4/3/2018

1

Psoriasis: Which Drug for Which Patient?

Mark Lebwohl, MD

Sol and Clara Kest ProfessorAnd Chairman

Kimberly and Eric J. Waldman Department of Dermatology

Icahn School of Medicine at Mount Sinai

DRUG PsA

ETANERCEPT

ADALIMUMAB

INFLIXIMAB

CERTOLIZUMAB

GOLIMUMAB

USTEKINUMAB

SECUKINUMAB

IXEKIZUMAB

BRODALUMAB

GUSELKUMAB

TILDRAKIZUMAB

RISANKIZUMAB

MIRIKIZUMAB

APREMILAST

METHOTREXATE

CYCLOSPORINE

ACITRETIN

Etanercept in the treatment of

psoriatic arthritis and psoriasis: a

randomised trial.

Mease PJ, et al.

Lancet. 2000;356(9227):385-90.

Etanercept

ACR Response at 3 Months

ACR 70

Placebo Etanercept

0%

13%

ACR 50

Placebo Etanercept

3%

50%*

0

20

40

60

80

100

ACR 20

% P

ati

en

ts

Placebo Etanercept

13%

73%*

*P<.001

Mease PJ, et al. Lancet 2000;356:385-390.

Biannual radiographic assessments of hands and feetin a three-year prospective followup of patients with early rheumatoid arthritis.

van der Heijde DM, et al Arthritis Rheum. 1992 Jan;35(1):26-34.

Sharp score or van der Heijde

score measures joint damage

on x-ray: narrowing and erosions Mean Change in Erosion Score at 12 Months

Etanercept Inhibited Bone Erosion

p < 0.0001*

Ch

an

ge f

rom

Baselin

e

Placebo (n=104)

Etanercept (n=101)

*stratified rank test

0.66

-0.09

-0.5

0.0

0.5

1.0

1.5

Ory P. Arthritis Rheum 2002;46(suppl):S196. Oral presentation 442.

4/3/2018

2

Ch

an

ge f

rom

Baselin

e

p = 0.044*

Mean Change in JSN Score at 12 Months

Etanercept Inhibited Joint Space Narrowing

*stratified rank test

Placebo (n=104)

Etanercept (n=101)

0.34

0.05

-0.5

0.0

0.5

1.0

1.5

Ory P. Arthritis Rheum 2002;46(suppl):S196. Oral presentation 442.

*stratified rank test

p = 0.0001*

Ch

an

ge f

rom

Baselin

e

Etanercept Inhibited Structural Damage

1.00

-0.03

-0.5

0.0

0.5

1.0

1.5Placebo (n=104)

Etanercept (n=101)

Primary Radiographic Endpoint

Mean Change in Total Sharp Score at 12 Months

Ory P. Arthritis Rheum 2002;46(suppl):S196. Oral presentation 442.

Adalimumab Effectiveness in Psoriatic

Arthritis Trial Study Group. Adalimumab for

the treatment of patients with moderately to

severely active psoriatic arthritis: results of a

double-blind, randomized, placebo-controlled

trial.

Mease PJ, et al.

Arthritis Rheum. 2005;52(10):3279-89.

Adalimumab

Percent ACR Response at Weeks 12 and 24

All results p<0.001 placebo vs adalimumab

14

58

15

57

4

36

6

39

1

20

1

23

0

10

20

30

40

50

60

Placebo Adalimumab Placebo Adalimumab

ACR20

ACR50

ACR70

Perc

en

t o

f P

ati

en

ts

Week 12 Week 24

n=162 n=162n=151 n=151

Mease P, et al. Presented at the 68th Annual Scientific Meeting of the American College of Rheumatology,

October 19, 2004; San Antonio, Texas.

Mean Change in mTSS at Week 24

00

1.0

-0.2

-0.5

0

0.5

1

1.5

Ch

an

ge in

mT

SS

Placebo Adalimumab

Weeks

12 24

N Baseline Mean change

Placebo 152 20.0 1.0

Adalimumab 144 22.3 – 0.2***

***p≤0.001 vs placebo for ranked ANCOVASource: Mease, et al. Presented at: EULAR Congress; June 8-11 2005; Vienna, Austria.

