S2010514 FCPANP 2020 Silverberg_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 disease 

characterized by intense pruritus1

• Patients with AD have an increased risk of anxiety and  
depression,2,3 which often correlates with AD severity

• The Hospital Anxiety and Depression Scale (HADS) is a tool that 
is validated for patients with AD and used to identify patients 
with symptoms of anxiety and depression in non-psychiatric 
settings4

 – HADS contains 2 components, the anxiety (HADS-A)  
and depression (HADS-D) subscales, which make up the total 
score 

• Dupilumab is a fully human5,6 monoclonal antibody that  
blocks the shared receptor component for interleukin (IL)-4  
and IL-13, inhibiting signaling of both IL-4 and IL-13, which 
are key drivers of type 2-mediated inflammation in multiple 
diseases7,8

• In the randomized phase 3 SOLO 1 and 2 trials in adults with 
moderate-to-severe AD, 16-week treatment with dupilumab vs 
placebo significantly improved AD signs, symptoms, and quality 
of life9

• Furthermore, in the randomized phase 3 ADOL trial in adolescents 
with uncontrolled, moderate-to-severe AD, 16-week treatment  
with dupilumab vs placebo significantly improved AD signs, 
symptoms, and quality of life10

Dupilumab Improves Symptoms of Anxiety and Depression in Adults and Adolescents With Moderate-to-Severe 
Atopic Dermatitis: A Post Hoc Analysis of Three Phase 3 Trials (LIBERTY AD SOLO 1 and 2 and ADOL)

Jonathan I. Silverberg1, Weily Soong2, Benjamin Lockshin3, Abhijit Gadkari4, Zhen Chen4, Ashish Bansal4
1George Washington University School of Medicine, Washington DC, USA; 2Alabama Allergy & Asthma Center, Birmingham, AL, USA; 3Georgetown University, Rockville, MD, USA; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

Analysis
• Efficacy was analyzed in all randomized patients (full analysis set), 

and safety outcomes were analyzed in patients who received ≥ 1 
dose of study drug

• Continuous endpoints are reported as least squares (LS) means 
with standard errors (SEs) 

 – Data were treated as missing after rescue medication use or 
early discontinuation 

 – Missing data were imputed using multiple imputation with 
analysis of covariance, with treatment group, disease severity, 
study identifier (SOLO), and region (SOLO) or baseline weight 
(ADOL) as fixed factors

• Categorical endpoints were analyzed using a Cochran–Mantel–
Haenszel test adjusted by the same fixed factors as continuous 
endpoints 

 – Patients were considered non-responders from the time of 
rescue medication use or withdrawal

• Safety was assessed among patients who received ≥ 1 dose of 
any study drug

OBJECTIVE

• To evaluate the effect of dupilumab on anxiety 
and depression in adults and adolescents with 
moderate-to-severe AD

SOLO 1 (NCT02277743) & SOLO 2 (NCT02277769)

N = 1,379
Safety follow-up
through Week 28

1:1:1

R

Placebo

Dupilumab 300 mg q2w

Dupilumab 300 mg qw

ADOL (NCT03054428)

N = 251
Safety follow-up
through Week 28

Baseline

1:1:1

R

Placebo q2w

Dupilumab 200 or 300 mg q2w

Dupilumab 300 mg q4w

Week 16 Week 28

Figure 1. Study designs.

q4w, every 4 weeks; R, randomization.

