Transcript Slide 1

Exjade One Year Experience
Dr Khawla Belhoul
Director Thalassemia Center
9Th February 2008
The Aim of This Presentation
Is to present our experience with Exjade (Deferasirox or
ICL670) in the context of
1. Effects on serum Ferritin in chronically transfused
patients who had received Desferoxamine earlier.
2. Side effects and patients tolerance to the drug
3. Effects on Serum Creatinine and liver
Transaminases
4. Improving patients quality of life
5. Other side observations
Exjade One Year Experience
at Thalassemia Center Dubai
 N=135
 > 12 months taking Exjade
 Transfusion-dependent (Thalassemia Major) with ≥
100 ml/kg cumulative prior PRBC
 Prior DFO therapy at an average daily dose of =
40mg/kg/day
 Average starting S. Ferritin =2353mg/dl
 Exjade dose was prescribed according to FDA approved
prescribing information
 Exjade 20 to 30 mg/kg/day for 1 year
 The youngest patient was 4 yr old & the oldest was 38
yr old
Exjade One Year Experience
at Thalassemia Center Dubai
Age Distribution
n=135
>12 yrs
53%
<=12 yrs
47%
Exjade One Year Experience
at Thalassemia Center Dubai
95 Patients (71%) were ≤18 yr
47%
24%
29%
Exjade One Year Experience
at Thalassemia Center Dubai
Exjade One Year Experience
at Thalassemia Center Dubai
Nationality (n=135)
UAE
IN
Oman
Other Arabs
18%
Others
5%
53%
14%
10%
Exjade One Year Experience
at Thalassemia Center Dubai
Baseline Serum Ferritin ≤ 2000mg in 60%
12.5%
27.5%
60%
• Exjade Staring dose was 20mg /kg /day
• Dose increment was slow for the first 4 months
because of frequent initial supply interruptions
• The supply was constant and adequate for the
last 6 months
• Exjade Average Dose in the Last 6 months was
26mg/kg/day
• Max. dose achieved was 32 mg/kg/day
Exjade One Year Experience
at Thalassemia Center Dubai
Average Dose in mg/kg/day
Average Dose (mg/kg/day) in the Last 6 months =26mg/kg
Max. dose = 32 mg/kg/day
NO. of patients
Exjade One Year Experience
at Thalassemia Center Dubai
Overall Ferritin over time
(n=135, mean +/- SD)
6000
Ferritin Level
5000
4000
3000
Low Baseline Ferritin
Medium Baseline Ferritin
High Baseline Ferritin
2000
1000
<=2000
2000 to 4000
>=4000
81
37
17
14
on
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12
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11
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10
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8
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7
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6
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3
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2
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1
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0
Treatment duration
Serum Ferritin remained static at an average Exjade dose of
26mg/kg/day compared to earlier average Desferal dose of 40
mg/kg /day..
Exjade One Year Experience
at Thalassemia Center Dubai
The effect on serum Ferritin was consistent whatever the initial serum Ferritin .
Exjade One Year Experience
at Thalassemia Center Dubai
Absolute change in S. Ferritin
2000.00
Ferritin level
1500.00
1000.00
500.00
0.00
-500.00
<=20
20 to 25
>=25
-1000.00
-1500.00
-2000.00
Average dose overall
The absolute change in serum Ferritin was dose dependent and started
to be negative as we moved toward higher doses.
Exjade One Year Experience
at Thalassemia Center Dubai
Serum Ferritin remained static at an average Exjade dose
of 26mg/kg/day compared to earlier average Desferal
dose of 40 mg/kg /day.
•
•
•
Significant reduction in serum Ferritin in
chronically transfused patients on Exjade
was commonly observed with an average
daily dose equal or above 30mg/kg daily
Serum Ferritin is reliable at low and
normal levels, but loses accuracy as the
iron load rises.
Many factors independent from iron
stores, may significantly alter the serum
Ferritin concentration.
S. Creatinine Normal Values
• It depends on muscle mass.
• A normal value is 0.8-1.3 mg/dL for
men and 0.6 to 1.0 mg/dL for women.