The Infliximab Multinational

Psoriatic Arthritis Controlled Trial

(IMPACT): results of radiographic

analyses after 1 year.

Kavanaugh A, et al.

Ann Rheum Dis. 2006;65(8):1038-43.

4/3/2018

3

InfliximabACR 20 at Week 14 and Week 24

16%11%

54%58%

0

20

40

60

80

100

Week 14 Week 24

Placebo Infliximab

Pro

po

rtio

n o

f S

ub

jects

Ach

ievin

g A

CR

20

p < 0.001* p < 0.001

*Remains significant after multiple sensitivity analyses

Primary Endpoint

Major Secondary Endpoint

European League Against Rheumatism 2004; Oral Presentation: OP0182.

Total vdH-S Score – Mean Change from Baseline at Week 24*

*Median Change in

both groups was 0.0

-1.0

-0.5

0.0

0.5

1.0

Placebo (n=100) Infliximab 5 mg/kg (n=100)

To

tal vd

H-S

Sco

re

p<0.001

-0.70

0.82

Van der Heijde D, et al. Ann Rheum Dis. 2005;64 (Supplement III):109.

Effect of certolizumab pegol on signs

and symptoms in patients with

psoriatic arthritis: 24-week results of a

Phase 3 double-blind randomised

placebo-controlled study (RAPID-PsA)

Mease PJ, Fleischmann R, Deodhar AA,

Wollenhaupt J, Khraishi M, Kielar D,

Woltering F, Stach C, Hoepken B, Arledge

T, van der Heijde D.

Ann Rheum Dis. 2014;73:48-55.

Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody,

inhibits radiographic progression in patients with active

psoriatic arthritis: results of an integrated analysis of

radiographic data from the phase 3, multicentre, randomised,

double-blind, placebo-controlled PSUMMIT-1 and

PSUMMIT-2 trials.

Kavanaugh A, Ritchlin C, Rahman P, Puig L, Gottlieb AB, Li S,

Wang Y, Noonan L, Brodmerkel C, Song M, Mendelsohn AM,

McInnes IB; PSUMMIT-1 and 2 Study Groups.

Ann Rheum Dis.2014;73:1000-6.

4/3/2018

4

ACR20/50/70 Responders at Week 24

19

Kavanaugh A, et al. ACR2012. Abstract 2562.

**p<0.001

*

**

* *

Primary Endpoint

PSUMMIT 1

Ustekinumab

FUTURE 2ACR20 Response Through Week 52

ACR20=American College of Rheumatology 20% improvement; SC=subcutaneous; TNFi=tumor necrosis factor inhibitor.*P<0.0001; †P<0.001; §P<0.01; ‡P<0.05 vs placebo. Missing values were imputed as nonresponse (nonresponder imputation) through Week 52.Kavanaugh A, et al. Presented at American College of Rheumatology Annual Meeting; Nov 6–11, 2015; San Francisco, CA; Oral 2146.

TNFi-Naive

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Re

sp

on

de

rs, %

Weeks

63.5%

36.9%

68.7%

15.9%

58.2%

79.4%

58.5%*

§

§

*

§

*

*

*

*

*

*

*

*

0

10

20

30

40

50

60

70

80

90

100

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Weeks

29.7%

14.3%

14.7%

45.5%

§

‡

§§

§‡

‡

§

*

§

TNFi-Exposed

Secukinumab 75 mg SC

(n=65)

Secukinumab 150

mg SC (n=63)

Placebo

(n=63)

Secukinumab 300 mg SC

(n=67)

Secukinumab 75 mg SC

(n=34)

Secukinumab 150 mg

SC (n=37)

Placebo

(n=35)

Secukinumab 300 mg SC

(n=33)

Re

sp

on

de

rs, %

‡‡

†

37.8%

35.3%

54.5%

‡‡

†

†

Secukinumab

FUTURE 2ACR50 and ACR70 Response Through Week 52

ACR50/70=American College of Rheumatology 50%/70% improvement; SC=subcutaneous; TNFi=tumor necrosis factor inhibitor.

