INTRODUCTION 
• Patients with moderate plaque psoriasis (i.e., 5% to 10% psoriasis-involved body surface area [BSA]1) 

often receive no treatment or are undertreated with topical monotherapy.2,3 

• Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor,4 was shown to be effective and 
demonstrated acceptable tolerability in patients with moderate to severe psoriasis (BSA ≥10%) in the 
Effi cacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) phase III clinical trial 
program.5,6

• Evaluating Apremilast in a Phase IV Trial of Effi cacy and Safety in Patients With Moderate Plaque 
Psoriasis (UNVEIL) (ClinicalTrials.gov: NCT02425826) is the fi rst prospective randomized, placebo 
(PBO)-controlled trial to demonstrate the clinical effi cacy and safety of a systemic treatment (apremilast) 
in systemic- and biologic-naive patients with moderate plaque psoriasis. Apremilast 30 mg twice daily 
(APR) was clinically effective and well tolerated during the 16-week, double-blind, PBO-controlled phase.

• The effi cacy and safety results of the open-label APR treatment phase up to Week 52 are presented.

METHODS
Patients
Key Inclusion Criteria
• Males or females ≥18 years of age

• Chronic plaque psoriasis for ≥6 months before screening

• Moderate plaque psoriasis at screening and baseline as defi ned by BSA of 5% to 10% and static 
Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 
5 (very severe)

• No prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other 
condition that could affect the assessment of psoriasis 

Key Exclusion Criteria
• Infl ammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis

• Topical therapy within 2 weeks or phototherapy within 4 weeks of randomization

Study Design
• UNVEIL is a phase IV, multicenter, randomized, PBO-controlled, double-blind study (Figure 1).

• Patients were randomized (2:1) to receive APR or PBO during Weeks 0 to 16; patients in the PBO group 
were switched to APR at Week 16.

• All patients continued taking APR through Week 52.

Figure 1. The UNVEIL Study Design

Primary end point:
Mean percentage 

change in PGAxBSA at Week 16 

RA
N

D
O

M
IZ

E
1:

2§SCREEN*

Placebo (n=73)

Placebo-Controlled 
Phase

Apremilast 30 mg BID (n=148)

Open-label
Treatment Phase 

Safety 
Observation

Apremilast 30 mg BID‡ (n=64)

–5 Weeks Week 16 Week 52 Week 0 Week 56

ClinicalTrials.gov: NCT02425826
*Screening up to 35 days before randomization.
§All doses were titrated over the fi rst week of treatment.
‡At Week 16, all placebo patients were switched to open-label apremilast 30 mg BID (with dose titration) through Week 52.
BID=twice daily; PGAxBSA=product of the static Physician’s Global Assessment and body surface area involvement.

METHODS (cont’d)
Effi cacy Assessments
Primary Effi cacy 
• The primary effi cacy end point was the mean percentage change from baseline at Week 16 in PGAxBSA, 

which represents the product of sPGA and BSA scores. 
• Overall BSA affected by psoriasis is estimated based on the patient’s palm area, which equates to 

approximately 1% of total BSA. 
• For the 6-point sPGA, for plaques in all involved areas, the severity of erythema, scaling, and plaque 

elevation each were scored; scores were averaged and rounded to the nearest whole number.7

Secondary Effi cacy 
• Proportions of patients achieving:

 – ≥75% reduction from baseline in PGAxBSA score (PGAxBSA-75) 
 – sPGA response, defi ned as a score of 0 (clear) or 1 (almost clear)

QOL
• Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI).8

Safety Assessments
• Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and 

complete physical examinations.

Statistical Analysis
• Effi cacy and QOL assessments were conducted for the intent-to-treat (ITT) population, which included 

all randomized patients; safety assessments were conducted in all randomized patients who received 
≥1 dose of study medication.

• Mean percentage change from baseline in PGAxBSA and change from baseline in DLQI total score at 
Week 16 were compared between APR and PBO using a 2-sided analysis of covariance model with 
treatment and site as factors and baseline value as covariate. 

