S2010516 FCPANP 2020 Simpson_without QR code.indd


Presented at the 5th Fall Clinical Dermatology Conference for PAs & NPs (FCPANP).

BACKGROUND
• Atopic dermatitis (AD) is a chronic inflammatory skin condition 

characterized by pruritus and disruption of skin-barrier function, 
predominantly driven by type 2 inflammation1

• In a majority of patients with moderate-to-severe AD, circulating 
C-C motif chemokine ligand 17 (CCL17, also known as thymus and 
activation-regulated chemokine [TARC]) and total IgE concentrations 
are elevated and correlate with disease severity2–4 

• Serum TARC, IgE, and lactate dehydrogenase (LDH) have been 
suggested as biomarkers for monitoring AD disease activity and 
treatment response4

• Dupilumab is a fully human monoclonal antibody5,6 that blocks the 
shared receptor component for interleukin (IL)-4 and IL-13, thus 
inhibiting signaling of both IL-4 and IL-13, which are key drivers of 
type 2 inflammation7

Dupilumab Decreases Blood Biomarkers in Adolescents With Moderate-to-Severe Atopic  
Dermatitis: Data From a Phase 3 Trial (LIBERTY AD ADOL)

Eric L. Simpson1, Hiroyuki Fujita2, Kazuhiko Arima2, Jennifer Hamilton3, Yufang Lu3, Ana B. Rossi4, Ashish Bansal3 
1Oregon Health and Science University, Portland, OR, USA; 2Sanofi KK, Tokyo, Japan; 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 4Sanofi Genzyme, Cambridge, MA, USA

Baseline demographics and disease characteristics
• Demographics and baseline characteristics were similar across 

treatment groups and showed considerable disease burden at 
baseline; > 90% of patients had ≥ 1 comorbid type 2 inflammatory 
disease including allergic rhinitis, asthma, or food allergy  
(Table 1)

• Baseline blood levels of TARC, total IgE, LDH, and allergen-specific IgE 
are shown in Table 2

METHODS
Study design
• LIBERTY AD ADOL (NCT03054428) study design has been published 

previously8 and is summarized in Figure 1

Screening
Age ≥ 12 to < 18 years
•  Moderate-to-severe AD
•  AD inadequately controlled
    by topical therapies
•  Scores on IGA ≥ 3, EASI ≥ 16, 
    Peak Pruritus NRS ≥ 4;
    BSA involvement ≥ 10%
Washout
•  Prior medication
Stratification
•  Body weight
    (< 60 kg or ≥ 60 kg)
•  IGA score (3 or 4)

Treatment period
(16 weeks)

Follow-up period
(12 weeks)Loading dose on Day 1a 

Day –35 to Day –1 Baseline Week 28Week 16

Post-treatment options
•  Open-label extension
•  Safety follow-up
    through Week 28

Placebo (n = 85) 

Dupilumab 300 mg SC q4w (n = 84)

Dupilumab 200 or 300b mg SC
q2w (n = 82)

R
1:1:1

Figure 1. Study design.

aFor q2w, patients with body weight < 60 kg at baseline received a loading dose of 400 mg on Day 1, 
while patients with body weight ≥ 60 kg received a loading dose of 600 mg. All patients in every 4 weeks 
(q4w), regardless of weight, received a 600 mg loading dose. bPatients with body weight < 60 kg received 
200 mg of the study drug; patients with body weight ≥ 60 kg received 300 mg. BSA, body surface area; 
EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, Numerical Rating 
Scale; R, randomization.

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Placebo Dupilumab 300 mg q4w Dupilumab 200/300 mg q2w

Figure 4. (A) Median change and (B) median percent change from 
baseline in LDH concentration over time.a

aLOCF method for the last post-baseline available observed status prior to rescue treatment to visit Week 
16 was carried forward to impute missing data.
***Nominal P < 0.0001 vs placebo at Weeks 4, 8, and 16.

Placebo Dupilumab 300 mg q4w Dupilumab 200/300 mg q2w

–8,000

–7,000

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Figure 2. (A) Median change and (B) median percent change from 
baseline in TARC concentration over time.a

aLast observation carried forward (LOCF) method for the last post-baseline available observed status prior 
to rescue treatment to visit Week 16 was carried forward to impute missing data.
***Nominal P < 0.0001 vs placebo at Weeks 2, 4, 8, 12, and 16.

Placebo Dupilumab 300 mg q4w Dupilumab 200/300 mg q2w

–6,000

–5,000

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Figure 3. (A) Median change and (B) median percent change from 
baseline in total IgE concentration over time.a

aLOCF method for the last post-baseline available observed status prior to rescue treatment to visit Week 
16 was carried forward to impute missing data.
***Nominal P < 0.0001 vs placebo at Weeks 4, 8, 12, and 16.

