infliximab multinational psoriatic arthritis controlled trial (impact)
TRANSCRIPT
Infliximab Multinational Infliximab Multinational Psoriatic Arthritis Controlled Psoriatic Arthritis Controlled
Trial (IMPACT)Trial (IMPACT)
The IMPACT Trial The IMPACT Trial CentersCenters
• Kalden/Antoni Erlangen, Germany
• Burmester/Schneider Berlin, Germany
• Smolen/Ebner Vienna, Austria
• Kirkham London, United Kingdom
• Keystone/Gladman Toronto, Canada
• Kavanaugh/Tutuncu San Diego, California
• Weisman/Wallace Los Angeles, California
• Furst/Molitor Seattle, Washington
• Wassenberg Ratingen, Germany
• Multi-center, randomized, double-blind placebo controlled study in patients with active psoriatic arthritis
• 104 patients at 9 sites in Canada, Europe and USA
Study DesignStudy Design
Study DesignStudy Design
• Dosing: – Placebo vs. Infliximab 5 mg/kg at weeks 0, 2, 6
and 14, open label q 8 week in follow-up
• Endpoints (week 16):– Primary: ACR 20– Secondary: PsARC, PASI, ACR 50, ACR 70,
dactylitis, enthesiopathy, Schober index, DAS
• On-going open-label follow-up through 1 year and a 2 year extension
IMPACT Inclusion CriteriaIMPACT Inclusion Criteria
• > 18 years old
• PsA with peripheral polyarticular involvement for >6 months
• Typical psoriatic arthritis presentation with /without active skin lesions
IMPACT Inclusion CriteriaIMPACT Inclusion Criteria
• Negative for RF
• Active disease (5 joints and ESR>28, or CRP> 15, or morning stiffness > 45 minutes)
• At least 1 DMARD failure
• Stable DMARD dosing > 4 weeks, if applicable
• Stable prednisone <10 mg/day for 2 weeks
• Stable NSAIDS for 2 weeks
IMPACT Exclusion CriteriaIMPACT Exclusion Criteria
• Pregnant, nursing, planning pregnancy in 6 months
• Other confounding conditions/ uncontrolled diseases
• Parenteral corticosteroids within 4 weeks of screening
• Prior treatment with monoclonal antibody
• Chronic infections
• Active TB within 3 years, opportunistic infection within 2 months
• Malignancy within 5 years
Controlled Open-label
Week 0 2 6 14 16* 18 22 30 38 46
Group I P P P P In In In In In In
Group II In In In In P P In In In In
P= Placebo In= Infliximab (5mg/kg)
1:1 randomisation
*At Week 16, group I received an induction regimen of infliximab 5 mg/kg and group II received a placebo induction regiment to maintain blind of original treatment randomization throughout the open label phase
Treatment RegimensTreatment Regimens
Patient PopulationPatient Population
PlaceboInfliximab
Disease duration (years) 8.5 8.7
Skin Involvement (%) 73.1 76.9
Concomitant DMARDs (%) 78.8 63.5
Concomitant MTX (%) 65.4 46.2
Concomitant NSAIDs (%) 78.8 88.5
Concomitant Corticosteroids (%) 28.8 17.3
Mean Baseline ActivityMean Baseline Activity
Placebo Infliximab
Tender Joint Count 20.4 23.7
Swollen Joint Count 12.6 13.0
Physician Global (0-100) 52.4 53.6
Patient Global (0-100) 57.5 51.0
Patient Pain (0-100) 56.0 53.4
HAQ Disability Index (0-3) 1.2 1.2
CRP (mg/L) 31.1 21.7
Efficacy ResultsEfficacy Results
Week 16 Results PsARC Week 16 Results PsARC
18.4
78.0*
0
20
40
60
80
100
Placebo Infliximab
*p<0.0001
Per
cen
t o
f P
atie
nts
Week 50 Results PsARC Week 50 Results PsARC
80.9 81.8
0
20
40
60
80
100
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Week 16 Results Proportion of Week 16 Results Proportion of DAS 28 RespondersDAS 28 Responders
23.1
84.6
0
20
40
60
80
100
Placebo Infliximab
Patients with a Good or Moderate DAS28 Response at Week 16
Per
cen
t o
f P
atie
nts
Week 50 Results Week 50 Results Proportion of DAS 28 RespondersProportion of DAS 28 Responders
76 74
0
20
40
60
80
100
Placebo Infliximab
Patients with a Good or Moderate DAS28 Response at Week 50
Per
cen
t o
f P
atie
nts
Proportion of DAS28 Proportion of DAS28 Responders Over TimeResponders Over Time
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
0
20
40
60
80
100
Placebo Infliximab
Patients with a Good or Moderate DAS28 Response
Week
2 6 14 16 22 30 38 46 50
DAS28 Score Over TimeDAS28 Score Over Time
Mean Values
Mea
n D
AS
28
Sco
re
0
1
2
3
4
5
6
Placebo Infliximab
<3.2 Good Response
>5.1 Non-responders
Week 2 6 14 16 22 30 38 46 500 10 18
DAS28 Score Over TimeDAS28 Score Over Time
0
1
2
3
4
5
6
Placebo Infliximab
Median Values
Week
Med
ian
DA
S 2
8 S
core
<3.2 Good Response
>5.1 Non-responders
2 6 14 16 22 30 38 46 500 10 18
DAS Original Score Over TimeDAS Original Score Over Time
Mean Values
Mea
n D
AS
Sco
re
0
0.5
1
1.5
2
2.5
3
3.5
4
Placebo Infliximab