• It is important to take into account
serum creatinine trend rather than
isolated values.
• A Creatinine of 1.0mg/dL might be
normal or might be abnormal if it has
recently increased from 0.6 to 1.0
mg/dL.
Exjade One Year Experience
at Thalassemia Center Dubai
The P value is 0.0011
Creatinine over time
(mean +/- SD)
1.20
Low Baseline Ferritin, n=81
Creatinine Level
1.00
0.80
0.60
0.40
0.20
13
12
11
10
14
m
on
th
m
on
th
m
on
th
m
on
th
8
7
6
9
m
on
th
m
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m
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m
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th
4
3
2
1
5
m
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0.00
Treatment duration
Serum creatinine rise above baseline was observed in almost all the patients
but remained within normal range. The consistency in Serum creatinine rise was
statistically Significant (P value = 0.0011)
Exjade One Year Experience
at Thalassemia Center Dubai
S. Creatinine rise
N=135
Exjade One Year Experience
at Thalassemia Center Dubai
S. Creatinine rise
N=135
Exjade One Year Experience
at Thalassemia Center Dubai
•
•
•
•
•
•
•
•
S. Creatinine rise was frequent.
S. Creatinine rise was often transient.
Serum creatinine rise > 30% at 2 consecutive readings post
baseline was higher among our patients compared to the
internationally released data . But less patients required dose
interruption because of sustained creatinine increase.
Paediatric age group and those with law starting serum Ferritin
appeared to be more liable to creatinine rise.
The Creatinine elevations remained within the normal range
Significant or persistent rise reverted to baseline once treatment
temporarily adjusted or stopped.
None of the patients needed to be excluded from the treatment
because of sustained Creatinine rise.
None Developed renal failure
Exjade One Year Experience
at Thalassemia Center Dubai
17
Reactions in 15 patients had necessiated intrruption or
reduction of the Exjade dose
11%
Exjade One Year Experience
at Thalassemia Center Dubai
n=17
Fever
1
Loss of appetite
1
Significant S-creatinine
rise
9
Palpable pupura
1
Skin rash or urticaria
4
Loose stool
1
0
2
4
6
8
10
Exjade One Year Experience
at Thalassemia Center Dubai
Exjade One Year Experience
at Thalassemia Center Dubai
Action
Treatment was discontinued in
only one patient because of drug
fever
%
0.75%
Treatment was continued in 134
out of 135 patients
99.25%
Exjade One Year Experience
at Thalassemia Center Dubai
Causes of Low Neutrophils ’ Count observed in 5 patients
No.
Hypersplenism
2
Interferon & Rebavirin therapy for Hepatitis C
2
Hydroxyurea, count improved after stopping it
1
Exjade One Year Experience
at Thalassemia Center Dubai
In 30% Who Completed Annual Tests
ENT
Nil
Ophthalmic
Nil
Echo*
Nil
*NO INCREMENT OR DETERIORATION OBSERVED IN EF
Patients’ Satisfaction
Patients’ Satisfaction Questionnaire
Patients’ Satisfaction Questionnaire
Patients’ Satisfaction Questionnaire
Patients’ Satisfaction
I was troubled by nausea and I was finding it difficult
to go to sleep in the beginning but after few weeks I
felt normal and I enjoyed being free from daily
injections.
The taste wasn't terrible but it took 15 MINUTES to
dissolve this stuff!! As much as I'm complaining - it's
still much better than 12 hours/night Desferal.
It doesn’t taste good but taste doesn’t matter, it’s a
hundred times better than poking yourself at night.
Patients’ Compliance
Exjade introduction appeared to have
improved our patients adherence to
medication……….
Adherence to chronic pharmacologic therapy is always
challenging .
Chelation adherence is an important issue in the course
of treatment of patients with Thalassemia major.
The effect of patients’ education and motivation was
thoroughly investigated among patients with many other
chronic disorders, but was never tested among
Thalassemia Major patients..
Method

40 Thalassemia major patients randomly selected, regardless of the
type of iron chelator used.

Age was 10years and above.

