BACKGROUND

• Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate AD
1

• The safety and efficacy of crisaborole was previously established in 2 identically designed, multicenter, randomized, double-blind, vehicle-
controlled Phase 3 trials (AD-301: NCT02118766; AD-302: NCT02118792)2

• Within these trials, pruritus severity was measured using the Severity of Pruritus Scale (SPS), a 4-point rating scale ranging from  
 (none: no itching) to 3 (severe: bothersome itching/scratching which disturbs sleep) adapted from the Atopic Dermatitis Severity Index3  
to quantify itch over a 24-hour recall period (Table 1)

• In the prespecified analysis, SPS data were analyzed using each SPS observation as a single measurement2

• Subsequent validation analysis has determined that the mean of at least 2 SPS observations is necessary to provide a reliable measure of 
pruritus severity

Table 1. Severity of Pruritus Scale (SPS) 

Instructions: Please think about your itching (or your child’s itching if you are completing for your child)  
over the past 24 hours and choose the category that best describes it.

Score Grade Definition

0 None No itching

1 Mild Occasional, slight itching/scratching

2 Moderate Constant or intermittent itching/scratching which is not disturbing sleep

3 Severe Bothersome itching/scratching which is disturbing sleep

OBJECTIVES
• To conduct an extended analysis of the SPS data from the pivotal Phase 3 trials to assess the efficacy of crisaborole for treatment of AD-

associated pruritus using the mean of at least 2 SPS observations to provide a reliable measure of pruritus 

METHODS
Data Source

• Data were sourced from 2 identically designed, multicenter, vehicle-controlled, double-blind, Phase 3 crisaborole trials (AD-301: NCT02118766; 
AD-302: NCT02118792)2 

 – Eligible patients were ≥2 years of age, with a clinical diagnosis of AD with ≥5% treatable body surface area involvement and a baseline 
Investigator’s Static Global Assessment (ISGA) score of mild (2) or moderate (3) (the ISGA is a 5-point rating scale measuring overall 
disease severity from clear [0] to severe [4])

 – Patients were randomly assigned 2:1 to receive crisaborole or vehicle and instructed to apply the study drug to each lesion twice daily 
for 28 days

 – Pruritus severity was recorded twice daily using the SPS via electronic diary from baseline/day 1 through day 29

Analysis

• Improvement in pruritus was indicated by an SPS score ≤1, with at least a 1-grade improvement from baseline
• A minimum of 2 SPS observations were averaged for each analysis to meet the test-retest reliability threshold of acceptability (intraclass 

correlation coefficient ≥0.70)
 – Baseline for all analyses was the mean of ≥2 SPS measurements on day 1 

Time to Improvement in Pruritus

• Based on daily SPS values, calculated as the mean of ≥2 SPS measurements on that day

Proportion of Patients Who Experienced Improvement in Pruritus

• Assessed at each weekly study visit and calculated using the mean of all available postbaseline SPS scores for the patient during the 
corresponding preceding week (generally up to 14 measurements)

Pruritus Score by Week

• Weekly SPS scores were calculated as the mean of all available postbaseline SPS scores for the patient during the corresponding 
preceding week (up to 14 measurements)

• Scores were analyzed using a repeated-measures longitudinal model with fixed effects for treatment, visit, treatment-by-visit interaction, 
and baseline value

• The previously estimated clinically important difference (CID) of 0.20 was used as a threshold to assess the clinical meaningfulness of the 
treatment effect

Proportion of Responders by Week

• Per the pruritus score by week analysis, weekly SPS scores were calculated as the mean of all available postbaseline SPS scores for the 
patient during the preceding corresponding week (up to 14 measurements) 

• Responders were defined by a previously estimated clinically important response (CIR) of ≥0.19-point reduction in severity of pruritus from 
baseline

The Effect of Crisaborole Ointment, 2%, on Pruritus in Patients With  

Atopic Dermatitis (AD): An Extended Analysis

Gil Yosipovitch,1 Eric Simpson,2 Huaming Tan,3 Robert A. Gerber,3 Thomas Luger,4 Sonja Ständer,4 Wynnis Tom,5 Joseph C. Cappelleri,3 Andrew G. Bushmakin,3 William C. Ports,3 Anna M. Tallman6

1University of Miami, Miller School of Medicine, Miami, FL, USA; 2Oregon Health and Science University, Portland, OR, USA; 3Pfizer Inc., Groton, CT, USA; 4University Hospital Münster, Münster, Germany; 5Rady Children’s Hospital-San Diego, San Diego, CA, USA; 6ICON plc, Gaithersburg, MD, USA; 6Pfizer Inc., New York, NY, USA

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

RESULTS
• The intent-to-treat population included 759 patients in AD-301 (503 crisaborole; 256 vehicle) and 763 patients in AD-302 (513 crisaborole; 

