BJD
C L I NI C A L T R I A L
Dupilumab treatment improves quality of life in adult
patients with moderate-to-severe atopic dermatitis: results
from a randomized, placebo-controlled clinical trial*
A. Tsianakas iD ,1 T.A. Luger1 and A. Radin2
1
Department of Dermatology, University of M€unster, M€unster, Germany
2
Regeneron Pharmaceuticals Inc., Tarrytown, NY, U.S.A.
Linked Comment: Rencz. Br J Dermatol 2018; 178:319–320.
Correspondence
Athanasios Tsianakas.
E-mail: Athanasios.Tsianakas@ukmuenster.de
Accepted for publication
15 August 2017
Funding sources
This study was funded by Sanofi and Regeneron
Pharmaceuticals Inc. Editorial assistance was pro-
vided by Jamie Lim, PhD, of Excerpta Medica,
funded by Sanofi Genzyme and Regeneron Pharma-
ceuticals Inc.
Conflicts of interest
A.T. is a consultant for Biogen-IDEC, Celgene,
Novartis, Pfizer; T.A.L. is a consultant for Abbvie,
Anacor, Biogen-IDEC, Ceries, Celgene, Galderma,
Eli-Lilly, Janssen-Cilag, La Roche Posay, Meda,
Merz, MSD, Novartis, Pfizer, Sandoz, Sanofi-Aven-
tis, Symrise, Wolff and Ziarco; A.R. is an
employee and shareholder of Regeneron Pharmaceu-
ticals Inc.
*Plain language summary available online
DOI 10.1111/bjd.15905
406 British Journal of Dermatology (2018) 178, pp406–414
British Journal of Dermatology
Summary
Background Dupilumab, a human anti-interleukin-4 receptor alpha monoclonal
antibody, significantly improved clinical signs and symptoms in adults with
moderate-to-severe atopic dermatitis in a randomized, double-blind, placebo-
controlled, phase IIa trial.
Objectives We evaluate health-related quality of life (HRQoL) and correlation of
HRQoL with secondary clinical and patient-reported outcomes in a subset of
patients from this trial of dupilumab.
Methods Patients were randomized to 300 mg weekly subcutaneous dupilumab or
placebo for 12 weeks (trial registration: NCT01548404). The Quality of Life Index
of Atopic Dermatitis (QoLIAD) score (exploratory outcome) and its correlation with
efficacy outcomes [Eczema Area and Severity Index (EASI); primary end point;
SCORing Atopic Dermatitis (SCORAD), SCORAD visual analogue scale (VAS) scores
for sleep and pruritus, pruritus numerical rating scale (NRS) and 5-dimensional
pruritus] were assessed in 64 adults with moderate-to-severe atopic dermatitis.
Results Mean QoLIAD scores at baseline  standard error (SE) were 13
3  1
34
and 11
3  1
09 for the placebo and dupilumab groups, respectively. Dupilumab
significantly improved QoLIAD score after 12 weeks of treatment vs. placebo
(mean % change from baseline in QoLIAD score  SE: 64
0  6
91 vs. –
11
1  9
31). Least squares mean % difference from baseline vs. placebo in
QoLIAD score SE was 52
0  11
43, P < 0
001). QoLIAD scores significantly
correlated with changes in efficacy outcomes, including EASI (r = 0
44), 5-dimen-
sional pruritus (r = 0
49), pruritus NRS (r = 0
41), total SCORAD (r = 0
56) and
SCORAD VAS scores for sleep (r = 0
47) and pruritus (r = 0
54); all P < 0
05.
Conclusions Dupilumab improved QoLIAD scores in adults with atopic dermatitis
and was significantly associated with improvements in study outcomes.
What’s already known about this topic?
• Dupilumab has demonstrated efficacy and tolerability in phase II and III clinical tri-
als with adults with moderate-to-severe atopic dermatitis.
What does this study add?
• We report results from a 12-week phase IIa study, which shows improvement in
quality of life and efficacy outcomes in a subset of patients treated with dupilumab;
quality of life was significantly associated with improvements in study outcomes.
• These data support continued evaluations of dupilumab as a patient-relevant treat-
ment for atopic dermatitis.
© 2017 British Association of Dermatologists
 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al. 407
Atopic dermatitis is a skin disease with high prevalence among
children (15–30%) and adults (2–10%).1 Atopic dermatitis
has a substantial impact on the health-related quality of life
(HRQoL) of patients, partly because of the chronic inflamma-
tion with severe pruritus and comorbid skin disorders, such as
bacterial and viral superinfections, associated with atopic der-
matitis.2 Onset of atopic dermatitis results from multiple inter-
nal (genetic) and external factors affecting the epidermal
barrier as well as innate and adaptive skin immune system
components.3–8 In particular, upregulation of type 2 T helper
cell (Th2) immune responses seem to play a pivotal role in
the induction of atopic dermatitis.9–11 The Th2 cytokines
interleukin (IL)-4 and IL-13 are key drivers of Th2 immune
(atopic/allergic) diseases, such as atopic dermatitis and
asthma,12 and share the same receptor subunit, in IL-4 recep-
tor alpha (IL-4Ra), on immune cells, including B cells and
monocytes, and some types of nonimmune cells (e.g. fibrob-
lasts).13,14