Table 1. Baseline demographics and disease characteristics.a

  Range
Placebo
(n = 85)

Dupilumab
300 mg q4w

(n = 84)

Dupilumab
200/300 mg q2w

(n = 82)

Age, mean (SD), years 12–17 14.5 (1.8) 14.4 (1.6) 14.5 (1.7)

Male, n (%) – 53 (62.4) 52 (61.9) 43 (52.4)

Weight, mean (SD), kg – 64.4 (21.5) 65.8 (20.1) 65.6 (24.5)

Duration of AD, mean (SD), 
years

– 12.3 (3.4) 11.9 (3.2) 12.5 (3.0)

Patients with IGA score,  
n (%)

0–4

 3 – 39 (45.9) 38 (45.2) 39 (47.6)

 4 – 46 (54.1) 46 (54.8) 43 (52.4)

EASI score, mean (SD) 0–72 35.5 (14.0) 35.8 (14.8) 35.3 (13.8)

Peak pruritus NRS score, 
mean (SD)

0–10 7.7 (1.6) 7.5 (1.8) 7.5 (1.5)

Percent BSA involvement, 
mean (SD)

0–100 56.4 (24.1) 56.9 (23.5) 56.0 (21.4)

SCORAD score, mean (SD) 0–103 70.4 (13.3) 69.8 (14.1) 70.6 (13.9)

CDLQI, mean (SD) 0–30 13.1 (6.7) 14.8 (7.4) 13.0 (6.2)

POEM score, mean (SD) 0–28 21.1 (5.4) 21.1 (5.5) 21.0 (5.0)

HADS score, mean (SD) 0–42 11.6 (7.8) 13.3 (8.2) 12.6 (8.0)

Patients with ≥ 1 
concurrent allergic 
condition, n (%)

– 78 (91.8) 73 (88.0) 79 (96.3)

 Allergic rhinitis – 57 (67.1) 48 (57.8) 59 (72.0)

 Asthma – 46 (54.1) 42 (50.6) 46 (56.1)

 Food allergy – 48 (56.5) 52 (62.7) 52 (63.4)

 Allergic conjunctivitis – 16 (18.8) 21 (25.3) 20 (24.4)

 Hives – 22 (25.9) 28 (33.7) 22 (26.8)

 Chronic rhinosinusitis – 7 (8.2) 6 (7.2) 6 (7.3)

 Nasal polyps – 2 (2.4) 1 (1.2) 2 (2.4)

 Eosinophilic esophagitis – 0 0 1 (1.2)

 Other allergies – 62 (72.9) 53 (63.9) 58 (70.7)
aData are n (%) unless otherwise specified.
CDLQI, Children’s Dermatology Life Quality Index; HADS, Hospital Anxiety and Depression Scale; POEM, 
Patient-Oriented Eczema Measure; SCORAD, SCORing Atopic Dermatitis; SD, standard deviation.

Table 2. Median (IQR, Q1–Q3) baseline concentrations of blood 
biomarkers.

Placebo
(n = 85)

Dupilumab
300 mg q4w

(n = 84)

Dupilumab
200/300 mg q2w

(n = 82)

TARC (pg/mL) 
2,160.0  

(1,120.0–6,000.0)
2,095.0  

(1,110.0–5,350.0)
2,940.0  

(974.0–7,320.0)

Total IgE (kU/L)
3,983.0  

(813.0–10,931.0)
3,482.0  

(728.0–10,000.0)
3,739.5  

(1,699.0–9,517.0)

LDH (U/L)
259.0  

(223.0–321.0)
275.5  

(227.0–362.0)
277.0  

(213.0–344.0)

Allergen-specific IgE

  Cat dander-specific IgE (kU/L) 20.7 (1.4–62.3) 27.9 (3.8–72.8) 35.2 (4.7–69.2)

  Cow’s milk-specific IgE (kU/L) 0.6 (0.2–4.9) 0.5 (0.2–1.7) 0.8 (0.2–3.2)

  Egg white-specific IgE (kU/L) 0.4 (0.1–5.6) 0.7 (0.2–4.1) 0.8 (0.2–3.5)

  Peanut-specific IgE (kU/L) 3.4 (0.2–47.9) 3.5 (0.4–38.7) 6.7 (0.5–46.3)

  Dust mite-specific IgE (kU/L) 39.9 (0.5–302.0) 15.1 (1.7–93.3) 27.7 (2.0–211.5)

IQR, interquartile range; Q, quartile.

