Kim Papp, MD, PhD,1 Jacek C. Szepietowski, MD, PhD,2 Leon Kircik, MD,3 Darryl Toth, MD,4  
Michael E. Kuligowski, MD, PhD, MBA,5 May E. Venturanza, MD,5 Kang Sun, PhD,5 Eric L. Simpson, MD6

Background
 ● Atopic dermatitis (AD) is a chronic, inflammatory skin disease that greatly impacts 
patients’ quality of life1,2

 ● Janus kinases (JAKs) modulate inflammatory cytokines involved in the pathogenesis  
of AD3 and may also directly modulate itch4

 ● Ruxolitinib (RUX) is a potent, selective inhibitor of JAK1 and JAK25 
 ● In a phase 2 study (NCT03011892), RUX cream provided strength-dependent efficacy 
in patients with AD and a safety profile similar to vehicle6

Objectives
 ● To report efficacy and safety of RUX cream in patients with AD in two phase 3 studies 
(TRuE-AD1 [NCT03745638] and TRuE-AD2 [NCT03745651])

Methods
Patients and Study Design

 ● Eligible patients were aged ≥12 years with AD for ≥2 years, an Investigator’s Global 
Assessment (IGA) score of 2 or 3, and 3% to 20% affected body surface area

 ● Key exclusion criteria were unstable course of AD, other types of eczema, 
immunocompromised status, use of AD systemic therapies during the washout period 
and during the study, use of AD topical therapies (except bland emollients) during the 
washout period and during the study, and any serious illness/medical condition that 
could interfere with study conduct, interpretation of data, or patients’ well-being

 ● TRuE-AD1 and TRuE-AD2 had identical study designs (Figure 1)
 – In both studies, patients were randomized (2:2:1) to either of 2 RUX cream  
strength regimens (0.75% twice daily [BID], 1.5% BID) or vehicle cream for 8 weeks 
of double-blind treatment
 – Patients on RUX cream could subsequently continue treatment for 44 weeks; patients 
initially randomized to vehicle were re-randomized 1:1 to either RUX cream regimen

Figure 1. Study Design

Vehicle-controlled period
 (8 continuous weeks)

Long-term safety 
(treat as needed for 44 weeks)

Recurrence of 
lesions 

Clearance of 
lesions 

Patients initially
randomized to RUX

remain on their regimen 

Patients on vehicle
randomized 1:1 to

0.75% RUX or 1.5% RUX

1.5% RUX BID
(n=~240 in each study)

0.75% RUX BID
(n=~240 in each study)

Patients 
Randomized

2:2:1

Vehicle
(n=~120 in each study)

RUX*

Visits every 4 weeks

Week 52Day 1 Week 8
AD, atopic dermatitis; BID, twice daily; BSA, body surface area; RUX, ruxolitinib.
*  Patients will self-evaluate recurrence of lesions between study visits and will treat lesions with active AD (≤20% BSA). If lesions clear between study visits, patients will stop 

treatment 3 days after lesion disappearance. If new lesions are extensive or appear in new areas, patients will contact the investigator to determine if an additional visit is needed.

Assessments
 ● The primary endpoint was the proportion of patients achieving IGA-treatment success 
(IGA-TS; score of 0/1 with ≥2-grade improvement from baseline) at Week 8 

 ● The main secondary endpoints were the proportion of patients achieving ≥75% 
improvement in Eczema Area and Severity Index score vs baseline (EASI-75) and the 
proportion of patients with a ≥4-point improvement in itch numerical rating scale (NRS) 
score from baseline to Week 8

Statistical Analyses
 ● The primary and main secondary endpoints were analyzed by logistic regression using 
the intent-to-treat population 

 ● All other secondary endpoints were analyzed using descriptive statistics
 ● The efficacy population consisted of 631 patients for TRuE-AD1 (all randomized 
patients) and 577 patients for TRuE-AD2 (vehicle, n=118; 0.75% RUX, n=231;  
1.5% RUX, n=228) 