The treatment of atopic dermatitis, a disease that currently
cannot be cured, represents a major challenge. Although topi-
cal therapy is usually effective for mild disease,15 treatment of
moderate-to-severe disease is more difficult, and often
includes immune-modulating drugs that are of limited use
because of their unfavourable safety profile.16 Dupilumab is a
fully human monoclonal antibody directed against the IL-4Ra
subunit that inhibits IL-4 and IL-13 signalling, and is a novel
therapeutic approach for atopic/allergic diseases. Dupilumab is
the first targeted biological therapy approved by the U.S. Food
and Drug Administration for the treatment of adults with
moderate-to-severe atopic dermatitis whose disease is inade-
quately controlled by topical treatments, or when such treat-
ments are not advisable.
In clinical trials in patients with atopic dermatitis,17–20
asthma21,22 or chronic sinusitis with nasal polyposis,23 dupilu-
mab demonstrated efficacy and an acceptable safety profile. In
a phase IIa randomized, double-blind, placebo-controlled trial
enrolling adults with moderate-to-severe atopic dermatitis
inadequately controlled by topical medications,17 12 weeks of
treatment with subcutaneous dupilumab 300 mg weekly sig-
nificantly improved clinical outcomes compared with placebo,
including Eczema Area and Severity Index (EASI) score, per-
centage of body surface area (BSA) affected with atopic der-
matitis, pruritus numerical rating scale (NRS) score,
proportion of patients achieving a reduction of ≥ 50% or ≥
75% in EASI score (EASI 50, EASI 75), and the proportion of
patients with an Investigator’s Global Assessment (IGA) score
of 0 (clear) or 1 (almost clear).
Here we present the effect of dupilumab on HRQoL in a
subpopulation of patients using the Quality of Life Index of
Atopic Dermatitis (QoLIAD)24,25 (exploratory end point) and
report the efficacy outcomes in this subset. To demonstrate
the association of HRQoL with clinical measures of efficacy
and patient-reported outcomes (PROs), we also present corre-
lations of QoLIAD with clinical outcomes and PROs from this
trial.
© 2017 British Association of Dermatologists
Patients and methods
Detailed descriptions of the study population and methodol-
ogy have already been published,17 and are briefly summa-
rized below.
Study design
This randomized, double-blind, placebo-controlled phase IIa
study consisted of a 12-week treatment period followed by a
16-week safety follow-up (protocol number R668-AD-1117,
ClinicalTrials.gov number: NCT01548404; EudraCT number
2011-003836-29). Patients were randomly assigned (1 : 1) to
receive subcutaneous injections of 300 mg dupilumab or pla-
cebo once weekly for 12 weeks. A central randomization
scheme was used, provided by an interactive response technol-
ogy system to the designated study pharmacist or qualified
designee. Drug kits were coded, masking the treatment
assigned.
The study was conducted in accordance with Good Clinical
Practice guidelines and adhered to the ethical principles of the
Declaration of Helsinki. All study documents and procedures
were approved by the appropriate institutional review boards
and ethics committees at each study site; each patient provided
written informed consent before study participation. The study
was initiated (first patient, first visit) on 3 April 2012 and
ended with the last patient visits on 25 June 2013.
Study population
Eligible patients were adults (age ≥ 18 years) with moderate-
to-severe atopic dermatitis; an IGA score of 3 (moderate) or 4
(severe), a ≥ 10% BSA with atopic dermatitis, and an EASI
score ≥ 16 at screening and baseline visits; and inadequate
response to topical medications. Patients had experienced the
condition for 3 years or more before the screening visit. The
study was conducted at 23 sites in Europe.
End points
Table S1 (see Supporting Information) provides details of the
efficacy outcome measures. The primary efficacy end point at
week 12 was the percentage change from baseline in EASI
score (scale range 0–72, with higher score indicating greater
severity).26,27 Secondary end points included: total SCORing
Atopic Dermatitis (SCORAD) score [scale 0–103; higher score
indicates greater severity and a score change of 8
7 is the min-
imal clinically important difference (MCID)],27,28 5-dimen-
sional (5-D) pruritus score (scale 5–25, with higher score
indicating greater itch)29 and pruritus NRS score (scale 0–10;
higher score indicates worse itch),30 the proportion of patients
achieving EASI 50 or EASI 75 and an IGA of 0 or 1 (scale 0,
clear to 4, severe).31 The PRO components of total SCORAD
score, SCORAD visual analogue scale (VAS) scores for pruritus
and sleep loss, were also assessed (scale range 0–10, higher
British Journal of Dermatology (2018) 178, pp406–414
408 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al.