Table 3. Efficacy outcomes at Week 16.a,b 

Placebo
(n = 85)

Dupilumab
300 mg q4w

(n = 84)

Dupilumab
200/300 mg q2w

(n = 82)

Patients with IGA 0 or 1 2 (2.4) 15 (17.9)c 20 (24.4)d

Patients with EASI-75 7 (8.2) 32 (38.1)d 34 (41.5)d

Proportion of patients with ≥ 3-point 
improvement (reduction) in weekly average 
of daily Peak Pruritus NRS from baselinee

8/85 (9.4) 32/83 (38.6)d 40/82 (48.8)d

Proportion of patients with ≥ 4-point 
improvement (reduction) in weekly average 
of daily Peak Pruritus NRS from baseline

4/84 (4.8) 22/83 (26.5)f 30/82 (36.6)d

Least squares mean percent change from 
baseline in weekly average of daily Peak 
Pruritus NRS (SE)

–19.0 (4.1) –45.5 (3.5)d –47.9 (3.4)d

Percent BSA involvement, mean (SD)g 42.1 (25.4) 23.4 (19.9) 26.4 (25.4)

Least squares mean percent change from 
baseline in  
SCORAD (SE)

–17.6 (3.8) –47.5 (3.2)d –51.6 (3.2)d

Least squares mean change  
from baseline in CDLQI (SE)

–5.1 (0.6) –8.8 (0.5)d –8.5 (0.5)d

Least squares mean change  
from baseline in POEM (SE)

–3.8 (1.0) –9.5 (0.9)d –10.1 (0.8)d

Least squares mean change  
from baseline in total HADS (SE)

–2.5 (0.8) –5.2 (0.7)h –3.8 (0.7)i

aCoprimary outcomes were the proportion of patients with EASI75 and IGA score 0/1 at Week 16.
bData are n (%) unless otherwise specified.
cP = 0.0007 vs placebo. 
dP < 0.0001 vs placebo. 
eAn improvement of ≥ 3 points from baseline in Peak Pruritus NRS score represents a clinically meaningful 
response.9,10
fP = 0.0001. 
gAll observed data values regardless of rescue treatment use. 
hNominal P = 0.0133 vs placebo. 
iNominal P = 0.2203 vs placebo.
SE, standard error.

Table 4. Proportion of patients achieving normalized status in 
blood levels of total IgE and LDH at Week 16.a,b

Placebo
(n = 80)

Dupilumab
300 mg q4w

(n = 77)

Dupilumab
200/300 mg q2w

(n = 77)

Total IgEc 2 (2.5) 7 (9.1)d 3 (3.9)e

LDHf 4 (28.6) 16 (88.9)g 16 (88.9)h

aData are in n (%).
bLOCF method for the last post-baseline available observed status prior to rescue treatment to visit Week 
16 was carried forward to impute missing data.
cNumber of patients evaluated were 80 in placebo group, 77 in dupilumab 300 mg q4w group, and 77 in 
dupilumab 200/300 q2w group.
dP = 0.0681.
eP = 0.6377.
fNumber of patients evaluated were 14 in placebo group, 18 in dupilumab 300 mg q4w group, and 18 in 
dupilumab 200/300 q2w group.
gP = 0.0008. 
hP = 0.0021.
All P values are nominal.

Table 5. (A) Median (IQR, Q1–Q3) change and (B) median  
(IQR, Q1–Q3) percent change in allergen-specific IgE 
concentrations at Week 16.a,b

Allergen
Placebo
(n = 85)

Dupilumab
300 mg q4w (n = 84)

Dupilumab
200/300 mg q2w (n = 82)

A
Cat dander 0.1 (–0.5, 8.9) –4.8 (–26.9, –0.6)*** –12.6 (–29.4, –1.2)***
Cow’s milk 0 (–0.1, 0.2) –0.2 (–0.6, 0)*** –0.3 (–0.9, –0.1)***
Egg white 0 (–0.1, 0.2) –0.3 (–1.0, 0)*** –0.2 (–1.3, 0)***
Peanut 0 (–0.2, 2.9) –0.8 (–4.0, 0)*** –2.1 (–20.8, –0.2)***
Dust mite 0 (–6.1, 1.8) –5 (–49.8, –0.5)*** –10.1 (–94.0, –1.0)***
B
Cat dander 8.9 (–10.66, 35.30) –43.16 (–58.09, –18.75)*** –45.35 (–64.57, –18.40)***
Cow’s milk 0 (–17.39, 34.55) –42.18 (–60.88, –9.52)*** –47.54 (–60.61, –21.92)***
Egg white 0 (–12.18, 20.00) –40.97 (–58.43, 0)*** –41.83 (–59.26, 0)***
Peanut 0.19 (–11.19, 32.07) –38.75 (–57.25, 0)*** –51.81 (–64.30, –23.68)***
Dust mite 0 (–14.77, 26.57) –49.83 (–58.46, –32.25)*** –51.97 (–62.87, –29.40)***
aLOCF method for the last post-baseline available observed status prior to rescue treatment to visit  
Week 16 was carried forward to impute missing data.
bConcentrations of allergen-specific IgE reported as kU/L.
***In (A), nominal P < 0.0001 vs placebo; in (B), P < 0.0001 vs placebo.