0
10
20
30
40
50
60
70
80
90

100

Placebo
(N1 = 183)

9.8%P
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w

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-A
 <

 8
 (

%
)

Dupilumab 
300 mg q2w 

(N1 = 196)

(A)

Dupilumab 
300 mg qw
(N1 = 209)

***
40.8%

***
39.2%

(B)

(C) (D)

(E) (F)

0
10
20
30
40
50
60
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100

Placebo
(N1 = 41)

17.1%

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w

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 <

 8
 (

%
)

Dupilumab
200 or 300 mg
q2w (N1 = 47)

Dupilumab
300 mg q4w

(N1 = 42)

*
36.2% 35.7%

0
10
20
30
40
50
60
70
80
90

100

Placebo
(N1 = 139)

14.4%

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 <

 8
 (

%
)

Dupilumab
300 mg q2w 

(N1 = 148)

Dupilumab 
300 mg qw
(N1 = 160)

***
50.7%

***
46.3%

0
10
20
30
40
50
60
70
80
90

100

Placebo
(N1 = 14)

7.1%P
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 <

 8
 (

%
)

Dupilumab
200 or 300 mg 
q2w (N1 = 19)

Dupilumab
300 mg q4w 

(N1 = 23)

*
42.1%

**
65.2%

0
10
20
30
40
50
60
70
80
90

100

Placebo
(N1 = 212)

9.0%

P
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 <

 8
 (

%
)

Dupilumab 
300 mg q2w 

(N1 = 229)

Dupilumab 
300 mg qw 
(N1 = 238)

***
40.2%

***
39.1%

0
10
20
30
40
50
60
70
80
90

100

Placebo
(N1 = 42)

16.7%

P
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 <

 8
 (

%
)

Dupilumab
200 or 300 mg 
q2w (N1 = 49)

Dupilumab 
300 mg q4w 

(N1 = 44)

*
38.8%

*
36.4%

Figure 3. Proportions of patients at Week 16 with: HADS-A < 8a,  
(A) SOLO and (B) ADOL; HADS-D < 8b, (C) SOLO and (D) ADOL; and 
HADS-A < 8c and HADS-D < 8c, (E) SOLO and (F) ADOL.

aAmong patients with HADS-A baseline values ≥ 8. bAmong patients with HADS-D baseline values ≥ 8. cAmong patients 
with baseline values ≥ 8 in ≥ 1 of HADS-A or HADS-D. * P < 0.05; ** P < 0.01; *** P ≤ 0.0001. N1, number of patients 
included in analysis.

0

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Placebo
(N1 = 108)

15.7%

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w
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 <
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1

Dupilumab 
300 mg q2w 

(N1 = 97)

(A)

Dupilumab 
300 mg qw
(N1 = 97)

***
56.7%

***
44.3%

(B)

0

10

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40

50

60

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100

Placebo
(N1 = 17)

23.5%

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w
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-A

 <
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1

Dupilumab 
200 or 300 mg 
q2w (N1 = 24)

Dupilumab 
300 mg q4w 

(N1 = 25)

37.5%

48.0%

(C)

0

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Placebo
(N1 = 71)

15.5%

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w
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 <
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1

Dupilumab 
300 mg q2w 

(N1 = 61)

Dupilumab
300 mg qw
(N1 = 75)

***
62.3%

**
45.3%

(D)

0

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Placebo
(N1 = 6)

33.3%

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 <
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1

Dupilumab 
200 or 300 mg q2w 

(N1 = 8)

Dupilumab
300 mg q4w 

(N1 = 10)

37.5%

70.0%

(E) (F)

0

10

20

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40

50

60

70

80

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100

Placebo
(N1 = 133)

14.3%P
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 <

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1

Dupilumab
300 mg q2w 

(N1 = 120)

Dupilumab
300 mg qw 
(N1 = 123)

***
54.2%

***
42.3%

0

10

20

30

40

50

60

70

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100

Placebo
(N1 = 17)

23.5%

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 <

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1

Dupilumab 
200 or 300 mg q2w

(N1 = 24)

Dupilumab 
300 mg q4w 

(N1 = 27)

33.3%

48.1%

Figure 4. Proportions of patients at Week 16 with: HADS-A < 11a, (A) SOLO and (B) ADOL; HADS-D < 11b, (C) SOLO and (D) ADOL; and  
HADS-A < 11c and HADS-D < 11c, (E) SOLO and (F) ADOL.

aAmong patients with HADS-A baseline values ≥ 11. bAmong patients with HADS-D baseline values ≥ 11. cAmong patients with baseline values ≥ 11 in ≥ 1 of HADS-A or HADS-D. ** P < 0.01; *** P ≤ 0.0001. 