QoLIAD
All items answered as a yes/no response
1. I worry about my appearance. 14. I worry that people will not accept me
2. I have no self-confidence. 15. I hate seeing myself in the mirror.
3. I avoid physical contact. 16. I find it hard to relax.
4. I get embarrassed when I am with people I 17. I can’t concentrate on anything else.
don’t know very well.
5. My life revolves around my condition. 18. I lose a lot of time to my eczema.
6. I feel tense all the time. 19. I am embarrassed about my appearance.
7. I want to shut myself away. 20. There is no release from it.
8. I can’t wear the clothes I want to wear. 21. I worry about meeting people.
9. I feel that people don’t want to touch me. 22. It stops me from doing the things I want to
do.
10. It is always on my mind. 23. I have to push myself to do things.
11. I don’t want people to see my skin. 24. The eczema affects everything I do.
12. It affects my concentration. 25. I can’t bear anyone touching me.
13. I sometimes feel like crying.

Fig 1. Quality of Life Index of Atopic Dermatitis (QoLIAD), a 25-item scoring instrument to assess quality of life in patients with atopic
dermatitis.

score indicates greater itch/sleep loss), but were not prespeci-
fied study end points.
HRQoL, as measured by QoLIAD,24,25 was an exploratory
end point and was assessed in German and French patients in
this study. As a result of the limited availability of the QoLIAD
questionnaire in different languages, the remaining patients
from study sites in Hungary, Poland and Czech Republic were
unable to complete the questionnaire. QoLIAD is a 25-item,
validated questionnaire used in clinical practice and trials to
assess the impact of atopic dermatitis symptoms on HRQoL
(Fig. 1). The score range is 0–25 (higher score indicates
poorer HRQoL). Using distribution and anchor-based methods
of interpreting QoLIAD scores, a score change of 2–3 was esti-
mated to be the MCID.25
In addition, the QoLIAD score was evaluated with respect
to change from baseline in other clinical efficacy parameters
and PROs: EASI; pruritus NRS; 5-D pruritus; SCORAD and
SCORAD VAS scores for pruritus and sleep loss at baseline
and after 12 weeks of dupilumab treatment. All primary and
secondary efficacy end points, as well as SCORAD VAS scores
for pruritus and sleep loss, were assessed in the QoLIAD
subset.

