PowerPoint Presentation


PRESENTED AT 40TH ANNUAL FALL CLINICAL DERMATOLOGY CONFERENCE, OCTOBER 29–NOVEMBER 1, 2020

Roflumilast Cream (ARQ-151) Improved Itch Severity and Itch-Related 
Sleep Loss in Adults With Chronic Plaque Psoriasis in a Phase 2b Study

INTRODUCTION
• Roflumilast cream (ARQ-151), a potent phosphodiesterase-4 (PDE-4) inhibitor, is 

under investigation as a once-daily topical treatment for plaque psoriasis1,2

• In a randomized, double-blind, phase 2b trial of 331 adults with chronic plaque 
psoriasis, roflumilast cream administered once daily was superior to vehicle cream2

– Primary endpoint of achievement of “clear” or “almost clear” skin based on 
Investigator Global Assessment (IGA) at Week 6 was met
• Roflumilast 0.3%: 28.0% (P<0.001 vs vehicle)
• Roflumilast 0.15%: 22.8% (P=0.004 vs vehicle)
• Vehicle: 8.3%

– Treatment-related adverse events (AEs), including application site pain, were 
uncommon and the frequency was similar in all groups

• Here we report the effect of roflumilast cream on itch, a highly prevalent and 
frequently bothersome symptom of chronic plaque psoriasis that negatively impacts 
quality of life,3 assessed using patient-reported outcome (PRO) measures in this study

OBJECTIVE
• To assess the effect of roflumilast cream on various PROs related to itch

METHODS
• Design: parallel-group, randomized, double-blind, vehicle-controlled phase 2b study 

(ClinicalTrials.gov NCT03638258; Figure 1)2

• Location: 30 sites in the United States and Canada

CONCLUSIONS
• Once-daily roflumilast cream demonstrated significant improvement in reducing itch in 

patients with psoriasis compared with vehicle cream
– Patients reported a rapid and clinically significant reduction in the severity and 

burden of itch
– Significant itch reduction occurred by Week 2 and continued with further reductions 

through Week 12
– In a subgroup of patients with greater severity of itch at baseline (WI-NRS ≥6), more than 

half of the patients had a substantial (≥4-point) reduction in itch by Week 6, and the 
response rate continued to increase through Week 12

– Reduction in itch resulted in significant improvement in sleep loss by Week 6
• Roflumilast cream was well-tolerated and application site pain was uncommon and similar 

to vehicle

Table 1. Baseline Characteristics
Roflumilast 0.3%

(n=109)
Roflumilast 0.15%

(n=113)
Vehicle
(n=109)

Age, mean (SD), years 51.7 (14.1) 54.4 (14.2) 55.5 (13.5)
Sex, male, n (%) 56 (51.4) 62 (54.9) 67 (61.5)
Race, n (%)

White 82 (75.2) 95 (84.1) 92 (84.4)
Black 12 (11.0) 10 (8.8) 7 (6.4)
Multiple/other 15 (13.8) 8 (7.1) 10 (9.2)

Psoriasis-affected BSA, 
mean (SD), %

6.3 (4.0) 6.4 (3.9) 6.4 (3.6)

IGA score
2 (mild), % 15.6 15.9 10.1
3 (moderate), % 77.1 73.5 81.7
4 (severe), % 7.3 10.6 8.3

PASI, mean score (SD) 7.7 (3.6) 8.0 (3.9) 7.6 (3.1)
WI-NRS score ≥6, n (%) 71 (65.1) 62 (54.9) 64 (58.7)
WI-NRS, mean score* (SD) 6.1 (2.7) 5.6 (3.1) 5.9 (2.9)
PSD Item 1, Itch Severity,* 
mean score (SD)

5.5 (2.8) 5.3 (3.1) 5.5 (3.0)

PSD Item 2, Itch Burden,* 
mean score (SD)

5.2 (3.0) 5.2 (3.3) 5.5 (3.2)

Itch-Related Sleep Loss NRS,* mean 
score (SD)

2.9 (3.2) 3.0 (3.2) 3.4 (3.2)

Data are presented for intent-to-treat population. *Scale of 0 (none) to 10 (worst). BSA: body surface area; IGA: Investigator Global 
Assessment; NRS: numeric rating scale; PASI: Psoriasis Area and Severity Index; PSD: Psoriasis Symptom Diary; SD: standard deviation; 
WI-NRS: Worst Itch Numeric Rating Scale.

