The multiregional Italian Thalassemia Registry: patient’s population changes and related iron

chelation approach

Laura Mangiarini1

R. Padula1, D. Bonifazi1, G. Del Vecchio2, P. Baiardi3

1Consorzio per Valutazioni Biologiche e Farmacologiche, Pavia (Italy) 2U.O. Pediatria "Federico Vecchio"A. O. U. Consorziale Policlinico di Bari (Italy)3Fondazione Salvatore Maugeri, Pavia (Italy)

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

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

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

Females Males Global

Gender ( %) 999 (52.6%) 900 (47.4%) 1899

Age :average ± SD

median (range)31.31±11.3233 (0,1-71)

29.41±11.1531 (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 yearsThe 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

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

combined therapy 21,70%

no therapy1,20%

DFO24,10%

DFP20,30%

DFX32,70%

53% of patients is under treatment with an oral chelator45,80% of patients is under treatment with DFO (monotherapy or combined)

Iron chelation in Italy

Paediatrics Adults0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Combined 3,80%

Combined 24,40%

DFO 24,30%

DFO 26,20%

DFP 11,40%

DFP 21,90%

DFX58,60%

DFX 29,40%

Iron chelation approach in paediatrics vs adults

2-5 years 6-11 years 12-17 years 18-25 years 26-35 years 36-45 years >45 years0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

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 ofiron chelation therapy

DFOCombinedDFPDFX

2-5 years 6-11 years 12-17 years 18-25 years 26-35 years 36-45 years >45 years0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

Adult patients are equally distributed among the therapeutic optionsDFO remains the first therapeutic choice for patients >45

Distribution ofiron chelation therapy

DFOCombinedDFPDFX

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 = never1 = true for less than 30% of my patients2 = true for 30 -60% of my patients3 = true for > 60% of my patients

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

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

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

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