Table 1 Baseline demographics and clinical characteristics in the Quality of Life Index of Atopic Dermatitis (QoLIAD) subset

P-value,
QoLIAD subset
P-value, dupilumab 300 mg (n = 64) vs.
Dupilumab 300 mg Placebo, weekly All treatment weekly vs. placebo non-QoLIAD
Characteristic weekly (n = 32) (n = 32) groups (n = 64) weekly – QoLIAD subset subset (n = 45)
Age (years) 37
3  1
8 40
7  2
1 39
0  1
4 0
228 0
008
Sex, men 19 (59) 17 (53) 36 (56) 0
504 0
547
Ethnicity, white 32 (100) 32 (100) 64 (100) N/A N/A
Body mass index 25
6  0
9 23
6  0
7 24
6  0
6 0
091 0
097
Duration of atopic dermatitis, years 29
8  2
3 27
3  2
2 28
6  1
6 0
436 0
010
EASI scorea 26
4  2
4 27
3  2
4 26
8  1
7 0
796 0
010
IGA scoreb 3
8  0
1 3
9  0
1 3
9  0
1 0
480 0
337
SCOring Atopic Dermatitis score 65
4  2
4 65
7  2
2 65
6  1
6 0
906 0
034
Body surface area affected, % 40
9  4
1 41
9  3
9 41
4  2
8 0
860 < 0
001
5-dimensional pruritus scorec 18
0  0
5 18
5  0
6 18
2  0
4 0
562 0
248
Pruritus NRS scored 5
7  0
2 5
5  0
3 5
6  0
2 0
499 0
011

Data are denoted as n (%) or mean  standard error. aScores on the Eczema Area and Severity Index (EASI) range from 0 to 72, with higher
scores indicating greater severity; bInvestigator’s Global Assessment (IGA) scores of the severity of atopic dermatitis range from 0 (clear) to 5
(very severe); cFive-dimensional pruritus was scored on a scale of 5–25, with higher scores indicating greater itch; dscores on the pruritus
numerical rating scale (NRS) range from 0 to 10, with higher score indicating worse itch.

British Journal of Dermatology (2018) 178, pp406–414 © 2017 British Association of Dermatologists
 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al. 409

Study week
0 4 8 12
0

Mean % change from baseline

–10

–20

in QoLIAD ± SE
–30

–40

–50

–60
Placebo weekly
–70
Dupilumab 300 mg weekly
–80

Fig 2. Percentage change in Quality of Life Index of Atopic Dermatitis (QoLIAD) over time. The mean percentage change from baseline in
QoLIAD score to week 12 in a subset of patients (n = 64) with moderate-to-severe atopic dermatitis. At week 4: LS mean % difference vs.
placebo  SE: 39
7  11
62 (95% CI 62
96 to 16
46, P = 0
001); at week 12: LS mean % difference vs. placebo  SE: 52
0  11
43
(95% CI 74
87 to 29
11, P < 0
001). LS, least square, CI, confidence interval; SE, standard error.

