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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
or visit www.corrona.org
or call 508.408.5432
Become a Registry Research Investigator