Andrew Blauvelt, MD, MBA,1 Lawrence F. Eichenfield, MD,2 Michael E. Kuligowski, MD, PhD, MBA,3 May E. Venturanza, MD,3 Kang Sun, PhD,3 
Jonathan I. Silverberg, MD, PhD, MPH4

Introduction
● Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, dryness, 

and redness1

● Treatments for AD include topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and 
systemic immunomodulatory agents1

● Some topical treatments may be insufficient because of inadequate efficacy, delayed onset
of efficacy, duration-of-use limitations, anatomic use restrictions, poor tolerability, and/or 
adverse reactions1,2

– TCS are associated with decreased skin thickness and elasticity (eg, striae); they are also not 
recommended for long-term application or use in sensitive areas

– TCI are associated with local reactions, such as stinging and burning

● Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 
1 and JAK23

● In two phase 3 randomized studies of identical design (TRuE-AD1 [NCT03745638] and
TRuE-AD2 [NCT03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with 
antipruritic action vs vehicle and was well tolerated in patients with AD3 

Objective
● To evaluate the long-term safety and disease control of ruxolitinib cream based on types of

previous medication using pooled data from two phase 3 trials in patients with AD

Methods

Study Design and Patients
● Eligible patients were aged ≥12 years with AD for ≥2 years and had an Investigator’s Global

Assessment (IGA) score of 2 or 3 and 3%–20% affected body surface area (BSA), 
excluding scalp 

● 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 or medical condition that could interfere with study conduct, interpretation of
data, or patients’ well-being

– The washout period for prior therapies was 1 week for topical AD treatments, 4 weeks for
systemic corticosteroids or other immunomodulating agents, and 12 weeks or 5 half-lives
for biologics

● TRuE-AD1 and TRuE-AD2 had identical study designs (Figure 1)

– In both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens
(0.75% twice daily [BID], 1.5% BID) or vehicle cream BID for 8 weeks of double-blinded
continuous treatment (vehicle-controlled [VC] period); patients were instructed to continue treating
lesions even if they improved

– Patients on ruxolitinib cream subsequently continued treatment for 44 weeks (long-term safety
[LTS] period); patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either
ruxolitinib cream regimen
■ During the LTS period, patients were instructed to treat skin areas with active AD only and

stop treatment 3 days after clearance of lesions; patients were to restart treatment with
ruxolitinib cream at the first sign of recurrence

Figure 1. Study Design

• Continuous treatment for 8 weeks
• Rescue treatment not permitted

• Treat as needed for 44 weeks
• Stop treatment 3 days after lesion clearance
• Rescue treatment not permitted

Vehicle-controlled period Long-term safety period

Patients initially
randomized to RUX

remain on their regimen 

Patients on vehicle
rerandomized 1:1 to
0.75% RUX BID or

1.5% RUX BID

Patients 
Randomized

2:2:1
RUX†

Visits every 4 weeks

Week 52Day 1 Week 8

Recurrence of 
lesions 

Clearance of 
lesions 

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

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

Vehicle BID
(n=~120 in each study)

AD, atopic dermatitis; BID, twice daily; BSA, body surface area; RUX, ruxolitinib cream. 
†  Patients self-evaluated recurrence of lesions between study visits and treated lesions with active AD (≤20% BSA). If lesions cleared 

between study visits, patients stopped treatment 3 days after lesion disappearance. If new lesions were extensive or appeared in new 
areas, patients contacted the investigator to determine if an unscheduled additional visit was needed.

1Oregon Medical Research Center, Portland, OR, USA; 
2Departments of Dermatology and Pediatrics, University of 
California San Diego, San Diego, CA, USA; 3Incyte Corporation, 
Wilmington, DE, USA; 4George Washington University, 
Washington, DC, USA 

Assessments
● Disease control was assessed by the proportion of patients who achieved no or minimal skin

lesions (IGA score of 0 or 1 [clear or almost clear skin]) and mean percentage of BSA affected by
AD at each visit (every 4 weeks) during the LTS period

● Safety and tolerability assessments included the frequency of reported treatment-emergent
adverse events (TEAEs), treatment-related adverse events, and adverse events (AEs) leading to
treatment discontinuation

Statistical Analysis
● All analyses were conducted using the pooled data from both studies

– The disease control analysis included patients who remained on their initial ruxolitinib cream
strength regimen from the VC period through the LTS period; data are reported as observed

– The safety analysis included patients who received ruxolitinib cream in any period (VC or LTS)
● Data were summarized using descriptive statistics

Results

Patients
● A total of 1249 patients (median age, 32 years) were randomized in the VC period, and 1072

continued in the LTS period (vehicle to ruxolitinib cream, n=200 [101 to 0.75% and 99 to 1.5%];
0.75% ruxolitinib cream, n=426; 1.5% ruxolitinib cream, n=446)