–10

–9

–8

–7

–6

–5

–4

–3

–2

–1

0

Placebo 
(n = 460)

–1.6

L
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±
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E
)

Dupilumab 
300 mg q2w 

(n = 457)

(A) Dupilumab 
300 mg qw

(n = 462)

–5.1
*** –5.5

***

–10

–9

–8

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–6

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–4

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–1

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Placebo 
(n = 85)

–2.5

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Dupilumab 
200 or 300 mg q2w

(n = 82)

(B) Dupilumab 
300 mg q4w 

(n = 84)

–3.8

–5.2
*

–10

–9

–8

–7

–6

–5

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–1

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Placebo 
(n = 460)

–1.4

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Dupilumab 
300 mg q2w 

(n = 457)
(C)

Dupilumab 
300 mg qw

(n = 462)

–2.8
***

–3.0
***

–10

–9

–8

–7

–6

–5

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Placebo 
(n = 85)

–1.6

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Dupilumab 
200 or 300 mg q2w 

(n = 82)
(D)

Dupilumab 
300 mg q4w 

(n = 84)

–2.3
–2.7

–10

–9

–8

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–6

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–1

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Placebo 
(n = 460)

–0.5

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Dupilumab 
300 mg q2w 

(n = 457)
(E)

Dupilumab 
300 mg qw

(n = 462)

–2.3
***

–2.5
***

–10

–9

–8

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Placebo
(n = 85)

–0.8

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Dupilumab 
200 or 300 mg q2w 

(n = 82)
(F)

Dupilumab 
300 mg q4w 

(n = 84)

–1.4

–2.4
**

Figure 2. Change from baseline to Week 16 in: total HADS,  
(A) SOLO and (B) ADOL; HADS-A, (C) SOLO and (D) ADOL; and 
HADS-D, (E) SOLO and (F) ADOL.

* P < 0.05; ** P < 0.01; *** P ≤ 0.0001.

METHODS

Study design
• Detailed descriptions of the study populations and methodologies 

have been previously published,9,10 and are summarized below 
and in Figure 1

 – ADOL adolescent patients received 200/300 mg dupilumab 
q2w (patients with body weight < 60 kg received 200 mg of 
the study drug; patients with body weight ≥ 60 kg received 
300 mg), or 300 mg q4w, or placebo

Table 1. Baseline demographics and clinical characteristics.
Adult patients (SOLO 1 & 2 pooled) Adolescent patients (ADOL)

Placebo 
(n = 460)

Dupilumab  
300 mg q2w (n = 457)

Dupilumab  
300 mg qw (n = 462)

Placebo 
(n = 85)

Dupilumab  
200/300 mg q2w (n = 82)

Dupilumab  
300 mg q4w (n = 84)

