Update on the use of deferasirox in the management of iron overload

Figures & data

Table 1 Trial design and key efficacy results from the ESCALATOR and EPIC studies

Design	Population	Treatment	Key results
ESCALATOR: Open-label, 1 year^Citation24	Pediatric (≥2 years) and adult patients with β-thalassemia, n = 237 (n = 233 in extension study)	Deferasirox 20 mg/kg/day* (initial dose); dose adjustments in steps of 5–10 mg/kg/day based on serum ferritin and safety markers	• After 1 year: 57% of patients had treatment success (P = 0.016)^† Mean reduction in LIC: 3.4 mg Fe/g dw (P < 0.001) Proportion of patients with LIC < 7 mg Fe/g dw had risen from 9.9% at baseline to 26.2% In patients whose therapeutic goal was reduction, significant decrease in serum ferritin (−517 mg/mL; P < 0.001)
Subsequent extension study of at least 1 additional year^Citation25	All patients were previously unsuccessfully chelated with DFO and/or deferiprone
EPIC: Open-label, 1-year^Citation26	Pediatric (≥2 years) and adult patients with β-thalassemia, MDS, DBA, SCD, AA and other rare anemias, n = 1744	Deferasirox 10–30 mg/kg/day (initial dose dependent on blood transfusion frequency); dose adjustments in steps of 5–10 every 3 months based on serum ferritin and safety markers	• At end of study: Proportion of patients with LIC < 7 mg Fe/g dw had risen to 44.4%. Further decreases in LIC and serum ferritin observed • Significant reduction in serum ferritin from baseline in overall population (−264 ng/mL; P < 0.0001), reflective of dosage adjustments and ongoing iron intake • Significant reduction in serum ferritin in each disease cohort

Abbreviations: AA, aplastic anemia; DBA, Diamond-Blackfan anemia; DFO, deferoxamine; dw, dry weight; LIC, liver iron concentration; MDS, myelodysplastic syndromes; SCD, sickle cell disease.

Figure 1 Mean liver iron concentration (LIC) and median serum ferritin at 1 year and end of study. Reproduced with permission. Taher A, El-Beshlawy A, Elalfy M, et al. Haematologica. 2009;94(Suppl 2):abstr 209.²⁵ Obtained from Haematologica/the Hematology Journal website http://www.haematologica.org with kind permission of the Ferrata Storti foudation, Pavia, Italy.

Figure 2 Mean dose and median serum ferritin during long-term deferasirox treatment in patients with β-thalassemia.²⁸

Figure 3 Median change from baseline in serum ferritin in patients enrolled in the EPIC study.²⁶

Table 2 Efficacy of deferasirox across various transfusion-dependent anemias: data from the EPIC trial

	β-thalassemia major (n = 937)^Citation30	MDS (n = 341)^Citation31	AA (n = 116)^Citation32	Rare anemias (n = 43)^Citation33	DBA (n = 14)^Citation34
Baseline, ng/mL*	3157	2730	3254	3161	2289
Change at 1 year, ng/mL*	−129	−253	−964	−832	−790
P value	0.0007	0.0019	0.0003	0.0275	0.0121
Deferasirox dose, mg/kg/day**	24.2 ± 5.6	19.2 ± 5.4	17.6 ± 4.8	18.6 ± 5.6	21.0 ± 4.8

* Serum ferritin data are presented as median;

** Dose data are presented as mean ± SD.

Abbreviations: AA, aplastic anemia; DBA, Diamond-Blackfan anemia; MDS, myelodysplastic syndromes.

Figure 4 The effect of deferasirox on the mean cardiac T2* by baseline T2* in patients A) with cardiac iron overload; B) with normal cardiac levels.^41,42

Figure 5 Mean labile plasma iron (LPI) taken pre-administration and 2 hours post-administration of deferasirox reproduced with permission. Daar S, Pathare A, Nick H, et al. Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia. Eur J Haematol. 2009;82(5):454 457.⁶⁴ © Wiley-Blackwell 2009.

*Versus pre-administration at baseline.

LPI data are from 13 patients except ^†n = 11 ^‡n = 12 due to lost samples.

Table 3 Most common drug-related adverse events during a median 4.5-year treatment period with deferasirox in 472 patients with β-thalassemia²⁸*

Adverse event	Frequency, n (%)
Abdominal pain	62 (13.1)
Nausea	55 (11.7)
Diarrhea	40 (8.5)
vomiting	32 (6.8)
Rash	23 (4.9)

* Pooled data from core and extension phases of 4 pivotal studies.

Figure 6 Overall treatment satisfaction with iron chelation therapy in patients previously treated with deferoxamine (DFO). Reprinted from Clinical Therapeutics. Cappellini MD, Bejaoui M, Agaoglu L, et al. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia. Clin Ther. 2007;29(5):909 917⁷⁸ with permission from Excerpta Medica, Inc.

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