Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (>30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.

1.
Viprakasit
V
,
Lee-Lee
C
,
Chong
QT
,
Lin
KH
,
Khuhapinant
A
.
Iron chelation therapy in the management of thalassemia: the Asian perspectives
.
Int J Hematol
.
2009
Nov
;
90
(
4
):
435
45
.
[PubMed]
0925-5710
2.
Rund
D
,
Rachmilewitz
E
.
Beta-thalassemia
.
N Engl J Med
.
2005
Sep
;
353
(
11
):
1135
46
.
[PubMed]
0028-4793
3.
Neufeld
EJ
.
Update on iron chelators in thalassemia
.
Hematology (Am Soc Hematol Educ Program)
.
2010
;
2010
(
1
):
451
5
.
[PubMed]
1520-4391
4.
Food
DA
. http://www.accessdata.fda.gov/drugsatfda˙docs/label/
2010
/021882s010lbl.pdf (accessed 02 September 2011).
5.
European Medicines Agency L
. UK: Exjade:European Public Assessment Report: Summary ofProduct Characteristics. www.emea.europa.eu/humandocs/Humans/EPAR/exjade/exjade.htm (accessed 14 February2008).
6.
Chalmers
AW
,
Shammo
JM
.
Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions
.
Ther Clin Risk Manag
.
2016
Feb
;
12
:
201
8
.
[PubMed]
1176-6336
7.
Dubey
AP
,
Sudha
S
,
Parakh
A
.
Deferasirox: the new oral iron chelator
.
Indian Pediatr
.
2007
Aug
;
44
(
8
):
603
7
.
[PubMed]
0974-7559
8.
Meerpohl
JJ
,
Antes
G
,
Rücker
G
,
Fleeman
N
,
Motschall
E
,
Niemeyer
CM
, et al
Deferasirox for managing iron overload in people with thalassaemia
.
Cochrane Database Syst Rev
.
2012
Feb
;(
2
):
CD007476
.
[PubMed]
1469-493X
9.
Xia
S
,
Zhang
W
,
Huang
L
,
Jiang
H
.
Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials
.
PLoS One
.
2013
Dec
;
8
(
12
):
e82662
.
[PubMed]
1932-6203
10.
Higgins
JP
,
Thompson
SG
,
Deeks
JJ
,
Altman
DG
.
Measuring inconsistency in meta-analyses
.
BMJ
.
2003
Sep
;
327
(
7414
):
557
60
.
[PubMed]
0959-8138
11.
DerSimonian
R
,
Laird
N
.
Meta-analysis in clinical trials
.
Control Clin Trials
.
1986
Sep
;
7
(
3
):
177
88
.
[PubMed]
0197-2456
12.
Taher
AT
,
Porter
JB
,
Viprakasit
V
,
Kattamis
A
,
Chuncharunee
S
,
Sutcharitchan
P
, et al
Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients
.
Am J Hematol
.
2013
Jun
;
88
(
6
):
503
6
.
[PubMed]
0361-8609
13.
Taher
AT
,
Porter
JB
,
Viprakasit
V
,
Kattamis
A
,
Chuncharunee
S
,
Sutcharitchan
P
, et al
Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: the safety profile of deferasirox
.
Eur J Haematol
.
2014
Jun
;
92
(
6
):
521
6
.
[PubMed]
0902-4441
14.
Pennell
D
,
Porter
JB
,
Cappellini
MD
,
Chan
LL
,
El-Beshlawy
A
,
Aydinok
Y
, et al
Efficacy and safety of deferasirox in reducing myocardial siderosis in patients with b-thalassaemia major
.
Haematologica
.
2009
;
•••
:
74
5
.0390-6078
15.
Galanello
R
,
Piga
A
,
Alberti
D
,
Rouan
MC
,
Bigler
H
,
Séchaud
R
.
Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia
.
J Clin Pharmacol
.
2003
Jun
;
43
(
6
):
565
72
.
[PubMed]
0091-2700
16.
Piga
A
,
Galanello
R
,
Forni
GL
,
Cappellini
MD
,
Origa
R
,
Zappu
A
, et al
Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload
.
Haematologica
.
2006
Jul
;
91
(
7
):
873
80
.
[PubMed]
1592-8721
17.
Hassan
MA
,
Tolba
OA
.
Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine
.
Electron Physician
.
2016
May
;
8
(
5
):
2425
31
.
[PubMed]
2008-5842
18.