250 vehicle)2 

• The mean baseline SPS scores (standard deviation [SD]) were 1.83 (0.79) for crisaborole-treated patients and 1.75 (0.83) for  
vehicle-treated patients in AD-301 and were 1.81 (0.77) for crisaborole-treated patients and 1.79 (0.72) for vehicle-treated patients in AD-302

 Time to Improvement in Pruritus

• Median time to improvement in pruritus was significantly less for crisaborole-treated patients than for vehicle-treated patients in both trials 
(Figure 1)

 – AD-301: 5.0 days (95% CI, 4.0-6.0 days) for crisaborole-treated patients compared with 10.0 days (95% CI, 7.0-18.0 days) for  
vehicle-treated patients (P = 0.0003) (Figure 1A)

 – AD-302: 6.0 days (95% CI, 5.0-7.0 days) for crisaborole-treated patients compared with 9.0 days (95% CI, 7.0-13.0 days) for  
vehicle-treated patients (P = 0.0087) (Figure 1B)

Figure 1. Kaplan-Meier plot of time to improvement in pruritus. (A) AD-301 and (B) AD-302.

0

20

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10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 122 23 24 25 26 27 28 29 30 31 32

Days After Dosing

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10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 122 23 24 25 26 27 28 29 30 31 32

Days After Dosing

Crisaborole, 2%

N = 381

5.0

4.0-6.0

0.0003

Median, days

95% CI

P value for log-rank test

Vehicle

N = 190

10.0

7.0-18.0

—

Crisaborole, 2%

N = 383

6.0

5.0-7.0

0.0087

Median, days

95% CI

P value for log-rank test

Vehicle

N = 181

9.0

7.0-13.0

—

A

B
Crisaborole

Vehicle 

Crisaborole

Vehicle 

BID, twice daily; SPS, Severity of Pruritus Scale.
Improvement in pruritus was indicated by an SPS score ≤1, with at least a 1-grade improvement from baseline. Baseline was the mean of at least 2 SPS assessments on day 1. Patients with 
fewer than 2 SPS assessments on day 1 were considered to have missing data. SPS daily values were calculated as the mean of 2 or more assessments on that day. If fewer than 2 
assessments were available, SPS was considered missing. Analysed using Kaplan-Meier methods and the log-rank test. 

Proportion of Patients Who Experienced Improvement in Pruritus

• A significantly greater proportion of crisaborole-treated patients exhibited improvement in pruritus at each weekly time point than  
vehicle-treated patients in both trials (Figure 2)

 – AD-301 week 4: 37% (95% CI, 32%-42%) of crisaborole-treated patients compared with 21% (95% CI, 15%-27%) of vehicle-treated 
patients (P < 0.0001) (Figure 2A)

 – AD-302 week 4: 34% (95% CI, 30%-39%) of crisaborole-treated patients compared with 21% (95% CI, 14%-27%) of vehicle-treated 
patients (P = 0.0006) (Figure 2B)

Figure 2. Proportion of patients who experienced improvement in pruritus. (A) AD-301 and (B) AD-302.

21%

32%
35%

37%

10%

17%
19%

21%

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Crisaborole

Vehicle 

P < 0.0001 P = 0.0003 P < 0.0001 P < 0.0001 

Number of Patients
Crisaborole

Vehicle

80

19

122

30

129

33

135

36

16%

27%
19%

34%

9%

14%
16%

21%

0

10

20

30

40

50
B

Week 1 Week 2 Week 3 Week 4

Crisaborole

Vehicle 

P < 0.0002 P = 0.0120 P < 0.0004 P < 0.0006 

Number of Patients
Crisaborole

Vehicle

61

16

103

25

106

27

125

34

SPS, Severity of Pruritus Scale.
Improvement in pruritus was indicated by an SPS score ≤1, with at least a 1-grade improvement from baseline. Baseline was the mean of at least 2 SPS assessments on day 1. Patients with fewer 
than 2 SPS assessments on day 1 were considered to have missing data. Weekly SPS scores for each subject were calculated as the mean of all available postbaseline SPS scores for the subject 
during the corresponding week (generally up to 14 measurements). Only subjects with a mean baseline value and a postbaseline assessment were included. Error bars denote standard error. 

Pruritus Score by Week

• Crisaborole-treated patients exhibited significantly lower mean pruritus scores than vehicle-treated patients at each weekly time point in both 
trials (Figure 3)

• The least-squares mean difference between pruritus scores for crisaborole-treated and vehicle-treated patients was ≥0.20 at all time points 
in both trials, which exceeded the CID previously identified (Figure 3)

Figure 3. Least-squares mean difference in pruritus score. (A) AD-301 and (B) AD-302.