*P<0.0001; †P<0.001; §P<0.01; ‡P<0.05 vs placebo. Missing values were imputed as nonresponse (nonresponder imputation) at Weeks 24

and 52.Kavanaugh A, et al. Presented at American College of Rheumatology Annual Meeting; Nov 6–11, 2015; San Francisco, CA; Oral 2146.

38.8

52.2

44.449.2

24.6

36.9

6.3

0

10

20

30

40

50

60

Week 24 Week 52

Re

sp

on

de

rs, % *

*§

27.3 27.3

18.921.6

5.9

17.6

8.6

0

10

20

30

40

50

60

Week 24 Week 52

Re

sp

on

de

rs, %

‡

TNFi-Naive TNFi-Exposed

n=63n=67 n=65 n=63 n=67 n=63 n=65 n=33 n=37 n=34 n=35 n=33 n=37 n=34

AC

R5

0A

CR

70

*

22.4

26.927.023.8

6.2

20.0

1.6

0

10

20

30

40

Week 24 Week 52

Re

sp

on

de

rs, %

†*

15.218.2

10.813.5

5.98.8

0

0

10

20

30

40

Week 24 Week 52

Re

sp

on

de

rs, %

‡

TNFi-NaiveTNFi-Exposed

n=63n=67 n=65 n=63 n=67 n=63 n=65 n=33 n=37 n=34 n=35 n=33 n=37 n=34

Secukinumab 75 mg SCSecukinumab 150 mg SC PlaceboSecukinumab 300 mg SC

Secukinumab

FUTURE 1: Radiographic progression in PsA patients stratified by MTX use

Gottlieb AB, et al. EADV 2015, P0348 Sponsored by Novartis Pharma AG

0.080.04 0.13

0.57 0.57 0.58

0

0.2

0.4

0.6

0.8

1

Overallpopulation

MTX: Yes MTX: No

Me

an

ch

an

ge

in v

dH

-mT

SS

Pooled SKB doses PBO

Baseline to Week 24 (full analysis set)

0.21

0.29

0.1

-0.03

-0.18

0.25

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

Overallpopulation

MTX: Yes MTX: NoM

ea

n c

ha

ng

e in

vd

H-m

TS

S

Pooled SKB doses PBO switched to SKB

Week 24 to Week 52 (X-ray completers)

366 179216

114 150 65 344 152 206

98

138 54

*P<0.05 vs PBO

Change in mTSS >0.5 considered progression of radiographic disease

* *

Ixekizumab, an interleukin-17A specific

monoclonal antibody, for the treatment of

biologic-naive patients with active psoriatic

arthritis: results from the 24-week randomised,

double-blind, placebo-controlled and active

(adalimumab)-controlled period of the phase

III trial SPIRIT-P1.

Mease PJ, et al

Ann Rheum Dis. 2017;76:79-87.

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active

(adalimumab)-controlled period of the phase III trial SPIRIT-P1. Mease PJ, et al; Ann Rheum Dis. 2017;76:79-87.

4/3/2018

5

Brodalumab Phase 2 PsA study: Clinical response and improvement in psoriasis in subjects with PsA

Mease P, et al. AAD 2014, P7605

ACR20 response rate at Week 24

PBO (n=55) BRO 140 mg q2w (n=57) BRO 280 mg q2w (n=56)

Indicates time point at which all subjects began receiving BRO 280 mg q2w

80

20

0

Pa

tie

nts

(%

±S

E)

2Week

60

40

4 8 12 16 24

43.5

51.1

64.4

*

*

*

*†

†

ACR20Open label

2Week

4 8 12 16 24

19.6

32.7

33.3

*

*

ACR50Open label

Pa

tie

nts

(%

±S

E)

Number of subjects

PBO 54 52 51 52 49 46

140 mg 56 56 51 53 51 47

280 mg 50 55 53 50 49 45

Number of subjects

PBO 54 53 51 52 50 46

140 mg 56 56 53 53 51 49

280 mg 50 55 53 51 50 45

80

20

0

60

40

1. Mease P, et al. Arthritis Rheum 2005;52:3279–89; 2. Mease P, et al. Arthritis Rheum 2004;50:2264–72

3. Antoni C, et al. Ann Rheum Dis 2005;64:1150–7; 4. Kavanaugh A, et al. Arthritis Rheum 2009;60:976–86

5. Mease P, et al. AAD 2014, P7605

5750

54 52

64.4

39 3741

2933.3

23

9

27

18

0

20

40

60

80

100

ADA ETN IFX GLM BRO

Patients

(%

)