 ● All patients who applied the study cream at least once (same as all randomized 
patients) were included in the safety population in both studies

1K. Papp Clinical Research and Probity Medical Research, 
Waterloo, ON, Canada; 2Department of Dermatology, 
Venereology and Allergology, Wroclaw Medical University, 
Wroclaw, Poland; 3Icahn School of Medicine at Mount Sinai, 
New York, NY, USA; 4XLR8 Medical Research and Probity 
Medical Research, Windsor, ON, Canada; 5Incyte Corporation, 
Wilmington, DE, USA; 6Oregon Health and Science University, 
Portland, OR, USA

Presented at the

Fall Clinical Dermatology Conference
October 29 – November 1, 2020

Results
Patients

 ● In TRuE-AD1, 631 patients were randomized, and 558 (88.4%) completed treatment in 
the 8-week vehicle-controlled period

 ● In TRuE-AD2, 618 patients were randomized, and 561 (90.8%) completed treatment in 
the 8-week vehicle-controlled period

 ● Distribution of baseline demographics and clinical characteristics was similar across 
treatment groups (Table 1)

Table 1. Patient Demographics and Baseline Clinical Characteristics
TRuE-AD1 TRuE-AD2

Vehicle  
(n=126)

0.75% RUX 
(n=252)

1.5% RUX  
(n=253)

Vehicle  
(n=124)

0.75% RUX 
(n=248)

1.5% RUX  
(n=246)

Age, median (range), y 31.5 (12–82) 34.0 (12–85) 30.0 (12–77) 37.5 (12–82) 33.0 (12–81) 32.0 (12–85)
12–17, n (%) 23 (18.3) 53 (21.0) 47 (18.6) 22 (17.7) 55 (22.2) 45 (18.3)
≥18, n (%) 103 (81.7) 199 (79.0) 206 (81.4) 102 (82.3) 193 (77.8) 201 (81.7)

Female, n (%) 79 (62.7) 154 (61.1) 158 (62.5) 80 (64.5) 150 (60.5) 150 (61.0)
Race, n (%)*

White 85 (67.5) 171 (67.9) 175 (69.2) 84 (67.7) 174 (70.2) 178 (72.4)
Black 29 (23.0) 55 (21.8) 56 (22.1) 32 (25.8) 63 (25.4) 57 (23.2)
Other 12 (9.5) 26 (10.3) 21 (8.3) 8 (6.5) 11 (4.4) 11 (4.5)

Region, n (%)
North America 88 (69.8) 176 (69.8) 176 (69.6) 84 (67.7) 166 (66.9) 165 (67.1)
Europe 38 (30.2) 76 (30.2) 77 (30.4) 40 (32.3) 82 (33.1) 81 (32.9)

BSA, mean ± SD, % 9.2±5.1 9.9±5.4 9.3±5.2 10.1±5.8 10.1±5.3 9.9±5.4
Baseline EASI, mean ± SD 7.4±4.3 8.2±4.8 7.9±4.6 8.2±5.2 8.1±5.0 7.8±4.9
Baseline IGA, n (%)

2 31 (24.6) 61 (24.2) 60 (23.7) 33 (26.6) 64 (25.8) 63 (25.6)
3 95 (75.4) 191 (75.8) 193 (76.3) 91 (73.4) 184 (74.2) 183 (74.4)

Itch NRS score, mean ± SD 5.1±2.5 5.1±2.3 5.2±2.5 5.1±2.4 5.2±2.5 4.9±2.5
Itch NRS score ≥4, n (%) 78 (61.9) 156 (61.9) 161 (63.6) 81 (65.3) 168 (67.7) 154 (62.6)
Duration of disease,  
median (range), y

17.9
(1.9–79.1)

14.1
(1.0–68.8)

16.0
(0–69.2)

15.9  
(0.8–70.7)

15.9  
(0.1–68.6)

16.6  
(0–68.8)

Facial involvement, n (%) 52 (41.3) 112 (44.4) 118 (46.6) 41 (33.1) 83 (33.5) 79 (32.1)
BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, numerical rating scale; RUX, ruxolitinib.
* Data missing from 1 patient in the 1.5% RUX group in TRuE-AD1.