• PGAxBSA-75 and sPGA responses at Week 16 were evaluated with 2-sided Cochran-Mantel-Haenszel tests 
stratifi ed by site.

• Effi cacy and QOL parameters at Week 52 were evaluated descriptively.
 – Week 16 and Week 52 APR/APR analyses were performed with the ITT population.
 – Week 52 PBO/APR analyses were performed with the modifi ed ITT population (all patients who 

entered the APR extension phase).
• The last-observation-carried-forward methodology was used to impute missing values.
• Safety assessments were summarized using frequencies and percentages.

RESULTS
Patients
• A total of 221 patients were randomized to study treatment and constitute the ITT population; 185 patients 

(84%) completed the PBO-controlled phase (Weeks 0 to 16) and 136/185 patients (74%) completed the 
APR treatment phase (Weeks 16 to 52).

• Demographics and baseline disease characteristics were generally similar between treatment groups 
(Table 1).

 – At baseline, mean DLQI total scores were comparable between treatment groups, and the mean 
pruritus visual analog scale score was slightly higher in the PBO group.

Table 1. Patient Demographics and Baseline Disease Characteristics

Characteristic
PBO
n=73

APR
n=148 

Age, mean (SD), years 51.1 (13.7) 48.6 (15.4)
Male, n (%) 41 (56.2) 74 (50.0)
Body mass index, mean (SD), kg/m2 30.8 (6.5) 30.5 (7.4)
Duration of psoriasis, mean (SD), years 13.9 (12.6) 17.5 (13.9)
PGAxBSA score, mean (SD) 21.6 (5.9) 21.8 (5.3)
BSA, mean (SD), % 7.1 (1.8) 7.2 (1.6)
PASI score (0–72), mean (SD) 8.0 (3.2) 8.2 (4.0)
DLQI total score, mean (SD) 11.1 (6.5) 11.0 (6.5)
Prior topical therapy, n (%) 59 (80.8) 122 (82.4)
PASI=Psoriasis Area and Severity Index.

RESULTS (cont’d)
• At Week 16, signifi cantly greater improvement in PGAxBSA occurred in patients receiving APR vs. PBO 

(Figure 2).

• At Week 52, improvement was maintained in the APR/APR group and emerged in the PBO/APR group 
after switching to APR. 

Figure 2. Mean Percentage Change in PGAxBSA at Week 16 and Week 52

10

0

-10

-20

-30

-40

-50

-60

-70

M
ea

n 
Pe

rc
en

ta
ge

 C
ha

ng
e 

Fr
om

 
Ba

se
lin

e 
in

 P
GA

xB
SA

 S
co

re

Week 16 Week 52
PBO
n=73

APR
n=147

PBO/APR
n=64

APR/APR
n=147

–10.2

–48.1
* –42.2

–49.0

*P<0.0001.
Error bars represent 95% confi dence intervals (CIs).

• Signifi cantly more patients treated with APR achieved PGAxBSA-75 response at Week 16 vs. PBO 
(Figure 3). 

• PGAxBSA-75 response was maintained in the open-label APR treatment phase.

Figure 3. Patients Achieving PGAxBSA-75 Response at Week 16 and Week 52

Week 52

PBO/APR
n=64

APR/APR
n=147

12.3

*
35.4

45.3

37.4

60

50

40

30

20

10

0Pe
rc

en
ta

ge
 o

f P
at

ie
nt

s 
Ac

hi
ev

in
g 

PG
Ax

BS
A-

75
 R

es
po

ns
e

Week 16

PBO
n=73

APR
n=147

*P=0.0001.
Response defi ned as ≥75% reduction from baseline in PGAxBSA score. Error bars represent 95% CIs.

• Signifi cantly more patients treated with APR achieved an sPGA score of 0 or 1 at Week 16 vs. PBO 
(Figure 4). 

• Long-term sPGA response was maintained with APR treatment in the open-label treatment phase.