Week 24

ACR20 ACR50 ACR70

1 2 3 4

Therapeutic response of PsA to TNFi and brodalumab

5

• No head-to-head trials

• BRO trial is Phase 2, not placebo controlled

• Others are Phase 3 and placebo controlled

N/A

N/A = not available

Figure 2. ACR 20/50/70 Responses at Week 24

18.4

10.2

2.0

58.0

34.0

14.0

0

20

40

60

80

100

ACR20 ACR50 ACR70

% o

f P

ati

en

ts

Placebo (n=49) Guselkumab (n=100)

p<0.001

p=0.023 (post hoc)p=0.002

Primary Endpoint

RESULTS

Gottlieb A, et al. AAD 2017. P4454.

0 0.0

22.4

12.216.3

22.418.4

0

21.0

42.0

49.0

60.063.0

58.0

0

20

40

60

80

100

0 4 8 12 16 20 24

% o

f P

ati

en

ts

Weeks

Placebo (n=49) Guselkumab (n=100)

Figure 3. ACR20 Responses Over Time through Week 24

p<0.001

p=0.019p<0.001

p<0.001 p<0.001p<0.001

Primary Endpoint

RESULTS

Gottlieb A, et al. AAD 2017. P4454.

Apremilast, an oral phosphodiesterase 4 inhibitor,

in patients with psoriatic arthritis and current skin

involvement: a phase III, randomised, controlled trial

(PALACE 3).

Edwards CJ, Blanco FJ, Crowley J, Birbara CA,

Jaworski J, Aelion J, Stevens RM, Vessey A, Zhan

X, Bird P.

Ann Rheum Dis. 2016;75:1065-73.

Longterm methotrexate therapy in psoriatic

arthritis: clinical and radiological outcome.

• Abu-Shakra M, et al.

• J Rheumatol 1995 Feb;

• 22(2):241-5.

• Mtx does not prevent joint damage on x-ray.

4/3/2018

6

CHAMPION: Effect of BMI on the efficacy of adalimumab

• Weight response analysis of

Comparative study of Humiravs Methotrexate vs Placebo In

Psoriasis Patients

(CHAMPION) trial

• Broken down into 3 groups:

– Normal: BMI <25 kg/m2

– Overweight: BMI 25−30 kg/m2

– Obese: BMI >30 kg/m2

• Body weight correlated to

lower levels of response in

CHAMPION, including in

placebo group

Prussick RB, et al. AAD 2015, P1350 Sponsored by AbbVie

PASI 75 and PASI 90 response in patients, stratified by

normal weight, overweight, or obese at baseline

*P<0.05 vs MTX, †P<0.05 vs placebo using Fisher exact test

Placebo

Methotrexate

Adalimumab

Week 12 Week 16

*† *†

*†

*† *†

*†

*†

*†

*†

*

*†*†

15.3%

18.3%

25.4%

31.3%

30.2%

33.0%

32.2%

29.7%

27.0%

17.0%

27.1%

20.7%

14.3%

9.4%

28.6%

40.6%

0% 20% 40% 60% 80% 100%

Superior

Persistently good

Good

Suboptimal

% of patients

Relationship to BMI: Response to 48 wks etanercept 50 mg BIW

Etanercept Response by BMI

50 mg BIW over 48 Weeks

Normal

(BMI<25)

n=106

Overweight

(BMI 25-29)

n=189

Strober et al. Winter AAD, 2006. Poster 2890.