Efficacy
 ● Significantly more patients treated with RUX cream regimens vs vehicle demonstrated 
IGA-TS (primary endpoint); responses were time and strength dependent (Figure 2)

 ● Significantly more patients treated with RUX cream achieved EASI-75 vs vehicle; 
responses were time and strength dependent (Figure 3)

 ● Both strengths of RUX cream showed greater improvement in mean percentage 
change in EASI scores vs vehicle; statistical significance was observed at Week 2 and 
later (Figure 4)

 ● Significantly greater reductions in itch NRS scores were observed within 12 hours of 
the first application of RUX cream (1.5%; P<0.05; Figure 5) vs vehicle

 ● Significantly more patients treated with RUX cream demonstrated clinically meaningful 
reduction in itch (≥4-point improvement in itch NRS) vs vehicle (Figure 6)

Figure 2. Proportion of Patients With IGA-TS

Pr
op

or
tio

n 
(S

E)
 o

f 
IG

A 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

60

Pr
op

or
tio

n 
(S

E)
 o

f 
IG

A 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

60

0 2 4 8
Week

0 2 4 8
Week

TRuE-AD1 TRuE-AD2
Vehicle
(n=118)

0.75% RUX
(n=231)

1.5% RUX
(n=228)

Vehicle
(n=126)

0.75% RUX
(n=252)

1.5% RUX
(n=253)

27.3

46.6
53.8
***

25.0

43.4
51.3
***

22.2

42.5

50.0
***

17.3

35.5
39.0
***

3.2
6.3

15.1

4.2
5.9 7.6

IGA, Investigator’s Global Assessment; IGA-TS, Investigator’s Global Assessment-treatment success; RUX, ruxolitinib; SE, standard error.
*** P<0.0001.
†  Defined as patients achieving an IGA score of 0 or 1 with an improvement of ≥2 points from baseline. Patients with missing post-baseline values were imputed as nonresponders 

at Weeks 2, 4, and 8.

Figure 3. Proportion of Patients Achieving EASI-75

Pr
op

or
tio

n 
(S

E)
 o

f 
EA

SI
-7

5 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

70

60

Pr
op

or
tio

n 
(S

E)
 o

f 
EA

SI
-7

5 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

70

60

0 2 4 8
Week

0 2 4 8
Week

TRuE-AD1 TRuE-AD2
Vehicle
(n=118)

0.75% RUX
(n=231)

1.5% RUX
(n=228)

Vehicle
(n=126)

0.75% RUX
(n=252)

1.5% RUX
(n=253)

5.6
14.3

24.6
30.2

51.6
56.0

36.0

58.5 62.1
***

***

4.2
10.2

14.4

25.5

42.0

51.5

31.6

50.4
61.8
***

***

EASI-75, ≥75% improvement in Eczema Area and Severity Index score from baseline; RUX, ruxolitinib; SE, standard error.
*** P<0.0001.
† Patients with missing post-baseline values were imputed as nonresponders at Weeks 2, 4, and 8.