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

Table 1. Patient Demographics and Baseline Clinical Characteristics

Characteristic
Vehicle 
(n=250)

0.75% RUX 
(n=500)

1.5% RUX 
(n=499)

Total
(N=1249)

Age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85)

Female, n (%) 159 (63.6)   304 (60.8)   308 (61.7)   771 (61.7)

Race, n (%)

White 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7)

Black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4)

Asian 10 (4.0) 16 (3.2) 20 (4.0) 46 (3.7)

Other 9 (3.6) 21 (4.2) 11 (2.2) 41 (3.3)

Region, n (%)

North America 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5)

Europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5)

BSA, mean (SD), % 9.6 (5.5) 10.0 (5.3) 9.6 (5.3) 9.8 (5.4)

EASI, mean (SD) 7.8 (4.8) 8.1 (4.9) 7.8 (4.8) 8.0 (4.8)

IGA, n (%)

2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0)

3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0)

Itch NRS score, mean (SD) 5.1 (2.4) 5.2 (2.4) 5.1 (2.5) 5.1 (2.4)

≥4, n (%) 159 (63.6) 324 (64.8) 315 (63.1) 798 (63.9)

Duration of disease, median 
(range), y

16.5  
(0.8–79.1)

15.1  
(0.1–68.8)

16.1  
(0–69.2)

15.8  
(0–79.1)

Facial involvement, n (%)* 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8)

Number of flares in last 12 mo, 
mean (SD)* 

7.3 (25.7) 5.2 (6.7) 6.0 (17.6) 5.9 (16.5)

BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, numerical rating scale; RUX, 
ruxolitinib cream.  
* Patient reported.

Disease Control
● At each visit in the LTS, most patients in the 0.75% or 1.5% ruxolitinib cream groups had an

IGA score of 0/1 (clear or almost clear), regardless of the type of previous medication (Figure 2)
● Regardless of type of previous medication, mean affected BSA was low (generally <3%) during

the LTS among patients who applied 0.75% or 1.5% ruxolitinib cream (Figure 3)

Figure 2. Patients Achieving IGA 0/1 Stratified by the Type of Previous Medication 
Among Patients Who Applied (A) 0.75% or (B) 1.5% Ruxolitinib Cream

n
n

93
n 321

84
n
n

82
30

89
311

82
81
28

88
301

81
79
28

78
279

72
72
25

78
270

71
70
25

72
254

65
62
21

71
250

65
60
22

78
257

72
65
20

79
265

72
67
23

80
262

73
70
23

83
266

76
73
24

A) 0.75% Ruxolitinib Cream

40

50

60

70

0

10

20

30

80

90

12 16 20 24 28 32 36 40 44 48 52

Pa
tie

nt
s 

W
ith

 C
le

ar
 o

r A
lm

os
t C

le
ar

 S
ki

n 
(IG

A 
of

 0
 o

r 1
), 

%
 

Time, wk

77.1

75.9
76.3

68.5
62.5

TCS TCI TCS+TCI Systemic Phototherapy

n
n

92
n 325

82
n
n

83
38

92
318

82
81
38

91
312

81
80
38

87
297

77
74
36

77
281

68
66
31

68
271

59
66
28

75
276

66
69
33

74
268

65
66
34

82
280

73
72
35

82
262

74
67
33

86
276

77
71
33

B) 1.5% Ruxolitinib Cream

40

50

60

70

0

10

20

30

80

90

12 16 20 24 28 32 36 40 44 48 52

Pa
tie

nt
s 

W
ith

 C
le

ar
 o

r A
lm

os
t C

le
ar

 S
ki

n 
(IG

A 
of

 0
 o

r 1
), 

%
 

Time, wk

TCS TCI TCS+TCI Systemic Phototherapy

79.0

77.9
76.7

66.7

78.9

IGA, Investigator’s Global Assessment; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid.

Figure 3. Mean Affected BSA Stratified by the Type of Previous Medication Among 
Patients Who Applied (A) 0.75% or (B) 1.5% Ruxolitinib Cream

n
n

93
n 321

84
n
n

82
30

89
311

82
81
28

88
301

81
79
28

80
281

74
73
26

78
271

71
70
25

72
255

65
62
21

72
251

66
60
22

78
257

72
65
20

79
266

72
68
23

80
263

73
71
24

83
266

76
73
24

A) 0.75% Ruxolitinib Cream

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

12 16 20 24 28 32 36 40 44 48 52

M
ea

n 
To

ta
l A

ffe
ct

ed
 B

SA
, %

Time, wk

1.8

2.5
2.4

2.7
2.6

n
n

92
n 325

82
n
n

83
38

92
318

82
81
38

91
312

81
80
38

87
297

77
74
36

77
281

68
67
32

68
271

59
66
28

75
276

66
69
33

74
269

65
66
34

82
280

73
72
35

82
263

74
67
33

86
277

77
71
34

B) 1.5% Ruxolitinib Cream

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

12 16 20 24 28 32 36 40 44 48 52

M
ea

n 
To

ta
l A

ffe
ct

ed
 B

SA
, %

Time, wk

TCS TCI TCS+TCI Systemic Phototherapy

TCS TCI TCS+TCI Systemic Phototherapy

1.3

1.9
2.0

1.9
1.7

BSA, body surface area; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid.