Obese

(BMI 30-39)

n=246

Extremely

obese

(BMI>40)

n=59

Etanercept PASI 75 response at 12 weeks by dose and weight

n=195 n=162 n=218 n=197n=193 n=221

Placebo Etanercept Etanercept

-

25 mg BIW50 mg BIW

Gordon et al. J Am Acad. Derm. 2006;54:S101

Etanercept PASI 75 response in patients >200 lbs

55

41

3

43

3

25

0

10

20

30

40

50

60

% o

f p

ati

en

ts a

ch

iev

ing

PA

SI

75

Patients less than ~200 lbs (<89.4 kg) Patients ~200 lbs and above (>89.4 kg)

Etanercept: PASI-75 at 12 weeks by weight quartiles

42 3 3

31

22

6 7

44

38

30

20

63

47

51

34

0

10

20

30

40

50

60

70

<76.20 kg 76.2 kg ≤ x <89.36 kg 89.36 kg ≤ x < 103.80 kg x ≥103.80 kg

Patient weight groups

Perc

en

tag

e o

f p

ati

en

ts a

ch

ievin

g P

AS

I-75

Placebo (N = 414)

mg QW (N = 160) 25

mg BIW (N = 415) 25

mg BIW (N = 358) 50

*

*

*

*

*

**

***

**

* P < 0.0001 compared with placebo

** P < 0.001 compared with placebo

Pooled analysis of studies 200221632, 20021639, and 20021642

-20

0

20

40

60

80

100

< 50 ≥ 50; <60 ≥ 60; < 70 ≥ 70; < 80 ≥ 80; < 90 ≥ 90; < 100 ≥ 100; <

110

≥ 110; <

120

≥ 120; <

130

≥130; <

140

≥ 140; <

150

≥ 150

Patient weight groups (kg)

Pe

rce

nta

ge

of

pa

tie

nts

ac

hie

vin

g P

AS

I-7

5

Placebo (N = 414)

= mg QW (N 25

)160= mg BIW (N 25

)415= mg BIW (N 50

)358Linear (50 mg

)BIW (N = 358)Linear (25 mg

)BIW (N = 415)Linear (25 mg QW

)(N = 160)

P-values are not available for subgroup analyses of weight in 10 kg increments

Pooled analysis of studies 200221632, 20021639, and 20021642

Etanercept: PASI-75 at 12 weeks by 10 kg increments

63

4546.2

31.6

22.816.7

0

20

40

60

80

100

<90kg ≥90kg

31.2

17.216.39.3

5.61.9

0

20

40

60

80

100

<90kg ≥90kg

82.7

72.773.5

61.4

46.5

38.9

0

20

40

60

80

100

<90kg ≥90kg

SKB 300 mg SKB 150 mg Etanercept

Nonresponder imputation at Week 12 from studies A2302 & A2303

PASI 90 PASI 100

PASI 75

Etanercept vsSecukinumab

4/3/2018

7

UNCOVER-2: Efficacy and safety of ixekizumab stratified by body weight in patients with psoriasis

PASI 90

Puig et al. EADV 2016, FC04.03; Sponsored by Eli Lilly and Company

• IXE q2w is more effective than IXE q4w in heavier patients at Week 12

• Significant drop off of ETN efficacy with weight

• Longer-term analysis would be helpful for determining best dosing for patients ≥80 kg

• Is there a role for continued q2w dosing in some heavier patients?

Re

sp

on

se

s ra

te (%

)

PBO (n=50)

IXE q4w (n=97)

<80 kg ≥80 to <100 kg ≥100 kg

ETN (n=111)

IXE q2w (n=123)

20

60

02 4 8

40

80

100

12Week

0

20

60

02 4 8

40

80

100

12Week

0

PBO (n=61)

IXE q4w (n=130)

ETN (n=121)

IXE q2w (n=133)

20

60

02 4 8

40

80

100

12Week

0

PBO (n=55)

IXE q4w (n=119)

ETN (n=125)

IXE q2w (n=95)

63

4546.2

31.6

22.816.7

0

20

40

60

80

100

<90kg ≥90kg

31.2

17.216.39.3

5.61.9

0

20

40

60

80

100

<90kg ≥90kg

82.7

72.773.5

61.4

46.5

38.9

0

20

40

60

80

100

<90kg ≥90kg

67.7

56.954.5

45.6

30.7

20.4

0

20

40

60

80

100

<90kg ≥90kg

SKB 300 mg SKB 150 mg Etanercept

Nonresponder imputation at Week 12 from studies A2302 & A2303

IGA mod 2011 0/1

PASI 90

PASI 75

PASI 100

Etanercept vs Secukinumab

Skin Clearance Response Rates improve over time on treatment with Brodalumab 210 mg