In a phase 2b study, roflumilast cream, an investigational once-daily, nonsteroidal topical 
PDE-4 inhibitor, was effective in achieving “clear” or “almost clear” skin and improving itch and 

itch-related sleep loss in patients with chronic plaque psoriasis

REFERENCES
1. Papp KA, et al. J Drugs Dermatol 2020;19:734-740. 
2. Lebwohl MG, et al. N Engl J Med 2020;383:229-239. 
3. Naegeli AN, et al. Int J Dermatol 2015;54:715-722. 
4. Lebwohl M, et al. Int J Dermatol 2014;53:714-722. 
5. Strober BE, et al. Value Health 2013;16:1014-1022. 
6. Strober B, et al. Int J Dermatol 2016;55:e147-e155. 
7. Kimball AB, et al. Br J Dermatol 2016;175:157-162.

ACKNOWLEDGEMENTS
• This study was supported by Arcutis Biotherapeutics, Inc.
• Thank you to the investigators and their staff for their participation in the trial
• We are grateful to the study participants and their families for their time and commitment
• Writing support was provided by Aleksandra Adomas, PhD, CMPP, Touch Scientific, Philadelphia, PA, 

and funded by Arcutis Biotherapeutics, Inc.

DISCLOSURES
LSG, MGL, KAP, MJG, LHK, ZDD, SEK, DMP, JA-L, and DPT: Investigator, consultant, and/or advisory board 
member for Arcutis Biotherapeutics, Inc. ZDD has received grant support from Arcutis Biotherapeutics, Inc. 
KS, RCH, LN, and DRB: Employees of Arcutis Biotherapeutics, Inc. HW has a patent application relevant to this work.

• Itch was assessed at baseline and Weeks 2, 4, 6, 8, and 12 using PRO measures:
– Worst Itch Numeric Rating Scale (WI-NRS)3 assessed the worst itch
– Psoriasis Symptom Diary (PSD) Items 1 and 24-6 assessed burden and severity 

of itch 
– Itch-Related Sleep Loss NRS assessed intensity of sleep loss
– All PRO measures assessed itch over the previous 24 hours and were rated on 

a scale from 0 (no impact) to 10 (as bad as it can be)

RESULTS
• In total, 331 patients were randomized to roflumilast 0.3% (n=109), roflumilast 0.15% 

(n=113), or vehicle (n=109)2

• Baseline characteristics are presented in Table 1

Table 2. Summary of AEs

TEAE, n (%)
Roflumilast 0.3%

(n=109)
Roflumilast 0.15%

(n=110)
Vehicle
(n=107)

Patients with any TEAE 42 (38.5) 30 (27.3) 32 (29.9)
Patients with any treatment-
related TEAE

7 (6.4) 3 (2.7) 7 (6.5)

Patients with any SAEa 1 (0.9) 1 (0.9) 2 (1.9)
Patients who discontinued study 
due to AEb

1 (0.9) 0 2 (1.9)

Most common TEAE (>2% of 
patients in any group)

Upper respiratory tract infection 
(including viral)

9 (8.3) 8 (7.3) 4 (3.7)

Nasopharyngitis 4 (3.7) 3 (2.7) 4 (3.7)
Application site pain 2 (1.8) 1 (0.9) 3 (2.8)
Sinusitis 3 (2.8) 0 0
Urinary tract infection 0 3 (2.7) 1 (0.9)

aRoflumilast 0.3%: worsening of chest pain in a patient with history of myocardial infarction; roflumilast 0.15%: melanoma (not in treatment
area); vehicle group: acute infarction of left basal ganglia, spontaneous miscarriage. bRoflumilast 0.3%: onset of worsening psoriasis;
vehicle: mood swings, contact dermatitis. Data are presented for safety population. AE: adverse event; SAE: serious adverse event; 
TEAE: treatment-emergent adverse event.