Safety was assessed in the study by evaluating the incidence
of treatment-emergent adverse events (TEAEs). Safety assess-
ments included assessment of vital signs, physical examina-
tion, clinical laboratory testing and electrocardiography. Safety
outcomes have been previously reported.17
Statistics
Statistical tests used have been previously reported.17 Out-
comes are reported as mean percentage change from baseline
to associated standard errors (SEs) by treatment group, as well
as the difference of the least squares means estimates vs. pla-
cebo, with their corresponding SEs and associated 95% confi-
dence intervals (CIs). Pearson’s correlation coefficient analysis
was used to assess the statistical significance of the relationship
between the efficacy data and QoLIAD scores. The statistical
tests used were two-sided at an overall 0
049 significance
level. Statistical analyses were performed using SAS software,
version 9 (SAS Institute, Cary, NC, U.S.A.).
Continuous efficacy variables were analysed using an ANCOVA
model with treatment and baseline IgE (< 150 kU L 1 vs. ≥
150 kU L 1 at screening) as the fixed effects, and the relevant
baseline value as a covariate. Comparisons between dupilu-
mab- and placebo-treated groups were analysed using a
Cochran–Mantel–Haenszel test, stratified by baseline IgE level.
Missing data were imputed using the last-observation-carried-
forward approach, and efficacy data were set to missing after
rescue medication was used.
Results
Study population
A total of 109 patients were randomized and received one or
more doses of the study drug; all patients were included in
the safety analysis. Enrolment and disposition of patients in
the total study population have been previously reported.17
The baseline demographics and clinical characteristics of the
64 patients in the QoLIAD subset were not significantly differ-
ent in the dupilumab and placebo groups (Table 1). The base-
line demographics and clinical characteristics of the 64
patients in the QoLIAD subset and the remaining 45 patients
in the study population were similar except for significant dif-
ferences in age, disease duration, BSA, EASI, SCORAD and pru-
ritus NRS scores (Table 1).
Quality of life and efficacy in the Quality of Life Index of
Atopic Dermatitis subset
Dupilumab resulted in significant improvement in QoLIAD
score compared with placebo from baseline to week 12 in the
QoLIAD subset (Fig. 2, P < 0
001, Table S2; see Supporting
Information). Mean QoLIAD score at baseline  SE was
13
3  1
34 and 11
3  1
09 for the placebo and dupilumab
groups, respectively.
A significant benefit in HRQoL was achieved as early as
week 4 (P = 0
001). Importantly, the mean change from
baseline in QoLIAD at week 12  SE exceeded the MCID of
2–3 in the dupilumab group vs. placebo: 6
8  0
90 vs.
1
1 1
07. Notably, dupilumab treatment significantly
improved efficacy outcomes in the QoLIAD subpopulation for
all end points assessed (Fig. 3a–h, Table S2; see Supporting
Information). For example, dupilumab resulted in a reduction
from baseline of 20
6  1
97 in EASI score at week 12,
which was greater than that observed with placebo
(6
3  2
04) and exceeded the MCID of 6
6.
In the dupilumab group, the correlations between change
in QoLIAD score and change in clinical outcomes and PROs
from baseline to week 12 were significant and ‘moderate’ (de-
fined as r = 0
40–0
59) for all outcomes (Table 2): EASI score

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp406–414
410 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al.

20 (a)

Mean % change from baseline in

40

SCORAD VAS score for sleep

(e)
Mean % change from baseline Study week 20
0
0 1 2 3 4 5 6 7 8 9 10 11 12 0
in EASI score ± SE
0 1 2 3 4 5 6 7 8 9 10 11 12

loss ± SE
–20 –20 Study week

–40
–40
Placebo weekly –60
Dupilumab 300 mg weekly Placebo weekly
–60 –80
Dupilumab 300 mg weekly
–100
–80

100
–100

Mean % change from baseline in

80 (f)

SCORAD VAS score for

Placebo weekly
60
Patients achieving EASI 50 (%)

100 Dupilumab 300 mg weekly

(b) 40
90

pruritus ± SE
80 20

70 0
0 1 2 3 4 5 6 7 8 9 10 11 12
60 –20
Study week
50 –40
40 –60
30 –80
20 Placebo weekly –100
10 Dupilumab 300 mg weekly
(g)
Study week
0 0 2 4 6 8 10 12
0 1 2 3 4 5 6 7 8 9 10 11 12 0
Mean % change from baseline in

Study week
–10
5-D pruritus score ± SE

100 (c)
Patients achieving EASI 75 (%)

90 Placebo weekly –20 Placebo weekly

Dupilumab 300 mg weekly
Dupilumab 300 mg weekly
80
70 –30

60
–40
50
40
–50
30
20 –60
10
20
0
0 1 2 3 4 5 6 7 8 9 10 11 12 (h)
Mean % change from baseline