CRISABOROLE VEHICLE DIFFERENCE FROM VEHICLE 

n LS Mean SE n LS Mean SE Difference, 95% CI P Value

Week 1 381 1.19 0.03 180 1.32 0.04 –0.20 (–0.11, –0.30) <0.0001

Week 2 376 1.09 0.03 175 1.31 0.05 –0.22 (–0.11, –0.33) <0.0001

Week 3 368 1.09 0.03 170 1.37 0.05 –0.28 (–0.16, –0.40) <0.0001

Week 4 363 1.08 0.04 165 1.35 0.05 –0.26 (–0.13, –0.38) <0.0001

LS Mean Difference, 
95% CI

Favors Crisaborole

–0.50 –0.25 0.00

CRISABOROLE VEHICLE DIFFERENCE FROM VEHICLE 

n LS Mean SE n LS Mean SE Difference, 95% CI P Value

Week 1 381 1.16 0.03 188 1.42 0.04 –0.26 (–0.16, –0.36) <0.0001

Week 2 377 1.03 0.03 181 1.36 0.05 –0.33 (–0.22, –0.45) <0.0001

Week 3 373 1.01 0.04 175 1.32 0.05 –0.31 (–0.19, –0.44) <0.0001

Week 4 363 0.97 0.04 170 1.28 0.05 –0.31 (–0.18, –0.44) <0.0001

LS Mean Difference, 
95% CI

CID

Favors Crisaborole

–0.50 –0.25 0.00

1

2

3

4

A

B

CID

CID, clinically important difference; LS, least squares; SE, standard error; SPS, Severity of Pruritus Scale.
The dotted line represents the estimated CID of 0.20. Baseline was the mean of at least 2 SPS assessments on day 1. Subjects with fewer than 2 SPS assessments on day 1 were considered to 
have missing data. Weekly SPS scores for each subject were calculated as the mean of all available postbaseline SPS scores for the subject during the corresponding week (generally up to 14 
measurements). Only subjects with nonmissing baseline scores were included. All statistics were derived from a repeated-measures model with fixed effects for treatment, visit, treatment-by-visit 
interaction, and baseline value. Error bars denote standard error of least-squares mean. 

Proportion of Responders by Week

• A significantly greater proportion of crisaborole-treated patients experienced CIR (defined as ≥0.19-point reduction in severity of pruritus 
from baseline) than vehicle-treated patients at each time point in AD-301 and at weeks 2 and 3 in AD-302 (Figure 4)

Figure 4. Proportion of patients experiencing clinically important response. (A) AD-301 and (B) AD-302.

72%
75% 74% 75%

53%
56% 57% 57%

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Number of Patients
Crisaborole

Vehicle

276

99

284

101

276

99

271

97

73%
76% 74% 72%

66% 64% 63% 64%

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P = 0.0045 P = 0.0898 P = 0.0117 P = 0.0828 

Number of Patients
Crisaborole

Vehicle

227

118

286

112

272

107

261

106

A
Crisaborole

Vehicle 

B
Crisaborole

Vehicle 

SPS, Severity of Pruritus Scale.
Responders were defined by a ≥0.19-point reduction in severity of pruritus from baseline. Baseline was the mean of at least 2 SPS assessments on day 1. Weekly SPS scores for each subject 
were calculated as the mean of all available postbaseline SPS scores for the subject during the corresponding week (generally up to 14 measurements). Only subjects with an average baseline 
and postbaseline assessments were included. 

CONCLUSIONS
• The results of this extended analysis confirm that crisaborole is effective in treating AD-associated pruritus

 – Patients treated with crisaborole experienced improvement in pruritus earlier than vehicle-treated patients 
 – Crisaborole-treated patients exhibited significantly lower pruritus scores than vehicle-treated patients, with a difference  
that was considered clinically meaningful 

 – A greater proportion of crisaborole-treated patients experienced improvement in severity of pruritus and CIR than  
vehicle-treated patients

REFERENCES
1. Eucrisa (crisaborole) ointment, 2%, for topical use [prescribing information]. Palo Alto, CA: Anacor Pharmaceuticals, Inc.; 2016.
2. Paller AS et al. J Amer Acad of Derm. 2016;75(3):494-503.e6.
3. Van Leent EJ et al. Arch Dermatol. 1998;134(7):805-809.

ACKNOWLEDGMENTS
Editorial/medical writing support under the guidance of the authors was provided by Jemimah Walker, PhD, and Corey Mandel, PhD, at 
ApotheCom, San Francisco, CA, USA, and was funded by Pfizer Inc., New York, NY, USA, in accordance with Good Publication Practice 
(GPP3) guidelines (Ann Intern Med. 2015;163:461-464).


	FC17PosterPfizerYosipovitchEffectCrisaborole.pdf