• Treatment-emergent AEs were uncommon in this study and were similar across treatment 
groups (Table 2)2

• More patients discontinued the study due to an AE in the vehicle group than in the 
roflumilast groups

• Rates of application site pain were low and similar to vehicle
• 97% of AEs were rated mild or moderate

Figure 2. WI-NRS Score: “What was the worst level of itch over the past 24 hours?”

Data are presented for intent-to-treat population. Missing data imputed using linear interpolation and last observation carried forward 
where linear interpolation was not computationally possible. LS: least squares; WI-NRS: Worst Itch Numeric Rating Scale. 

*Nominal P<0.05 vs vehicle

Assessed on a scale from 0 (no itch) to 10 (worst imaginable itch) 

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8 Week 12

LS
 M

ea
n 

Ch
an

ge
 in

 
W

I-
N

RS
 S

co
re

*
*

*
* *

*
*

* * *

• Both roflumilast doses showed similar improvements in WI-NRS score and mean change 
from baseline in WI-NRS score was significantly superior to vehicle throughout the trial 
(P≤0.002; Figure 2)

• Previous studies have shown that a 4-point change is optimal for demonstrating a clinically 
meaningful itch response in patients with moderate to severe plaque psoriasis7

• Among patients with a WI-NRS score ≥6 at baseline (n=197/331), rates of achievement of a 
≥4-point reduction from baseline in WI-NRS score were significantly greater with roflumilast 
0.3% vs vehicle at all timepoints (P≤0.034), and significantly greater with roflumilast 0.15% vs 
vehicle at Weeks 6 and 12 (P≤0.012; Figure 3)

Figure 3. Proportion of Patients With a WI-NRS Score ≥6 at Baseline Who Achieved      
a ≥4-Point Reduction From Baseline in WI-NRS Score

WI-NRS assessed the worst itch over the past 24 hours on a scale ranging from 0 (no itch) to 10 (worst imaginable itch). Data are 
presented for intent-to-treat population. Missing data imputed using linear interpolation and last observation carried forward 
where linear interpolation was not computationally possible. WI-NRS: Worst Itch Numeric Rating Scale.

• Robust improvements in severity of itch based on Item 1 of the PSD were observed for both roflumilast 0.3% 
and 0.15% at Weeks 2 through 12 (P≤0.012 vs vehicle; Figure 4)

Figure 4. PSD Item 1: “How severe was your psoriasis-related itching over the past 24 hours?”

Data are presented for intent-to-treat population. Missing data imputed using linear interpolation and last observation carried forward where linear 
interpolation was not computationally possible. LS: least squares; PSD: Psoriasis Symptom Diary.

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8 Week 12

LS
 M

ea
n 

Ch
an

ge
 in

 
PS

D
 It

em
 1

*

*
*

* *

*
*

*
*

*

*Nominal P<0.05 vs vehicle

Assessed severity of itch on a scale from 0 (no itching) 
to 10 (as bad as you can imagine)

• Robust improvements in burden of itch based on Item 2 of the PSD were observed for both roflumilast 0.3% and 
0.15% at Weeks 2 through 12 (P≤0.012 vs vehicle; Figure 5)

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8 Week 12

LS
 M

ea
n 

Ch
an

ge
 in

 
PS

D
 It

em
 2

*
*

* *

*
*

* *

• Improvements in the Itch-Related Sleep Loss score were significantly greater with both roflumilast doses vs 
vehicle at Weeks 6 through 12 (P≤0.022; Figure 6)

-4

-3

-2

-1

0
Baseline Week 2 Week 4 Week 6 Week 8 Week 12

LS
 M

ea
n 

Ch
an

ge
 in

 It
ch

-R
el

at
ed

 
Sl

ee
p 

Lo
ss

 N
RS

 S
co

re

*
* *

*
* *

*Nominal P<0.05 vs vehicle

0

20

40

60

80

Week 2 Week 4 Week 6 Week 8 Week 12

Pa
ti

en
ts

, %

* *
* *

*

*

*

Roflumilast 0.15% (n=62) Vehicle (n=64)Roflumilast 0.3% (n=71)

I
M
P
R
O
V
E
M
E
N
T

I
M
P
R
O
V
E
M
E
N
T

I
M
P
R
O
V
E
M
E
N
T

Figure 5. PSD Item 2: “How bothered were you by your psoriasis-related itching over the 
past 24 hours?”