Q2W in Non-obese and Obese Patients

39

90.4 91.1

75.981.6

0

10

20

30

40

50

60

70

80

90

100

Week 12 Week 52

PASI 75

80.784.4

59.3

71.1

0

10

20

30

40

50

60

70

80

90

100

Week 12 Week 52

PASI 90

55.3

80.0

27.8

52.6

0

10

20

30

40

50

60

70

80

90

100

Week 12 Week 52

PASI 100

Nonobese Obese

• Rates of achieving sPGA 0/1, PASI 75, PASI 90, and PASI 100 were higher among nonobese patients than obese patients at weeks 12 and 52

• The percentage of patients achieving PASI 100 increased from week 12 to week 52 in both nonobese and obese patients

• The safety associated with brodalumab 210 mg Q2W was comparable between nonobese and obese patients (data not shown)

AMAGINE-1Nonobese and obese patients who received continuous brodalumab

210 mg Q2W52 weeks PASI, TEAEs

PASI 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; Q2W, every 2 weeks; sPGA, static physicians global assessment; TEAE, treatment-emergent

adverse event.

Data on File, Valeant Pharmaceuticals North America LLC.

Nonresponder imputation was used to impute missing data.

(Week 12, n=114)

(Week 52, n=45)

(Week 12, n=108)

(Week 52, n=38)

86.8 86.7

63.9

78.9

0

10

20

30

40

50

60

70

80

90

100

Week 12 Week 52

Re

sp

ond

ers

, %

sPGA 0/1

-100 -80 -60 -40 -20 0 20 40 60 80 100

240 85.8249 62.2

349 82.5170 65.9

89 79.885 60.0

147 85.778 62.8

262 84.7277 59.6

408 84.6200 66.0

6 83.38 75.0

6 50.05 60.0

51 80.447 70.2

72 81.937 62.2

182

139

174

25863.3

62.6

87.2

86.8

136

98

137

21566.3

62.5

79.1

81.8

N %N %GuselkumabAdalimumabDiff and 95% CI

Guselkumab vs Adalimumab

Proportion of Subjects Achieving IGA Score of Cleared (0) or Minimal (1) at W eek 24

Voyage 1

Voyage 2

Male

Male

Female

Female

White

White

Black or African American

Black or African American

Asian

Asian

<45 years

<45 years

³45 to <65 years

³45 to <65 years

Sex

Baseline Age

Race

Baseline Demographics

16

11

18

2372.7

43.8

82.6

77.8

191 18972.3 84.7

153 27772.5 87.7

142 14047.9 83.6

94 21953.2 78.1

AdalimumabBetter

GuselkumabBetter

³65 years

³65 years

£90 kg

£90 kg

>90 kg

>90 kg

Baseline Weight

Differences in response arelarger in heavier patients

due to lower response rates in the adalimumab group.

40

VOYAGE 1,2RESULTS

Figure 5. At Week 24, guselkumab therapy was superior to adalimumab across subgroups of patients defined by baseline demographics: IGA 0 or 1

Blauvelt A, et al. AAD 2017. P4895.

Scott E, et al. EADV 2017, P1722 Sponsored by Merck & Co., Inc.

• Pooled analysis from 3 RCTs: reSURFACE 1 and 2 and P05495

• 1⁰ endpoints: • reSURFACE 1/2, PASI 75 and PGA

0/1 at Week 16

• Study P05495, PASI 75 at Week 16

• Randomized patients stratified by body weight (≤90 kg, >90 mg; ≤100 kg, >100 mg

• Authors concluded that PASI and PGA responses were numerically greater in patients with lower vs higher body weight

Impact of body weight on efficacy of tildrakizumab at 12 weeks in moderate to severe chronic plaque psoriasis

TIL 200 mg vs PBO TIL 100 mg vs PBOTIL 200 mg vs ETN TIL 100 mg vs ETN

200

Resp

on

se

rate

(%

)

