PowerPointPrsentation

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FK 506 MONOTHERAPY AFTER EARLY STEROID REDUCTION
FOR LIVER TRANSPLANT RECIPIENTS A PROSPECTIVE
RANDOMIZED, DOUBLE BLINDED, PLACEBO CONTROLLED
TRIAL Christian Moench, Alexander Grebe, Markus
Schuchmann and Gerd Otto Department of
Transplantation Surgery / I Department of
Medicine Johannes Gutenberg University, MAINZ,
GERMANY
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Immunosuppression
FK 506 Basic immunosuppression 10-15 ng/ml
during the first 6 weeks 5-10ng/ml after 6
weeks Steroids Methylprednisolon during the first
14 days in both goups After Day 14 Steroid
group Methylprednisolon until month
6 Placebo group Placebo until month 6 No other
immunosuppressive agents !
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Steroids during the first 14 days
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Immunosuppression
Steroid group
FK 506 and - 12mg Methylprednisolon until month
2 - 8mg Methylprednisolon until month 6
FK 506 and steroids
Placebo group
FK 506 and - Placebo until month 6
OLT
d 14
month 6
month 12
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Inclusion / exclusion criteria
Inclusion-criteria - recipients of a primary
liver graft - age 18 years Exclusion-criteria
- liver re-transplantation - steroid treatment 6
months before OLT - pregnancy - other
immunosuppresive drugs besides the trial - HIV
infection - FK 506 hypersensitivity
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Study endpoints
Primary endpoints - post transplant diabetes -
hypercholesterolaemia / hypertriglyceridaemia -
hypertension - infection rate Secondary
endpoints - acute / chronic rejection -
patient- and graft survival
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Acute rejection

• - all rejections had to be biopsy prooven
• treatment with pulsatile bolus steroids (500mg
  methylprednisolone i.v. over 3 days)
• - patients with more than 2 rejections or
  steroidresistant rejection were removed from the
  trial and went on individual immunosuppression
  (MMF / Steroids)

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Demographics 02/00 until 07/04
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Patient survival p0.5726
Steroid group 88.8
Placebo group 85.7
days
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Reasons for Death
Sepsis 5 (2 Placebo) Tumor 4 (3
Placebo) HCV Reinfection 2 (1
Placebo) Renal failure 1 Pulmonary
failure 1 (1 Placebo) Non compliance 1
n 14 (50 Placebo)
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Not finished follow up
FK 506 side effects 13 (5 Placebo) Death
14 (7 Placebo) Recurrent rejection 10 (5
Placebo) Re-transplantation 1 (1
Placebo) Permission refused 1
n 39 (46 Placebo)
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Side effects under FK 506 therapy
Neurological 7 (4 Placebo) Renal failure 3
(1 Placebo) Diarrhea 2 Haemolysis 1
n 13
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Acute rejection rate

100
p0.443
90
80
70
60
50
40
n27 48.2
30
n19 35.2
20
10
0
Steroid group Placebo group
RAI 4.72 /- 1.45 4.20 /- 1.61
p0.792
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Recurrent acute rejection rate
100
Recurrent p0.738 rejection
90
80
70
Single episode p0.513
60
50
40
30
n20 35.7
20
n14 25.9
n7 12.5
n5 9.3
10
0

Steroid group Placebo group
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Chronic rejection
- n2 (out of 56) in Placebo group
(3.6) after 78 days and 247 days - primary
diagnosis Wilsonss disease Alcoholtoxic
cirrhosis - n0 (out of 54) in Steroid group
(0) - p0.496
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Cumulative rejection rate p0.1968
Placebo group 48
Steroid group 35
days
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CMV infection rate

100
p0.403
80
60
40
n18 33.3
n14 25.0
20
0
Steroid group Placebo group
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Fasting glucose levels
Baseline p0.985
6 Months p0.225
12 Months p0.919
mg/dl
p0.001
200
p0.365
180
160
140
120
100
80
60
40
p0.019
20
0
p0.277
Steroid group
Placebo group
19
Post transplant diabetes
20
Hypertension
21
Cholesterol levels
Baseline p0.046
6 Months p0.468
12 Months p0.022
mg/dl
p0.008
300
p0.080
200
100
p0.670
p0.013
0
p0.004
Steroid group
Placebo group
22
Hypercholesterolaemia
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Triglyceride levels
Baseline p0.473
6 Months p0.366
12 Months p0.978
mg/dl
400
p0.425
300
p0.0001
200
100
0
p0.009
p0.232
Steroid group
Placebo group
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Hypertrigylceridaemia
25
HCV
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Conclusion

• Early steroid withdrawl under FK 506 is feasible
  and safe after OLT
• No significant difference in acute and chronic
  rejection rates
• Significant lower rates of post transplant
  diabetes and hypercholesterolaemia
  /hypertriglyceridaemia without steroids
• Lower rate of CMV infection without steroids (n.
  s.)
• No impact on Hypertension