Transcript Slide 1

At least one mobile phone
will ring during a meeting or
concert
Anything that can go wrong
will go wrong
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 Transaminase
4. Other side observations
450
Total number of patients on Exjade at Thalassemia
Center - Dubai
400
423
350
300
250
200
293
69%
150
100
50
0
On Exjade
TOTAL
Inclusion Criteria
1. Transfusion-dependent Thalassemia patients with ≥
100 ml/kg cumulative prior PRBC.
2. No contraindication to Exjade therapy
3. Prior DFO therapy at an average daily dose of = 4050mg/kg/day
4. Started on Exjade in 2006.
Exjade 2 Years Experience
1. N=135 in 2007 reduced to N=134 in 2008
2. Follow up period: from date of initiation of therapy
in 2006 to Dec.2008(24-28months)
3. Average pre-treatment serum ferritin was calculated
as the average of 3 pretreatment serum ferritin
readings at least 2 months a apart.
4. Other baseline investigations:
Urea,electrolytes,s.creatinine,FBC,transaminases,EC
G,Echocardiography,audiometry,and ophthalmic
evaluation
95 Patients
(71%)
were ≤ 18 year
The youngest patient Was 4-year old &
the Oldest was 38- year old
Age Distribution
n=135
>12 yrs
53%
<=12 yrs
47%
Maximum Prescribed Dose of Exjade
37.5
mg/kg
32
mg/kg
P value is < 0.0001
Serum Ferritin
Month
Dec-08
Nov-08
Oct-08
Sep-08
Aug-08
Jul-08
Jun-08
May-08
Apr-08
2007 N=135
Mar-08
Feb-08
Jan-08
Dec-07
Nov-07
Oct-07
Sep-07
Aug-07
Jul-07
Jun-07
May-07
Apr-07
Mar-07
Feb-07
Jan-07
Mean Ferritin
P value is 0.1781,
2008 N=134
4000
3500
3000
2500
2000
1500
1000
500
0
S. Ferritin (<500ng/ml)
Baseline
S. Ferritin
<500ng/ml
0
End 2007 End
2008
2008
0
19(16%)
low serum Ferritin
50
45
44
(36%)
41
(30%)
37
(27 6%)
40
35
30
25
20
19
(16%)
15
10
<1500 ng/ml
5
<500 ng/ml
0
baseline ferritin
end 2007
end 2008
Factor
# of cases
Age :≤ 12 yr
S. Ferritin (<500ng/ml)
7
Age :>12 yr
11
Males
6
12
Females
Min. age
5
Max. age
33
Mean age(yrs)
14.8
Max. Baseline S.ferritin
9326
732
Min Basline. s.ferritin
Mean Basline s.ferritin
2357
0
Month
Dec-08
70
Nov-08
P value =0.1598,
Oct-08
Sep-08
Aug-08
Jul-08
Jun-08
May-08
Apr-08
Mar-08
Feb-08
Jan-08
Dec-07
Nov-07
Oct-07
Sep-07
Aug-07
Jul-07
Jun-07
May-07
Apr-07
Mar-07
Feb-07
Jan-07
Mean SGOT, 135 patients
<12 yrs
12-18 yrs
>18 yrs
60
50
40
30
20
10
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Month
Dec-08
Nov-08
P value is 0.8309
Oct-08
Sep-08
Aug-08
Jul-08
Jun-08
May-08
Apr-08
Mar-08
Feb-08
Jan-08
Dec-07
Nov-07
Oct-07
Sep-07
Aug-07
Jul-07
Jun-07
May-07
Apr-07
Mar-07
Feb-07
Jan-07
Mean Creat, 135 patients
<12 yrs
12-18 yrs
>18 yrs
Temporary Dose Interruption or Reduction
# CASES
# CASES
2007
low S. Ferritin
(<500mg/dl)
2008
0
19 (70%)
Drug Side effects
15(100%)
7(26%)
Reporting error
0
1(4%)
total
15
27
REASONS
*17 reactions seen in 15 patients
Side Effects that Necessitated Reduction
or Interruption of Treatment
Total=24
Side Effects
17
70%
7
30%
end 2007
end 2008
Side Effects that Necessitated Reduction
or Interruption of Treatment
Total=24
Side Effects
18
16
14
12
10
8
6
4
2
0
end 2007
end 2008
Side Effects that Necessitated
Reduction or Interruption of
Treatment
TOTA L
2007
S.Creatinine rise >50% baseline
13
9
4
5
0
0
2
2
1
1
0
17
7
(70%)
(30%)
2008
(54%)
Allergic Skin Reactions
5
(21%)
Transaminase Rise > 5x baseline
2
(8%)
GI. Symptoms
3
(13%)
Fever+/-abdominal pain
1
(4%)
TOTAL
24
Side Effects that Necessitated Reduction or Interruption of Treatment
Fever+/-abd.pain
GI Symptoms
transaminase rise
End 2007
skin reaction
s.creatinine rise
Название оси
CONTINUED
EXJADE
DISCONTINUED
EXJADE
2007
2008
134
(99.3%)
1
(0.7%)
121
(90.3%)
13
(9.7%)
Discontinued Exjade
Exjade side effects
Not side effects related
23%
3
77%
10
DISCONTINUED EXJADE
2008
CAUSES
# CASES
low MRIT2*
4
3
2
1
1
1
1
13 (9.7%)
On patients' request
None Exjade related death
Heart failure (MRIT2*=7)
Fever +/_Abd.pain
Renal impairment
Severe GI symptoms
TOTAL
OTHER SCREENING TESTS
During 2008
Result
Ophthalmology
Same as baseline
Audiogram
Same as baseline
Echo/EF
No significant change
Other Observations
1. Our nursing staff observed that patients pre-transfusion HB.
is rising after starting Exjade. To validate this observation:
2. Baseline pre-transfusion HB. was calculated as = average of 6
visits readings before starting Exjade in 2006.
3. End of 2008 pre-transfusion HB. was calculated as = average
of 6 last visits readings in 2008.
4. Mean and average of the too groups was compared.
Mean pre-transfusion HB; baseline versus end 2008
Mean baseline
pre-transfusion HB versus end of 2008
P value is 0.1949
9,46
9,44
9,42
9,4
9,38
9,36
9,34
Pre- transfusion
HB.BEFORE
baseline
Pre- transfusion
HB. End 2008
AFTER
1-Possible Interference -> introduction of leukodepleted PRC In
July 2008.
2-A case- control using Desferal is needed .
CONCLUSION
-Exjade appeared to be safe over the last 2 years with
limited and usually reversible side effects.
-Using serum S.Ferritin as a guide; Exjade appeared to be
as effective as Desferal.
-We hope to be able to correlate our result to MRIT2* at
the end of 2009.
-We need to study in depth the characteristics of the
responders to Exjade.
AKNOWLEDGMENT
oDr Ahmed M.A. Khadem
oMiss Meitha M.Hassan
oMrs Maria A.J.Pinto
oMiss Maryam Omar Ali
THANK YOU