Figure 4. EASI Percentage Change From Baseline

 M
ea

n 
(9

5%
 C

I) 
Pe

rc
en

ta
ge

 C
ha

ng
e

Fr
om

 B
as

el
in

e 
in

 E
AS

I S
co

re
, %

–90
–80
–70
–60
–50
–40

–10
0

–20
–30

 M
ea

n 
(9

5%
 C

I) 
Pe

rc
en

ta
ge

 C
ha

ng
e

Fr
om

 B
as

el
in

e 
in

 E
AS

I S
co

re
, %

–90
–80
–70
–60
–50
–40

–10
0

–20
–30

0 2 4 8
Week

0 2 4 8
Week

TRuE-AD1 TRuE-AD2

Vehicle 0.75% RUX 1.5% RUXVehicle 0.75% RUX 1.5% RUX

***

***
***

***

***

***

–16.1
–23.5

–40.5
–51.9

–68.4 –72.2
–56.6

–71.2 –77.2

***

***
***

***

***

***

–13.5
–21.1

–28.9
–45.6

–65.3
–74.8

–49.5

–66.2
–74.7

EASI, Eczema Area and Severity Index; RUX, ruxolitinib.
*** P<0.0001.

Figure 5. Change From Baseline in Daily Itch NRS Score

 M
ea

n 
Ch

an
ge

 F
ro

m
 B

as
el

in
e

in
 D

ai
ly

 It
ch

 N
RS

 S
co

re

–3.5

–3.0

–2.5

–2.0

–1.5

0

–0.5

–1.0

 M
ea

n 
Ch

an
ge

 F
ro

m
 B

as
el

in
e

in
 D

ai
ly

 It
ch

 N
RS

 S
co

re

B 7 14 21 28

–3.5

–3.0

–2.5

–2.0

–1.5

0

–0.5

–1.0

B 7 14 21 28
Study Day Study Day

TRuE-AD1 TRuE-AD2

Vehicle 0.75% RUX 1.5% RUXVehicle 0.75% RUX 1.5% RUX

–3.39

–2.81

–1.03
***
***

*

–1.09

–2.89

–2.88

******

*

B, baseline; NRS, numerical rating scale; RUX, ruxolitinib.
* P<0.05; *** P<0.0001.

Figure 6. Proportion of Patients With ≥4-Point Improvement in Itch NRS

Pr
op

or
tio

n 
(S

E)
 o

f
Itc

h 
NR

S 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

60

Pr
op

or
tio

n 
(S

E)
 o

f
Itc

h 
NR

S 
Re

sp
on

de
rs

, %
†

0

10

20

30

40

50

60

0 2 4 8
Week

0 2 4 8
Week

TRuE-AD1 TRuE-AD2
Vehicle
(n=80)

0.75% RUX
(n=157)

1.5% RUX
(n=146)

Vehicle
(n=78)

0.75% RUX
(n=156)

1.5% RUX
(n=161)

5.1
11.5

15.4

26.3

38.5 40.4
33.5

51.6
52.2

**

***

5.0
12.5

16.3

27.4

38.2
42.732.2

45.2 50.7
***

***

NRS, numerical rating scale; RUX, ruxolitinib; SE, standard error.
** P<0.001; *** P<0.0001.
† Patients in the analysis had an NRS score ≥4 at baseline. Patients with missing post-baseline values were imputed as nonresponders at Weeks 2, 4, and 8. 

Safety
 ● RUX cream was well tolerated and not associated with clinically significant application 
site reactions (Table 2)

 ● All treatment-related treatment-emergent adverse events (TEAEs) were mild or 
moderate in severity

 ● No TEAEs suggestive of a relationship to bioavailability were observed

Table 2. Treatment-Emergent Adverse Events
TRuE-AD1 TRuE-AD2

Vehicle  
(n=126)

0.75% RUX 
(n=252)

1.5% RUX  
(n=253)

Vehicle  
(n=124)

0.75% RUX 
(n=248)

1.5% RUX  
(n=246)

Patients with TEAE, n (%) 44 (34.9) 74 (29.4) 73 (28.9) 40 (32.3) 73 (29.4) 58 (23.6)

Patients with treatment-related TEAE, 
n (%) 16 (12.7) 15 (6.0) 14 (5.5) 12 (9.7) 8 (3.2) 11 (4.5)

