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