Figure 4. Patients Achieving sPGA Score of 0 (Clear) or 1 (Almost Clear) at Week 16 
and Week 52

Week 52

PBO/APR
n=64

APR/APR
n=148

9.6

*
30.4

35.9

29.1

50

0

Pe
rc

en
ta

ge
 o

f P
at

ie
nt

s 
Ac

hi
ev

in
g

sP
GA

 S
co

re
 o

f 0
 o

r 
1

Week 16

40

30

20

10

PBO
n=73

APR
n=148

*P<0.0001.
Error bars represent 95% CIs.

RESULTS (cont’d)
• Improvement in DLQI was signifi cantly greater with APR than PBO at Week 16 (Figure 5).

• DLQI improvement was maintained in patients continuing on APR for up to 52 weeks, and developed 
after patients were switched from PBO to APR.

Figure 5. Mean Change in DLQI at Week 16 and Week 52 

0

M
ea

n 
Ch

an
ge

 F
ro

m
 B

as
el

in
e 

in
 D

LQ
I T

ot
al

 S
co

re

Week 16 Week 52

-1

-2

-3

-4

-5

-6

-7

PBO
n=71

APR
n=144

PBO/APR
n=63

APR/APR
n=144

–2.4

–4.8
*

–5.1

–4.3

-8

*P=0.0008.
Error bars represent 95% CIs.

• Most AEs were mild or moderate (Table 2). 

• The most common AEs (reported in ≥5% patients in either treatment group during the PBO-controlled 
period) included diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, 
and vomiting.  

Table 2. Overview of Adverse Events
Weeks 0 to 16 Weeks 0 to 52

Patients, n (%)

PBO
n=73

APR
n=147 

APR*
n=211

n (%)
EAIR/100

Pt-Yrs n (%)
EAIR/100

Pt-Yrs n (%)
EAIR/100

Pt-Yrs

≥1 AE 35 (47.9) 262.3 92 (62.6) 459.8 142 (67.3) 242.7

≥1 Serious AE 0 (0) 0.0 3 (2.0) 7.4 10 (4.7) 6.8

≥1 Severe AE 1 (1.4) 4.9 3 (2.0) 7.5 5 (2.4) 3.4

AE leading to drug withdrawal 3 (4.1) 14.5 5 (3.4) 12.4 14 (6.6) 9.6

Most common AEs§, n (%)

Diarrhea 12 (16.4) 63.7 43 (29.3) 139.8 59 (28.0) 53.8

Nausea 7 (9.6) 35.4 26 (17.7) 73.7 40 (19.0) 31.8

Headache 8 (11.0) 42.4 30 (20.4) 89.2 32 (15.2) 24.9

Nasopharyngitis 2 (2.7) 9.8 5 (3.4) 12.5 22 (10.4) 16.2

Upper respiratory tract infection 3 (4.1) 14.8 10 (6.8) 25.2 15 (7.1) 10.7

Vomiting 2 (2.7) 9.7 9 (6.1) 22.9 12 (5.7) 8.4

Decreased appetite 4 (5.5) 19.6 6 (4.1) 15.3 11 (5.2) 7.7

*Includes all patients exposed to APR, including those initially randomized to PBO and switched at Week 16 to APR. §Reported by ≥5% of patients in any 
treatment group; listed in order of incidence over 52-week period. Pt-yrs=patient-years. EAIR/100 pt-yrs=exposure-adjusted incidence rate per 100 patient-years, 
calculated as (number of events*100)/(total exposure time [in years] of safety population). The exposure time for a patient without a specifi c event is the 
treatment duration, whereas the exposure time for a patient with the specifi c event is the treatment duration up to the start date (inclusive) of the fi rst 
occurrence of the specifi c event. 

CONCLUSIONS
• APR was clinically effective in systemic- and biologic-naive patients with moderate plaque psoriasis 

(BSA of 5% to 10%).

• APR signifi cantly improved PGAxBSA score, PGAxBSA-75 response rate, sPGA 0 or 1 response rate, and 
DLQI total score at Week 16 compared with PBO.

• Clinical responses were maintained with continued APR treatment through Week 52 and emerged in 
patients who switched from PBO to APR at Week 16.