Most common treatment-related 
TEAEs, n (%)

Application site burning 2 (1.6) 0 2 (0.8) 8 (6.5) 2 (0.8) 2 (0.8)

Application site pruritus 2 (1.6) 2 (0.8) 0 4 (3.2) 2 (0.8) 0

Pruritus 2 (1.6) 2 (0.8) 1 (0.4) 0 0 0

Discontinuation due to a TEAE,  
n (%) 5 (4.0) 3 (1.2) 3 (1.2) 3 (2.4) 1 (0.4) 0

Serious TEAE, n (%)* 2 (1.6) 1 (0.4) 2 (0.8) 0 3 (1.2) 1 (0.4)
RUX, ruxolitinib; TEAE, treatment-emergent adverse event.
* No serious TEAEs were related to RUX treatment.

Conclusions
 ● Ruxolitinib cream showed superior efficacy vs vehicle in 
IGA-TS, EASI-75, and ≥4-point reduction in itch NRS score 
in these two phase 3 studies
 ● Application of ruxolitinib cream brought about rapid 
(within 12 hours of initiation of therapy), substantial, and 
sustained reduction in itch  
 ● Ruxolitinib cream demonstrated a dual mode of action: 
antipruritic and anti-inflammatory
 ● No notable safety findings (either local or systemic)  
were associated with treatment, including on sensitive 
skin areas 
 ● The successful outcomes of TRuE-AD1 and TRuE-AD2 
support the potential of ruxolitinib cream as an effective 
and well-tolerated topical treatment for patients with AD

Disclosures
KP has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, 
and/or Steering Committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, 
Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly, 
Galderma, Genentech, Gilead, GlaxoSmithKline, InflaRx, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji 
Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, 
Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB. JCS has served as an advisor for 
AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, and Trevi; has received speaker honoraria from AbbVie, 
Janssen-Cilag, LEO Pharma, Novartis, Sanofi-Genzyme, Sun Pharma, and Eli Lilly; and has received clinical trial funding 
from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte, InflaRX, Janssen-Cilag, Menlo Therapeutica, Merck, Novartis, 
Pfizer, Regeneron, Trevi, and UCB. LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, 
Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte, Kamedis, LEO Pharma, L’oreal, Menlo, Novartis, Ortho Dermatologics, Pfizer, 
Regeneron, Sanofi, Sun Pharma, and Taro. DT has served as an investigator for AbbVie, Avillion, Amgen, Arcutis, Astellas, 
Astion, Boehringer Ingelheim, Celgene, Dermira, DS BioPharma, Dow Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche 
Ltd, Galderma, GlaxoSmithKline, Incyte, Isotechnika, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and UCB 
Biopharma. MEK, MEV, and KS are employees and shareholders of Incyte Corporation. ELS is an investigator for AbbVie, 
Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron, and is a consultant with honorarium 
for AbbVie, Eli Lilly, Forte Bio, Galderma, Incyte, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi 
Genzyme, and Valeant.

Acknowledgments
Support for this study was provided by Incyte Corporation. Medical writing assistance was provided by Mayur Kapadia, MD, 
an employee of ICON plc (North Wales, PA, USA), and was funded by Incyte Corporation.

References
1. Wei W, et al. J Dermatol. 2018;45(2):150-157. 2. Silverberg JI, et al. Ann Allergy Asthma Immunol.  
2018;121(3):340-347. 3. Bao L, et al. JAKSTAT. 2013;2(3):e24137. 4. Oetjen LK, et al. Cell. 2017; 
171(1):217-228. 5. Quintas-Cardama A, et al. Blood. 2010;115(15):3109-3117. 6. Kim BS, et al.  
J Allergy Clin Immunol. 2020;145(2):572-582.

Efficacy and Safety of Ruxolitinib Cream for the Treatment of 
Atopic Dermatitis: Results From Two Phase 3, Randomized, 
Double-Blind Studies

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