Table 6. Adverse events during the study treatment period.a

Placebo
(n = 85)

Dupilumab
300 mg q4w

(n = 83)

Dupilumab
200/300 mg q2w

(n = 82)
Number of patients with
 TEAE 59 (69.4) 53 (63.9) 59 (72.0)
  TEAE leading to permanent 

discontinuation of study drug 
1 (1.2) 0 0

 Serious TEAE 1 (1.2) 0 0
 Death 0 0 0
Most common TEAEsb 
 Dermatitis atopic (PT) 21 (24.7) 15 (18.1) 15 (18.3)
  Skin infections (adjudicated) 17 (20.0) 11 (13.3) 9 (11.0)
  Skin infections excluding herpetic 

skin infections (adjudicated) 
16 (18.8) 8 (9.6) 8 (9.8)

  Upper respiratory tract infection (PT) 15 (17.6) 6 (7.2) 10 (12.2)
 Headache (PT) 9 (10.6) 4 (4.8) 9 (11.0)
 Conjunctivitisc 4 (4.7) 9 (10.8) 8 (9.8)
 Nasopharyngitis (PT) 4 (4.7) 9 (10.8) 3 (3.7)
  Infections and infestations (SOC) 37 (43.5) 38 (45.8) 34 (41.5)
  Injection-site reaction (HLT) 3 (3.5) 5 (6.0) 7 (8.5)
  Herpes viral infections (HLT) 3 (3.5) 4 (4.8) 1 (1.2)
aData are in n (%).
bPTs occurring in ≥ 5% of patients in any treatment group.
cIncludes MedDRA PT: atopic keratoconjunctivitis, conjunctivitis, conjunctivitis allergic, conjunctivitis 
bacterial, and conjunctivitis viral. 
HLT, MedDRA High Level Term; MedDRA, Medical Dictionary for Regulatory Activities; PT, MedDRA Preferred 
Term; SOC, MedDRA System Organ Class. TEAE, treatment-emergent adverse event

References: 1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-51. 2. Kakinuma T, et al. J Allergy Clin Immunol. 2001; 107:535-41. 3. Jahnz-Rozyk K, et al. Allergy. 2005; 60:685-8. 4. Thijs JL, et al. Immunol Allergy Clin North Am. 2017; 37:51-61. 5. Macdonald LE, et al. Proc Natl Acad Sci U S A. 2014;111:5147-52. 6. Murphy AJ, et al. Proc Natl Acad Sci U S A. 2014;111:5153-8. 7. Gandhi NA, et al. Expert Rev Clin Immunol. 2017;13:425-37. 8. Simpson EL, et al. JAMA Dermatol. In press 2019. 9. Yosipovitch G, et al. Br J Dermatol. 2019;181:761-9. 10. Yosipovitch G, et al. Exp Dermatol. 2018;27 Suppl 2:S98. 

Acknowledgments: Data first presented at the 44th Annual Meeting of the Japanese Society for Investigative Dermatology (JSID); Aomori, Japan; November 8–10, 2019.

Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT03054428 (LIBERTY AD ADOL). Medical writing/editorial assistance provided by Raj Menon, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. 

Disclosures: Simpson EL: AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, Regeneron Pharmaceuticals, Inc. – investigator; AbbVie, Boehringer Ingelheim, Dermavant, Eli Lilly, Forte, Incyte, LEO Pharma, Menlo Therapeutics, Pfizer, Pierre Fabre Dermo Cosmétique, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Valeant – consultant honoraria. Fujita H, Arima K: Sanofi – employees, may hold stock and/or stock options in the company. Hamilton J, Lu Y, Bansal A: Regeneron Pharmaceuticals, Inc. employees and shareholders. Rossi A: Sanofi Genzyme – employee, may hold stock and/or stock options in the company.

Blood biomarker levels at Week 16

Safety

RESULTS

OBJECTIVE

• To evaluate blood levels of type 2 inflammatory 
markers in patients from a randomized, 
placebo-controlled, double-blind, phase 3 trial 
of dupilumab in adolescents with moderate-to-
severe AD inadequately controlled by topical 
therapies (LIBERTY AD ADOL)

CONCLUSIONS
• Dupilumab treatment for 16 weeks resulted in a marked reduction in blood levels of multiple type 2 

inflammatory biomarkers (i.e., TARC, total IgE, LDH, and allergen-specific IgE); these effects were 
accompanied by previously reported improvements in AD signs and symptoms10

Efficacy outcomes at Week 16