10 Study week
in pruritus NRS score ± SE

Study week 0
0 1 2 3 4 5 6 7 8 9 10 11 12
(d) –10
Study week *
0 –20
Placebo weekly
0 1 2 3 4 5 6 7 8 9 10 11 12
Mean % change from baseline

–30 Dupilumab 300 mg weekly

–10
in total SCORAD score

–40

–20 –50 †
–60
–30 Placebo weekly
Dupilumab 300 mg weekly –70

–40 –80

–50

–60

–70

British Journal of Dermatology (2018) 178, pp406–414 © 2017 British Association of Dermatologists
 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al. 411

Fig 3. Efficacy over time to week 12 in the subset of patients assessed with the Quality of Life Index of Atopic Dermatitis (QoLIAD) (n = 64)
with moderate-to-severe atopic dermatitis (AD). (a) Mean percentage change from baseline in Eczema Area and Severity Index (EASI) score. At
week 1: LS mean % difference vs. placebo  SE: 27
8  8
01 (95% CI 43
86 to 11
80, P = 0
001); at week 12: LS mean % difference vs.
placebo  SE 54
2  8
94 (95% CI 72
08 to 36
30, P < 0
001). Proportion of patients achieving (b) ≥ 50% reduction in EASI score (EASI
50, week 2: P = 0
003 and week 12: P < 0
001) and (c) ≥ 75% reduction in EASI score (EASI 75, week 4: P = 0
002 and week 12: P < 0
001).
(d) Mean percentage change from baseline in total SCORing Atopic Dermatitis (SCORAD) score. At week 1: LS mean % difference vs.
placebo  SE: 15
8  4
45 (95% CI 24
72 to 6
90, P < 0
001; at week 12: LS mean % difference vs. placebo  SE: 43
8  6
73 (95%
CI 57
24 to 30
33, P < 0
001. Mean percentage change from baseline in SCORAD visual analogue scale (VAS) scores for (e) sleep loss [at
week 5: LS mean % difference vs. placebo  SE: 43
1  16
36 (95% CI 75
84 to 10
26, P = 0
011); at week 12: LS mean % difference vs.
placebo  SE: 65
6  17
78 (95% CI 101
27 to 30
01, P < 0
001)] and (f) pruritus [at week 2: LS mean % difference vs. placebo  SE:
38
8  10
64 (95% CI 60
03 to 17
48, P = 0
001); at week 12: LS mean % difference vs. placebo  SE: 71
2  15
90 (95% CI
102
99 to 39
38, P < 0
001). (g) Mean percentage change from baseline five-dimensional (5-D) pruritus score. At week 2: LS mean %
difference vs. placebo  SE: 18
5  4
28 (95% CI 27
01 to 9
98, P < 0
001); at week 12: LS mean % difference vs. placebo  SE:
39
3  5
06 (95% CI 49
38 to 29
14, P < 0
001). (h) Mean percentage change from baseline average weekly pruritus numerical rating
scale (NRS) score. At week 1: LS mean % difference vs. placebo  SE: 24
3  6
60 (95% CI 37
56 to 11
14, P = 0
001); and at week 12:
LS mean % difference vs. placebo  SE: 50
5  9
27 (95% CI 69
02 to 31
89, P < 0
001). LS, least square, CI, confidence interval; SE,
standard error.