Pennell
DJ
,
Porter
JB
,
Piga
A
,
Lai
Y
,
El-Beshlawy
A
,
Belhoul
KM
, et al;
CORDELIA study investigators
.
A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA)
.
Blood
.
2014
Mar
;
123
(
10
):
1447
54
.
[PubMed]
0006-4971
19.
Taher
AT
,
Porter
J
,
Viprakasit
V
,
Kattamis
A
,
Chuncharunee
S
,
Sutcharitchan
P
, et al
Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study
.
Blood
.
2012
Aug
;
120
(
5
):
970
7
.
[PubMed]
0006-4971
20.
Nisbet-Brown
E
,
Olivieri
NF
,
Giardina
PJ
,
Grady
RW
,
Neufeld
EJ
,
Séchaud
R
, et al
Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial
.
Lancet
.
2003
May
;
361
(
9369
):
1597
602
.
[PubMed]
0140-6736
21.
Cappellini
MD
,
Cohen
A
,
Piga
A
,
Bejaoui
M
,
Perrotta
S
,
Agaoglu
L
, et al
A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia
.
Blood
.
2006
May
;
107
(
9
):
3455
62
.
[PubMed]
0006-4971
22.
Higgins
JP
,
Thompson
SG
.
Quantifying heterogeneity in a meta-analysis
.
Stat Med
.
2002
Jun
;
21
(
11
):
1539
58
.
[PubMed]
0277-6715
23.
Fisher
SA
,
Brunskill
SJ
,
Doree
C
,
Gooding
S
,
Chowdhury
O
,
Roberts
DJ
.
Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia
.
Cochrane Database Syst Rev
.
2013
Aug
;(
8
):
CD004450
.
[PubMed]
1469-493X
24.
Cappellini
MD
,
Taher
A
.
Long-term experience with deferasirox (ICL670), a once-daily oral iron chelator, in the treatment of transfusional iron overload
.
Expert Opin Pharmacother
.
2008
Sep
;
9
(
13
):
2391
402
.
[PubMed]
1465-6566
25.
Cappellini
MD
,
Porter
J
,
El-Beshlawy
A
,
Li
CK
,
Seymour
JF
,
Elalfy
M
, et al;
EPIC Study Investigators
.
Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias
.
Haematologica
.
2010
Apr
;
95
(
4
):
557
66
.
[PubMed]
0390-6078
26.
Taher
A
,
El-Beshlawy
A
,
Elalfy
MS
,
Al Zir
K
,
Daar
S
,
Habr
D
, et al
Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study
.
Eur J Haematol
.
2009
Jun
;
82
(
6
):
458
65
.
[PubMed]
0902-4441
27.
Taher
A
,
Cappellini
MD
,
Vichinsky
E
,
Galanello
R
,
Piga
A
,
Lawniczek
T
, et al
Efficacy and safety of deferasirox doses of [{GT}]30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload
.
Br J Haematol
.
2009
Dec
;
147
(
5
):
752
9
.
[PubMed]
0007-1048
28.
Wood
JC
,
Kang
BP
,
Thompson
A
,
Giardina
P
,
Harmatz
P
,
Glynos
T
, et al
The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores
.
Blood
.
2010
Jul
;
116
(
4
):
537
43
.
[PubMed]
0006-4971
29.
Pathare
A
,
Taher
A
,
Daar
S
.
Deferasirox (Exjade) significantly improves cardiac T2* in heavily iron-overloaded patients with beta-thalassemia major
.
Ann Hematol
.
2010
Apr
;
89
(
4
):
405
9
.
[PubMed]
0939-5555
30.
Pennell
DJ
,
Porter
JB
,
Cappellini
MD
,
El-Beshlawy
A
,
Chan
LL
,
Aydinok
Y
, et al
Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia
.
Blood
.
2010
Mar
;
115
(
12
):
2364
71
.
[PubMed]
0006-4971
31.
Aydinok
Y
,
Kattamis
A
,
Cappellini
MD
,
El-Beshlawy
A
,
Origa
R
,
Elalfy
M
, et al;
HYPERION Investigators
.
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
.
Blood
.
2015
Jun
;
125
(
25
):
3868
77
.
[PubMed]
0006-4971
32.
Ansari
S
,
Azarkeivan
A
,
Miri-Aliabad
G
,
Yousefian
S
,
Rostami
T
.
Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior
.
Caspian J Intern Med
.
2017
;
8
(
3
):
159
64
.
[PubMed]
2008-6164
33.