≤90 kg

4060

10080

PASI 75

Body weight

>90 kg≤100 kg>100 kg

200 ≤90 kg

4060

10080

PASI 90

>90 kg ≤100 kg>100 kg

200 ≤90 kg

4060

10080

PASI 100

>90 kg ≤100 kg>100 kg

200 ≤90 kg

4060

10080

PGA 0/1

>90 kg ≤100 kg>100 kg

4/3/2018

8

PASI-75 Response at Week 16 by Demographic Subgroups – ESTEEM 1 and 2

ESTEEM 1 and 2 (Pooled)

*Adjusted difference in PASI-75 response rate (apremilast 30 mg BID vs. placebo).

Full analysis set using last observation carried forward. Pooled N=1,255.

CI=confidence interval. ESTEEM 1 & 2

*

ESTEEM 1 & 2/PALACE 1–3: Long-term pooled safety of apremilast(≥156 weeks): Body weight assessments

Crowley J, et al. EADV 2016, P2052; Sponsored by Celgene Corporation

Assessment APR-exposure period

0 to ≤52 wks

n=1844

>52 to ≤104 wks

n=1161

>104 to ≤156 wks

n=831

Cumulative eventsa

0 to ≥156 wksn=1844

Baseline weight, mean, kg 89.54 (21.54) 89.50 (21.61) 87.96 (20.28) 89.54 (21.54)

Mean (SD) change from baseline

in weight, kg

−1.42 (4.85) −1.64 (5.82) −1.63 (6.21) −1.34 (6.01)

Mean (SD) % change from

baseline in weight

−1.48 (5.38) −1.70 (6.17) −1.63 (6.72) −1.32 (6.64)

Patients with >5% weight loss,

n/mb (%)

312/1843 (16.9) 284/1160 (24.5) 212/831 (25.5) 388/1843 (21.1)

APR-exposure periods include all patients who received APR regardless of when APR exposure startedaCumulative APR exposure is based on each patient’s total exposure to APR through February 2015bn/m, number of patients with ≥1 occurrence at any time point/number of patients with ≥1 post-baseline value

• With longer-term exposure to APR, safety profile remains stable and favourable

• GI side-effects seem relatively persistent

• Unclear significance of decrease in lymphocyte counts

• Weight loss seems to be common in this population

169 liver bx’s in 71 psoriasis pts on MTX

• Hepatic fibrosis: 71%

• In pts with risk fx: 96%

obesity 14/15

diabetes 7/7

ETOH 9/9

• ↑LFT’s not associated with fibrosis

Rosenberg P, et alJ. Hepatol. 2007;46:1111-8.

The effect of weight reduction on treatment outcomes

in obese patients with psoriasis on biologic therapy: a

randomized controlled prospective trial.

Al-Mutairi N, Nour T.

Expert Opin Biol Ther. 2014;14:749-56.

• TNF blocker x 24w; diet vs control

• PASI 75 was achieved by 85.9% in the diet group, and

59.3% in the control group (p < 0.001)

• w 24: mean ↓ wt = 12.9 ± 1.2 kg w diet

-1.5 ± 0.5 kg control

Early increase of abdominal adiposity in patients with

spondyloarthritis receiving anti-tumor necrosis factor-α

treatment.

Hmamouchi I, Roux C, Paternotte S, Kolta S,

Dougados M, Briot K.

J Rheumatol. 2014;41:1112-7.

CONCLUSIONS

• In obese patients higher doses or

stronger medications are more effective

• Weight loss helps

4/3/2018

9

Risk of myocardial infarction in

patients with psoriasis. Gelfand JM, Neimann AL, Shin DB,

Wang X, Margolis DJ, Troxel AB.

JAMA 2006;296:1735-41

age 30, severe psoriasis

HR: 3.10

Association Between Tumor Necrosis Factor Inhibitor Therapy and Myocardial Infarction Risk in Patients With Psoriasis.

Wu JJ, Poon KY, Channual JC, Shen AY. Arch Dermatol. 2012 Aug 20:1-7.