<2.4 Good Response
>3.7 Non-responders
Week2 6 14 16 22 30 38 46 500 10 18
DAS Original Score Over TimeDAS Original Score Over Time
Median Values
Med
ian
DA
S S
core
0
0.5
1
1.5
2
2.5
3
3.5
4
Placebo Infliximab
<2.4 Good Response
>3.7 Non-responders
Week
2 6 1416 22 30 38 46 500 10 18
Week 16 Results Week 16 Results Proportion of DAS Original RespondersProportion of DAS Original Responders
19.2
76.9
0
20
40
60
80
100
Placebo Infliximab
Patients with a Good or Moderate DAS Response at Week 16
Per
cen
t o
f P
atie
nts
Week 50 Results Week 50 Results Proportion of DAS Original RespondersProportion of DAS Original Responders
71.2 71.2
0
20
40
60
80
100
Placebo Infliximab
Patients with a Good or Moderate DAS Response at Week 50
Per
cen
t o
f P
atie
nts
Proportion of DAS Original Proportion of DAS Original Responders Over TimeResponders Over Time
0
20
40
60
80
100
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Patients with a Good or Moderate DAS Response
Week2 6 1416 22 30 38 46 500 10 18
Week 16 Results: ACR 20, 50, 70Week 16 Results: ACR 20, 50, 70
9.60 0
28.9*
48.0*
67.3*
0
20
40
60
80
100
ACR 20 ACR 50 ACR 70
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
*p<0.0001*p<0.0001
Week 50 Results: ACR 20, 50, 70Week 50 Results: ACR 20, 50, 70
73.1
42.3
32.7
67.3
50.0
34.6
0
20
40
60
80
100
ACR 20 ACR 50 ACR 70
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 20 by ESR SubgroupsACR 20 by ESR Subgroups
70.8 75.066.7 67.7
0
20
40
60
80
100
ESR <28 mm/hour
ESR ≥28 mm/hour
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 50 by ESR SubgroupsACR 50 by ESR Subgroups
41.750.050.0 50.0
0
20
40
60
80
100
ESR <28 mm/hour
ESR ≥28 mm/hour
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 70 by ESR SubgroupsACR 70 by ESR Subgroups
29.235.733.3 35.3
0
20
40
60
80
100
ESR <28 mm/hour
ESR ≥28 mm/hour
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 20 by CRP SubgroupsACR 20 by CRP Subgroups
68.6
82.4
65.672.7
0
20
40
60
80
100
CRP <15 mg/L
CRP ≥15 mg/L
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 50 by CRP SubgroupsACR 50 by CRP Subgroups
42.952.9
46.3
63.6
0
20
40
60
80
100
CRP <15 mg/L
CRP ≥15 mg/L
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week 50 Results: Week 50 Results: ACR 70 by CRP SubgroupsACR 70 by CRP Subgroups
25.7
47.139.0
18.2
0
20
40
60
80
100
CRP <15 mg/L
CRP ≥15 mg/L
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Proportion of Patients Achieving Proportion of Patients Achieving ACR 20 Over TimeACR 20 Over Time
0
20
40
60
80
100
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week2 6 1416 22 30 38 46 500 10 18
Proportion of Patients Achieving Proportion of Patients Achieving ACR 50 Over TimeACR 50 Over Time
0
20
40
60
80
100
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week2 6 14 16 22 30 38 46 500 10
Proportion of Patients Achieving Proportion of Patients Achieving ACR 70 Over TimeACR 70 Over Time
0
20
40
60
80
100
Placebo Infliximab
Per
cen
t o
f P
atie
nts
Res
po
nd
ing
Week
2 6 1416 22 30 38 46 50
Enthesitis Over TimeEnthesitis Over Time
*p=0.05 vs placebo*p=0.05 vs placebo
0
5
10
15
20
Placebo Infliximab
Nu
mb
er o
f P
atie
nts
wit
h
En
thes
itis
**
Week
0 16 50
Enthesitis Over TimeEnthesitis Over Time
13
3
13
7
4
15*
0
5
10
15
20
Baseline Week 16 Week 50
Placebo Infliximab
Nu
mb
er o
f P
atie
nts
wit
h
En
thes
itis
*p=0.05 vs placebo
Dactylitis ScoreDactylitis Score
1.52
1.00
0.36
1.90
0.22 0.22
0.0
1.0
2.0
3.0
Baseline Week 16 Week 50
Placebo Infliximab
Dac
tyli
tis
Sco
re
Dactylitis ScoreDactylitis Score
0.0
0.5
1.0
1.5
2.0
Placebo Infliximab
Dac
tyli
tis
Sco
re
Week
0 16 50
Baseline PASIBaseline PASI
Placebo Infliximab
n = 52 n = 52
Subjects with Any Skin n= 42 n= 42 Involvement
Subjects with PASI >2.5 n = 18 n = 21
Mean Baseline 7.96 (2.7-27.9) 8.88 (2.8-26.1)
Week 16 Results: PASIWeek 16 Results: PASI
Placebo Infliximab
Mean PASI Baseline 7.96 8.88
Mean PASI Week 16 8.71 1.62
% Change of Mean -29.6% 81.5%*
> 75% Improvement 1 subjects 14 subjects (0.05%) (67%)**
Week 50 Results: PASIWeek 50 Results: PASI
Placebo Infliximab
Mean PASI Baseline 7.96 8.88
Mean PASI Week 50 2.48 1.73
% Change of Mean 47.6% 72.1%*
> 75% Improvement 8 subjects 12 subjects (44%) (57%)
ConclusionsConclusions
• Infliximab treatment is effective in PsA– Reduction in synovitis and psoriatic lesions at
Week 16• 81% Mean reduction in PASI in infliximab
group • 67% achieved >75% Improvement in PASI
– Week 50