• The incidence of AEs, based on EAIR per 100 patient-years, did not increase with longer exposure to APR.

• Safety and tolerability were consistent with previous studies5,6; no new safety or tolerability issues were 
observed up to 52 weeks.

REFERENCES
1. Menter A, et al. J Am Acad Dermatol. 2011;65:137-174.

2. Armstrong AW, et al. JAMA Dermatol. 2013;149:1180-1185. 

3. Lebwohl MG, et al. J Am Acad Dermatol. 2014;70:871-881. 

4. Schafer PH, et al. Cell Signal. 2014;26:2016-2029.

5. Papp K, et al. J Am Acad Dermatol. 2015;73:37-49.

6. Paul C, et al. Br J Dermatol. 2015;173:1387-1399.

7. Walsh JA, et al. J Am Acad Dermatol. 2013;69:931-937. 

8. Finlay AY, et al. Clin Exp Dermatol. 1994;19:210-216.

ACKNOWLEDGMENTS
The authors acknowledge fi nancial support for this study from Celgene Corporation. The authors received 
editorial support in the preparation of this report from Amy Shaberman, PhD, of Peloton Advantage, LLC, 
Parsippany, NJ, USA, sponsored by Celgene Corporation, Summit, NJ, USA. The authors, however, directed 
and are fully responsible for all content and editorial decisions for this poster.

CORRESPONDENCE
Bruce Strober – brucestrober30@me.com

DISCLOSURES
BS: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene Corporation, Dermira, Eli Lilly, Forward 
Pharma, Janssen, LEO Pharma, Maruho, Medac, Novartis, Pfi zer, Stiefel/GlaxoSmithKline, Sun Pharma, and 
UCB – honoraria as a consultant and advisory board member; AbbVie, Amgen, Celgene Corporation, Eli 
Lilly, Janssen, Merck, Novartis, and Pfi zer – payments (to the University of Connecticut) as an investigator; 
CORRONA Psoriasis Registry – fees as a scientifi c director; AbbVie and Janssen – grant support (to the 
University of Connecticut for Fellowship Program). JB: AbbVie, Amgen, Boehringer Ingelheim, Celgene 
Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfi zer, and Valeant – advisory board member, speaker, 
consultant, and/or research support; Sun Pharma – consultant. ML: Mount Sinai, which receives funds from 
Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, MedImmune/
AstraZeneca, Novartis, Pfi zer, and ViDac. LSG: Celgene Corporation, LEO Pharma, Novartis, Pfi zer, and Stiefel/
GlaxoSmithKline – investigator and/or consultant. JMJ: AbbVie, Amgen, Celgene Corporation, Dermira, 
Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfi zer, Promius, and TopMD – research, 
honoraria, consulting, and/or other support. JG & EL: Celgene Corporation – employment. KCD: AbbVie, 
Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Centocor/Janssen, Eli Lilly, Novartis, 
Pfi zer, Regeneron, Stiefel, and XenoPort – consultant, steering committee member, advisory board member, 
has received grants, and/or has received honoraria.

Presented at: the 2017 Fall Clinical Dermatology Conference; October 12–15, 2017; Las Vegas, NV.

Effi cacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis With Lower BSA (UNVEIL Phase IV Study)
Bruce Strober, MD1; Jerry Bagel, MD2; Mark Lebwohl, MD3; Linda Stein Gold, MD4; J. Mark Jackson, MD5; Joana Goncalves, MD6; Eugenia Levi, PharmD6; Kristina Callis Duffi n, MD7 
1University of Connecticut, Farmington, CT, and Probity Medical Research, Waterloo, ON, Canada; 2Treatment Center of Central New Jersey, East Windsor, NJ; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4Henry Ford Health System, West Bloomfi eld, MI; 5University of Louisville, Forefront Dermatology, Louisville, KY; 
6Celgene Corporation, Summit, NJ; 7University of Utah, Salt Lake City, UT


	FC17PosterCelgeneStroberEfficacyUNVEILStudy.pdf