• adjusted HR 0.50 vs topical Rx 95% CI, 0.32-0.7

• MI incidence TNF inhibitor/ oral or photoRx /topical:3.05, 3.85, and 6.73 per 1000 patient-years

Results: Unadjusted Cumulative Rates of MACE per 100 Patient-Years (PY)

Based on any Exposure to Therapy or Within 91 Days of Therapy Administration

0.29(0.17, 0.47)

0.31(0.14, 0.62)

0.28(0.19, 0.40)

0.45(0.35, 0.58)

0.36(0.30, 0.43)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

Ustekinumab Infliximab/

Golimumab*Other Biologics** No Biologic All

PSOLAR

8/2558 29/10341 61/13421 114/3181816/5497

0.34(0.23, 0.48)

0.38(0.22, 0.62) 0.33

(0.24, 0.44)

0.36(0.30, 0.43)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

Un

ad

juste

d R

ate

s o

f M

AC

E

per

100 P

Y (

95%

CI)

Exposure Within 91 Days

Any Exposure

Ustekinumab Infliximab/

Golimumab*ADA/ETN** No Biologic All

30/8870 16/4205 43/13167 25/5576 114/31818

*Sponsor biologics, other than ustekinumab, approved for PsO &/or PsA; includes almost exclusively infliximab patients (n=1400); few patients were exposed

to golimumab (n=35). **95% (n=4374) are adalimumab &/or etanercept patients, with the remainder exposed to efalizumab, alefacept, or other non-sponsor

biologic.

0.45(0.29, 0.66)

Psoriasis Patients Treated With Biologics and Methotrexate

Have a Reduced Rate of Myocardial Infarction: A

Collaborative Analysis Using International Cohorts.

Gulliver WP, Young HM, Bachelez H, Randell S, Gulliver S, Al-

Mutairi N.

J Cutan Med Surg. 2016;20:550-554.

IL-17 Mediated Inflammation Promotes Tumor Growth and Progression in the Skin

D. He, et al

PLoS ONE 2012; 7: 1-9

IL-23→↑IL-17→↑tumor growth

Could blocking IL-17 be protective against cancer?

Results: Age and Gender Adjusted Cumulative Rates of Malignancies (excluding NMSC) per 100 Patient-Years (PY) Based on Any Exposure to Therapy (Figure 1)

PSOLAR

Fiorentino D, et al. AAD 2015. P1631.

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Cu

mu

lati

ve R

ate

s p

er

100 P

Y (

95%

CI)

Ustekinumab

(60/12472 PY)

Infliximab*

(41/5176 PY)

ADA/ETN**

(116/15991 PY)

Non-

biologic(57/6749 PY)

All***

(274/40388 PY)

0.81 0.73 0.75 0.680.51

Figure 1. Cumulative Rates of Malignancies

*This group Includes (n=36) patients exposed to golimumab only.

**95.7% (n=4067) are adalimumab &/or etanercept patients, with the remainder exposed to other biologics.

***Adjustment used All population as reference.

4/3/2018

10

• Acitretin 30 mg/d

• 2/19 2 SCCs vs 9/19 18 SCCs

Prevention of skin cancer and reduction

of keratotic skin lesions during acitretin

therapy in renal transplant recipients: a

double-blind, placebo-controlled study.Bavinck JN et al. J Clin Oncol. 1995;13:1933-1938.

Chemoprevention of skin cancer in

xeroderma pigmentosum.Kraemer KH et al. J Dermatol. 1992;19:715-718.

• 121 BCCs or SCCs in 5 patients 2 years prior to Rx

• Isotretinoin 2 mg/kg/d 25 tumors over2 years of Rx

Reasons to Become a Registry Investigator

• Contribute to education/clinical knowledge of the psoriasis

community

• Opportunity to establish a database of your patient population

• Academic recognition and publication opportunities

• Supplement existing insurance fee schedules

– Site compensation is $525 (including $25 for patient) per Enrollment

visit and $350 (including $25 for patient) per biannual Follow Up visit

If you are interested in participating in the Psoriasis

Registry as a research investigator, please email

psoriasis@corrona.org

or visit www.corrona.org

or call 508.408.5432

Become a Registry Research Investigator