Data are presented for intent-to-treat population. Missing data imputed using linear interpolation and last observation carried forward where linear 
interpolation was not computationally possible. LS: least squares; PSD: Psoriasis Symptom Diary.

*Nominal P<0.05 vs vehicle

Assessed burden of itch on a scale from 0 (not bothered at all) 
to 10 (as bothered as you can imagine)

Figure 6. Itch-Related Sleep Loss NRS Score: “How intense was your itch-related sleep loss over the 
past 24 hours?” 

Data are presented for intent-to-treat population. Missing data imputed using linear interpolation and last observation carried forward where linear 
interpolation was not computationally possible. LS: least squares; NRS: numeric rating scale.

*Nominal P<0.05 vs vehicle

Assessed on a scale from 0 (no itch-related sleep loss) 
to 10 (sleep loss as bad as it can be) 

Roflumilast 0.3% (n=109) Roflumilast 0.15% (n=113) Vehicle (n=109)

*

*

Figure 1. Study Design

BSA: body surface area; IGA: Investigator Global Assessment; NRS: Numeric Rating Scale; QD: once daily; PASI: Psoriasis 
Area and Severity Index; PSD: Psoriasis Symptom Diary; WI-NRS: Worst Itch Numeric Rating Scale.

Roflumilast 
cream

0.3% QD

Roflumilast 
cream

0.15% QD

Vehicle
QD

ENDPOINTS
• Primary: IGA “clear or “almost 

clear” at Week 6
• Secondary:

– IGA “clear” or “almost 
clear” skin + ≥2-grade 
improvement

– PASI-75 and PASI-90
– Intertriginous-IGA “clear” 

or “almost clear” skin + 
≥2-grade improvement

– WI-NRS 
– PSD
– Itch-Related Sleep Loss NRS

• Safety and tolerability
12 weeks

Ra
nd

om
iz

at
io

n

1:1:1

N=331

ELIGIBILITY
• Diagnosis of 

at least mild 
plaque psoriasis

• Age ≥18 years
• 2-20% BSA

Linda Stein Gold,1 Mark G. Lebwohl,2 Kim A. Papp,3 Melinda J. Gooderham,4 Leon H. Kircik,5 Zoe D. Draelos,6 Steven E. Kempers,7 David M. Pariser,8
Javier Alonso-Llamazares,9 Darryl P. Toth,10 Kathleen Smith,11 Robert C. Higham,11 Lynn Navale,11 Howard Welgus,11 David R. Berk11
1Henry Ford Medical Center, Detroit, MI, USA; 2Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 4SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 
5Icahn School of Medicine at Mount Sinai, New York, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY, USA; 6Dermatology Consulting Services, High Point, NC, USA; 7Minnesota Clinical Study Center, Fridley, MN, USA; 
8Department of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA, USA; 9Driven Research LLC, Coral Gables, FL, USA; 10XLR8 Medical Research, Probity Medical Research, Windsor, ON, Canada; 11Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

Roflumilast 0.3% (n=109) Roflumilast 0.15% (n=113) Vehicle (n=109)

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P
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Roflumilast 0.3% (n=109) Roflumilast 0.15% (n=113) Vehicle (n=109)

I
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E
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Roflumilast 0.3% (n=109) Roflumilast 0.15% (n=113) Vehicle (n=109)
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	Roflumilast Cream (ARQ-151) Improved Itch Severity and Itch-Related Sleep Loss in Adults With Chronic Plaque Psoriasis in a Phase 2b Study
















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