Age, mean (SD), years 38.4 (14.03) 38.3 (14.37) 38.2 (14.48) 14.5 (1.78) 14.5 (1.74) 14.4 (1.59)
Male, n (%) 250 (54.3) 267 (58.4) 281 (60.8) 53 (62.4) 43 (52.4) 52 (61.9)
Duration of AD, mean (SD), years 28.8 (14.43) 27.9 (15.20) 27.6 (15.38) 12.3 (3.44) 12.5 (2.97) 11.9 (3.18)
Patients with IGA score = 4, n (%) 225 (48.9) 223 (48.8) 218 (47.2) 46 (54.1) 43 (52.4) 46 (54.8)
EASI score, mean (SD) 34.0 (14.38) 32.4 (13.32) 32.5 (13.34) 35.5 (13.97) 35.3 (13.84) 35.8 (14.82)
Peak Pruritus NRS score, mean (SD) 7.4 (1.81) 7.4 (1.76) 7.3 (1.94) 7.7 (1.62) 7.5 (1.52) 7.5 (1.84)
BSA affected by AD, mean (SD), % 55.8 (23.25) 53.7 (22.21) 54.1 (22.29) 56.4 (24.13) 56.0 (21.40) 56.9 (23.51)
SCORAD score, mean (SD) 68.8 (14.45) 67.1 (13.71) 67.5 (13.34) 70.4 (13.25) 70.6 (13.89) 69.8 (14.12)
POEM score, mean (SD) 20.6 (5.9) 20.3 (6.0) 20.7 (5.9) 21.1 (5.4) 21.0 (5.0) 21.1 (5.5)
(C)DLQI total score, mean (SD) 15.1 (7.47) 14.7 (7.25) 15.1 (7.47) 13.1 (6.72) 13.0 (6.21) 14.8 (7.38)
HADS total score, mean (SD) 13.2 (8.33) 13.0 (7.43) 13.7 (8.15) 11.6 (7.76) 12.6 (8.04) 13.3 (8.17)
HADS-A score, mean (SD) 7.4 (4.52) 7.3 (4.14) 7.4 (4.18) 7.4 (4.41) 8.1 (4.62) 8.0 (4.87)
 HADS-A ≥ 8, n (%) 183 (39.8) 196 (42.9) 209 (45.2) 41 (48.2) 47 (57.3) 42 (50.0)
 HADS-A ≥ 11, n (%) 108 (23.5) 97 (21.2) 97 (21.0) 17 (20.0) 24 (29.3) 25 (29.8)
HADS-D score, mean (SD) 5.7 (4.56) 5.7 (4.07) 6.2 (4.67) 4.3 (3.86) 4.4 (4.15) 5.2 (4.17)
 HADS-D ≥ 8, n (%) 139 (30.2) 148 (32.4) 160 (34.6) 14 (16.5) 19 (23.2) 23 (27.4)
 HADS-D ≥ 11, n (%) 71 (15.4) 61 (13.3) 75 (16.2) 6 (7.1) 8 (9.8) 10 (11.9)
EASI scores reported on scale from 0 to 72, Peak Pruritus NRS scores reported on scale from 0 to 10, SCORAD scores reported on scale from 0 to 103, POEM scores reported on scale from 0 to 28, (C)DLQI scores reported on scale from 0 to 30, 
HADS scores reported on scale from 0 to 21. BSA, body surface area; (C)DLQI, (Children’s) Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; n, number of patients; NRS, Numerical Rating 
Scale; POEM, Patient-Oriented Eczema Measure; SCORAD, SCORing Atopic Dermatitis; SD, standard deviation.

Table 2. Safety assessment during the treatment period.

Patients with event, n (%)

Adult patients (SOLO 1 & 2 pooled) Adolescent patients (ADOL)

Placebo 
(n = 456)

Dupilumab  
300 mg q2w  

(n = 465)

Dupilumab  
300 mg qw  
(n = 455)

Placebo 
(n = 85)

Dupilumab  
200/300 mg q2w 

(n = 82)

Dupilumab  
300 mg q4w 

(n = 83)
≥ 1 TEAE 313 (68.6) 321 (69.0) 307 (67.5) 59 (69.4) 59 (72.0) 53 (63.9)
TEAE leading to permanent study 
discontinuation