These patients were subjected to compliance improvement project.

Improvement in compliance was assessed by observing the effect on
serum Ferritin.
Method
These patients were subjected to intensive education for
6 weeks (2 visits ) in the form of



Self-compliance assessment scale
Compliance assessment scale by doctors, social worker and
nurses
Extensive education
• Health care provider intervention tool
• Group PowerPoint presentation and discussion on iron
overload and iron chelator use.
• Group Round table discussions.
Method

The patients were also called every other week by phone.

The education stopped at 6 weeks and patients Serum Ferritin
trend was observed for the following 10 weeks.
Doctor ,nurse and social
worker intervention tool
Patients’ Compliance
30
27
No. of pts
25
20
15
12
10
5
1
0
Exjade
Desferal
Desferal/Deferipron
Compliance Improvement Project
Follw up of patients on Exjade
4000
3693
3500
3492
3017
3000
2500
Average
2000
S.ferritin
1500
1000
500
0
Baseline/Sep-07
Intensive education
period
Nov-07
Jan-08
Intensive
education stopped
Compliance Improvement Project
follow up of patients on Desferal
3500
3210
3000
2930
2500
Average 2000
S.ferritin 1500
1000
500
0
Baseline/Sep-07
Jan-08
Compliance Improvement Project
Follow up of All Patients
4000
3500
3495
3294
2992
3000
Average 2500
S.ferritin 2000
ng/ml 1500
1000
500
0
Baseline/Sep-07
Intensive education
period
Nov-07
Jan-08
Intensive education
stopped
• Serum Ferritin declined while on intensive
education irrespective of the chelating agent
used.
• Serum Ferritin started to rise again once
intensive education was interrupted irrespective
of the chelating agent used.
• Causes of noncompliance were also studied
among the same group of patients intensively
Causes of Non-compliance to Desferal
Causes for non compliance to Desferal
46.1%
50
40
% of
patients
30.7%
30
20
7.7%
7.7%
7.7%
10
0
Forgetting Inconvenience Difficulty with
self injection
Others
Nil
Causes of Non-Compliance to Exjade
Causes for non compliance to Exjade
% of
patients
45
40
35
30
25
20
15
10
5
0
38.7%
32.2%
16.1%
9.7%
3.2%
Forgetting
Food
Restriction
Nil
Non-Compliance to Iron Chelation
CAUSE
EXJADE
DESFERAL
Forgetting
38.7%
30.7%
Inconvenience
9.7%
46.1%
Nil
32.2%
7.7%
?
Exjade One Year Experience
at Thalassemia Center Dubai
Summary
– Serum Ferritin remained static at an average dose of 25mg/kg/day compared to
earlier average Desferal dose of 40 mg/kg /day
– Exjade Was generally well tolerated
– Mild Creatinine elevations, skin rash and mild gastrointestinal side effects were
the commonest adverse experiences
– Serum creatinine rise > 30% at 2 consecutive readings post baseline was higher
among our patients
– But less patients required dose reduction or interruption because of sustained
creatinine increase
– Paediatric age group and those with law starting serum Ferritin appeared to be
more liable to creatinine rise.
– The Creatinine elevations remained within the normal range
– Side effects appeared to be potentially related to excessive and rapid chelation
– No cases of arthropathy, or agranulocytosis
– No renal failure
– No deaths
Exjade One Year Experience
at Thalassemia Center Dubai
Summary
• Patient adherence to medical therapy has been called
“the next frontier in quality improvement.”
• Exjade introduction appeared to have improved our
patients adherence to medication.
• Without effective patients’ education and motivation,
the benefits of such valuable and expensive drug can
simply be wasted.