DFO/DFP? a) Cardiac iron overload 3 b) Other 0 4) What are the reasons leading you to switch your patient to a sequential therapy DFO/DFP? a) Poor compliance to DFO 2 b) Cardiac iron overload 1 c) Potential reduction of side effects 1 d) Other 0 5) The change of therapy is:a) Suggested by the physician 3 b) Requested by the patient 1 c) Shared 0 Reasoning leading to the selection of iron chelation therapy

13. The introduction of the oral chelators has progressively changes the prescription habits in children and young patients: DFO is progressively excluded from the chelation treatment in young patients DFX is the preferred therapeutic approach because well accepted DFP is acknowledged for depleting cardiac iron Reasoning leading to the selection of iron chelation therapy

14. Conclusions To date, in patients > 45 years the elective therapy remains DFO or DFP (as monotherapy or combination therapy): there is little inclination in changing therapy when efficacious => the therapeutic effect is predominant on the route of administration The availability of alternative therapeutic options has sensibly increased the survival of the thalassemic patient

15. Conclusions There is no perfect iron chelating agent but three chelators are available with different pharmacological profile: => it is critical to make them available also for paediatric patients in order to increase the possibility to provide the most suitable treatment for each patient in terms of safety, efficacy and compliance => it is important to search for new chelators