Elalfy
MS
,
Adly
AM
,
Wali
Y
,
Tony
S
,
Samir
A
,
Elhenawy
YI
.
Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients
.
Eur J Haematol
.
2015
Nov
;
95
(
5
):
411
20
.
[PubMed]
0902-4441
34.
Shashaty
G
,
Frankewich
R
,
Chakraborti
T
,
Choudary
J
,
Al-Fayoumi
S
,
Kacuba
A
,
Castillo
S
,
Robie-Suh
K
,
Rieves
D
,
Weiss
K
,
Pazdur
R
:
Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.
Oncology (Williston Park)
2006
;20:1799-1806, 1811; discussion 1811-1713, 1817.
35.
Kontoghiorghes
GJ
.
Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities
.
Expert Opin Drug Saf
.
2007
May
;
6
(
3
):
235
9
.
[PubMed]
1474-0338
36.
Taher
AT
,
Origa
R
,
Perrotta
S
,
Kourakli
A
,
Ruffo
GB
,
Kattamis
A
, et al
New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: results of the randomized, phase II ECLIPSE study
.
Am J Hematol
.
2017
May
;
92
(
5
):
420
8
.
[PubMed]
0361-8609
37.
Vanorden
HE
,
Hagemann
TM
.
Deferasirox—an oral agent for chronic iron overload
.
Ann Pharmacother
.
2006
Jun
;
40
(
6
):
1110
7
.
[PubMed]
1060-0280
38.
Lindsey
WT
,
Olin
BR
.
Deferasirox for transfusion-related iron overload: a clinical review
.
Clin Ther
.
2007
Oct
;
29
(
10
):
2154
66
.
[PubMed]
0149-2918
39.
McLeod
C
,
Fleeman
N
,
Kirkham
J
,
Bagust
A
,
Boland
A
,
Chu
P
,
Dickson
R
,
Dundar
Y
,
Greenhalgh
J
,
Modell
B
,
Olujohungbe
A
,
Telfer
P
,
Walley
T
: Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation. Health Technol Assess
2009
;13:iii-iv, ix-xi, 1-121.
40.
Porter
JB
,
Piga
A
,
Cohen
A
,
Ford
JM
,
Bodner
J
,
Cappellini
MD
.
Assessment of safety in patients receiving longer-term iron chelation therapy with deferasirox who had achieved serum ferritin levels of [{LT}]1000 ng/mL during the study course
.
Haematologica
.
2009
;
•••
:
77
77
.0390-6078
41.
Taher
A
,
El-Beshlawy
A
,
Elalfy
M
,
Zir
KA
,
Daar
S
,
Habr
D
, et al
Deferasirox significantly reduces iron burden in heavily iron-overloaded patients with beta-thalassaemia: 2.7 year Results from the ESCALATOR study
.
Haematologica
.
2009
;
•••
:
82
82
.0390-6078
42.
Schmid
M
,
Cappellini
MD
,
Porter
JB
,
Greenberg
PL
,
Lawniczek
T
,
Glaser
S
, et al
Safety of deferasirox (Exjade®) in myelodysplastic syndromes (MDS) and non-MDS patients with transfusional iron overload : a pooled analysis focusing on renal function
.
Blood
.
2009
.0006-4971
43.
Dell’Orto
VG
,
Bianchetti
MG
,
Brazzola
P
.
Hyperchloraemic metabolic acidosis induced by the iron chelator deferasirox: a case report and review of the literature
.
J Clin Pharm Ther
.
2013
Dec
;
38
(
6
):
526
7
.
[PubMed]
0269-4727
44.
Wei
HY
,
Yang
CP
,
Cheng
CH
,
Lo
FS
.
Fanconi syndrome in a patient with β-thalassemia major after using deferasirox for 27 months
.
Transfusion
.
2011
May
;
51
(
5
):
949
54
.
[PubMed]
0041-1132
45.
Dee
CM
,
Cheuk
DK
,
Ha
SY
,
Chiang
AK
,
Chan
GC
.
Incidence of deferasirox-associated renal tubular dysfunction in children and young adults with beta-thalassaemia
.
Br J Haematol
.
2014
Nov
;
167
(
3
):
434
6
.
[PubMed]
0007-1048
46.
Wong
P
,
Polkinghorne
K
,
Kerr
PG
,
Doery
JC
,
Gillespie
MT
,
Larmour
I
, et al
Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria
.
Bone
.
2016
Apr
;
85
:
55
8
.
[PubMed]
8756-3282
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