7 (1.5) 6 (1.3) 7 (1.5) 1 (1.2) 0 0

Death 0 0 1 (0.2)a 0 0 0
Treatment-emergent SAE 24 (5.3) 11 (2.4) 10 (2.2) 1 (1.2) 0 0
TEAEs occurring in ≥ 5% of patients in any group in any trial (PT)
  Dermatitis atopic 148 (32.5) 62 (13.3) 59 (13.0) 21 (24.7) 15 (18.3) 15 (18.1)
  Nasopharyngitis 39 (8.6) 42 (9.0) 45 (9.9) 4 (4.7) 3 (3.7) 9 (10.8)
  Upper respiratory tract infection 10 (2.2) 13 (2.8) 20 (4.4) 15 (17.6) 10 (12.2) 6 (7.2)
  Headache 24 (5.3) 40 (8.6) 33 (7.3) 9 (10.6) 9 (11.0) 4 (4.8)
  Injection-site reaction 28 (6.1) 51 (11.0) 72 (15.8) 1 (1.2) 0 1 (1.2)
Conjunctivitisb 10 (2.2) 45 (9.7) 33 (7.3) 4 (4.7) 8 (9.8) 9 (10.8)
aDeath was unrelated to treatment (for a full description of the events, see Simpson, et al. 20169); bIncludes the following PTs: conjunctivitis, conjunctivitis bacterial, conjunctivitis viral, conjunctivitis allergic, and atopic keratoconjunctivitis. MedDRA, 
Medical Dictionary for Regulatory Activities; PT, MedDRA Preferred Term; SAE, serious adverse event; TEAE, treatment-emergent adverse event.

References: 1. Weidinger S, Novak N. Lancet. 2016;387:1109-22. 2. Yu SH, Silverberg JI. J Invest Dermatol. 2015;135:3183-6. 3. Eckert L, et al. J Am Acad Dermatol. 2017;77:274-9. 4. Silverberg JI, et al. J Invest Dermatol. 2019;139:1388-91. 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. Nat Rev Drug Discov. 2016;15:35-50. 8. Gandhi NA, et al. Expert Rev Clin Immunol. 2017;13:425-37. 9. Simpson EL, et al. N Engl J Med. 2016;375:2335-48. 10. Simpson EL, et al. JAMA Derm. 2019; Nov 6 [Epub 
ahead of print]. doi: https://doi.org/10.1001/jamadermatol.2019.3336.

Acknowledgments: Data first presented at the 2020 Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI); Philadelphia, PA, USA; March 13–16, 2020.

Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02277743 (LIBERTY AD SOLO 1), NCT02277769 (LIBERTY AD SOLO 2), and NCT03054428 (LIBERTY AD ADOL). Medical writing/editorial assistance provided by Luke Shelton, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. 

Disclosures: Silverberg JI: AbbVie, Celgene, Eli Lilly, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Realm Therapeutics, Regeneron Pharmaceuticals, Inc. – investigator; AbbVie, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, MedImmune (AstraZeneca), Menlo Therapeutics, Pfizer, Realm Therapeutics, Regeneron Pharmaceuticals, Inc. – consultant; Regeneron Pharmaceuticals, Inc. – speaker. Soong W: AstraZeneca, Regeneron Pharmaceuticals, Inc. – speaker, advisory board member, investigator; AbbVie, Regeneron Pharmaceuticals, Inc. – consultant; AbbVie – investigator; Aimmune, GSK, LEO 
Pharma, Novartis, Pfizer, Teva, Vanda Pharmaceuticals – investigator grants; Genentech – investigator grants, honorarium, advisory board member; Stallergenes Greer – advisory board member. Lockshin B: Eli Lilly, Regeneron Pharmaceuticals, Inc. – investigator, speaker; Anacor, Dermira, Franklin Bioscience, LEO Pharma – investigator; AbbVie – investigator, speaker, consultant. Gadkari A, Chen Z, Bansal A: Regeneron Pharmaceuticals, Inc. − employees and shareholders.

CONCLUSIONS
• A large proportion of adult and adolescent patients with AD had symptoms of anxiety or depression at 

baseline, indicative of a high burden of AD
• Dupilumab monotherapy improved symptoms of anxiety and depression in adult and adolescent patients 

with AD, and was well tolerated with an acceptable safety profile

METHODS (cont.) RESULTS
Patients
• 1,379 adults were randomized in the SOLO trials, and 251 

adolescents were randomized in the ADOL trial

• Baseline demographics and characteristics were balanced 
between the treatment groups in the individual trials (Table 1)

• Adolescents had numerically higher baseline disease severity  
than adults

Efficacy assessment

Safety