Safety
● Ruxolitinib cream was well tolerated across all subgroups of previous treatment; the frequency

of application site reactions was low (Table 2)

● In the overall population, the most common TEAEs through Week 52 were upper respiratory

tract infection, nasopharyngitis, and headache

– No AEs suggestive of a relationship to systemic exposure were observed

Table 2. Adverse Events According to the Type of Previous Medication Among 
Patients Who Applied Ruxolitinib Cream in the Phase 3 Studies (VC or LTS Periods)

Parameter TCS TCI TCS+TCI
Systemic 
Therapies Phototherapy

Patients, n
0.75% RUX 461 134 121 106 42
1.5% RUX 461 121 109 110 48

TEAEs, n (%)
0.75% RUX 286 (62.0) 97 (72.4) 87 (71.9) 80 (75.5) 30 (71.4)
1.5% RUX 270 (58.6) 85 (70.2) 80 (73.4) 76 (69.1) 38 (79.2)

Application site reactions, n (%)
0.75% RUX 15 (3.3) 5 (3.7) 4 (3.3) 3 (2.8) 2 (4.8)
1.5% RUX 9 (2.0) 4 (3.3) 4 (3.7) 4 (3.6) 2 (4.2)

TRAEs, n (%)
0.75% RUX 36 (7.8) 18 (13.4) 15 (12.4) 13 (12.3) 8 (19.0)
1.5% RUX 35 (7.6) 19 (15.7) 19 (17.4) 15 (13.6) 7 (14.6)

TEAEs resulting in 
discontinuation, n (%)

0.75% RUX 8 (1.7) 1 (0.7) 1 (0.8) 3 (2.8) 1 (2.4)
1.5% RUX 4 (0.9) 1 (0.8) 1 (0.9) 1 (0.9) 0

Serious TEAEs, n (%)
0.75% RUX 15 (3.3) 3 (2.2) 3 (2.5) 6 (5.7) 1 (2.4)
1.5% RUX 10 (2.2) 2 (1.7) 2 (1.8) 1 (0.9) 1 (2.1)

LTS, long-term safety; RUX, ruxolitinib cream; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid;  TEAE, treatment-emergent 
adverse event; TRAE, treatment-related adverse event; VC, vehicle controlled.

Conclusions
● Ruxolitinib cream, used as maintenance therapy,

demonstrated effective long-term disease control,
regardless of the type of previous therapy

● Ruxolitinib cream was well tolerated over a period up to
52 weeks, regardless of the type of previous therapy

Disclosures
AB has served as a scientific advisor and/or clinical study investigator for AbbVie, Abcentra, Aligos, 
Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, 
Eli Lilly and Company, Evommune, Forte, Galderma, Incyte Corporation, Janssen, Landos, LEO Pharma, 
Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma. LFE has served as 
an investigator, consultant, speaker, or data safety monitoring board member for AbbVie, Almirall, Arcutis, 
Asana, Dermavant, Eli Lilly, Forte Biosciences, Galderma, Ichnos/Glenmark, Incyte Corporation, Janssen, 
LEO Pharma, Novartis, Ortho Dermatologics, Otsuka, Pfizer, Regeneron, and Sanofi Genzyme. MEV and  
KS are employees and shareholders of Incyte Corporation. MEK was an employee and shareholder of  
Incyte Corporation at the time of development of the original presentation. JIS has received honoraria 
for advisory board, speaker, and consultant services from AbbVie, Asana, Bluefin, Boehringer Ingelheim, 
Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte Corporation, Kiniksa, 
LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron, and Sanofi and research grants for 
investigator services from Galderma and GlaxoSmithKline.

Acknowledgments
The authors thank the patients, investigators, and investigational sites whose participation made the 
study possible. Support for this study was provided by Incyte Corporation (Wilmington, DE, USA). Writing 
assistance was provided by Joshua Solomon, PhD, an employee of ICON (North Wales, PA, USA),  
and was funded by Incyte Corporation.

References
1. Langan SM, et al. Lancet. 2020;396(10247):345-360. 2. Eichenfield LF, et al.
J Am Acad Dermatol. 2014;71(1):116-132. 3. Papp K, et al. J Am Acad Dermatol.
2021;85(4):863-872.

Long-Term Safety and Disease Control With Ruxolitinib Cream Among Patients 
With Atopic Dermatitis Based on Previous Medication History: Pooled Results  
From Two Phase 3 Studies

Presented at the

Fall Clinical Dermatology Conference
Las Vegas, NV • October 21–24, 2021 

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