(r = 0
44, P = 0
013); 5-D pruritus score (r = 0
49,
P = 0
004); pruritus NRS score (r = 0
41, P = 0
023);
SCORAD score (r = 0
56, P = 0
001); SCORAD VAS score for
sleep loss (r = 0
47, P = 0
007); and SCORAD VAS score for
pruritus (r = 0
54, P = 0
001). In contrast, in the placebo
group, the correlations were nonsignificant and ‘very weak to
weak’ (r = 0
00–0
39) for all these end points, except EASI
score, which was ‘moderate’ and significant (Table 2;
r = 0
43, P = 0
014).
For the dupilumab and placebo groups combined, the cor-
relations between the change in QoLIAD score and change in
clinical end points from baseline to week 12 were significant
and ‘moderate’ for all end points (P < 0
05) except SCORAD
VAS scores for sleep loss and pruritus, which were ‘weak’
(r = 0
20–0
39), but significant (Table 2; P = 0
036 and
P = 0
009, respectively). Correlations at baseline for dupilu-
mab and placebo treatment groups combined were generally
weaker compared with correlations at week 12 for most effi-
cacy end points (Table 2).
Safety in the Quality of Life Index of Atopic Dermatitis
subset
Safety outcomes in the overall population of this study have
been previously reported.17 In the QoLIAD subset, the most
common TEAEs were nasopharyngitis, headache and fatigue,
which were reported more frequently in the dupilumab group
compared with placebo. Most TEAEs were mild or moderate
and transient. Patient discontinuation rates during treatment as
well as skin infections were higher in the placebo group com-
pared with dupilumab (Table 3).
Discussion
Our data show that dupilumab improved clinical responses in a
subset of adults with moderate-to-severe atopic dermatitis.
Patients treated with dupilumab experienced rapid relief from
clinical signs such as eczema and their concomitant subjective
symptoms, including sleep loss and pruritus. Importantly, dupi-
lumab also significantly improved the HRQoL of patients as
measured with the QoLIAD, exceeding the MCID of 2–3. Of
note, a significant improvement in QoLIAD score was already
achieved after 4 weeks of dupilumab treatment, which was the
earliest measured time point after baseline.
The efficacy outcomes with dupilumab treatment in the
QoLIAD subpopulation were consistent with those in the overall
study population as previously reported.17 Moreover, in con-
trast with mostly nonsignificant, ‘very weak to weak’ correla-
tions in the placebo group, correlations between change in
HRQoL and changes in all clinical and PRO parameters in dupi-
lumab-treated patients at week 12 were significant and ‘moder-
ate’. Furthermore, the overall incidence of TEAEs in the
QoLIAD subset was comparable between the dupilumab and
placebo groups, with most TEAEs reported as mild or moderate
and transient.
Pruritus, as the leading subjective sign of atopic dermatitis,
has a direct impact on many aspects of HRQoL, such as sleep
and social interaction, which are heavily impaired among
adults with atopic dermatitis.32–34 The presented HRQoL data
therefore suggest that dupilumab is a patient-relevant treat-
ment for atopic dermatitis.
Correlations of change in pruritus NRS score and the
changes in individual SCORAD VAS scores for pruritus and
sleep loss with QoLIAD score provide an overview of the asso-
ciation between distinct clinical symptoms and the HRQoL of
adults with moderate-to-severe atopic dermatitis. Pruritus and
loss of sleep have been reported as the most frequent and dis-
ruptive symptoms in adult atopic dermatitis.32,35 However,
sleep disturbance may be regarded as a consequence of pruri-
tus, rather than a symptom itself.
Accordingly, in previous studies,32,36 both objective and
patient-reported pruritus and sleep disturbances were shown
to be associated. Furthermore, the significant correlation
observed between QoLIAD and sleep loss scores in patients

© 2017 British Association of Dermatologists British Journal of Dermatology (2018) 178, pp406–414
412 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al.

Table 2 Correlations of Quality of Life Index of Atopic Dermatitis Table 2 (continued)

(QoLIAD) score and study outcomes at baseline and correlations of
change in QoLIAD and change in study outcomes at week 12 (last- Dupilumab Placebo
observation-carried-forward analysis)a 300 mg weekly weekly All treatment
(n = 32) (n = 32) groups (n = 64)

Dupilumab Placebo P-value 0
004 0
563 < 0
001

300 mg weekly weekly All treatment QoLIAD score vs.
(n = 32) (n = 32) groups (n = 64) pruritus NRS
scoreb
Correlations of
r-value 0
41 0
03 0
40
QoLIAD score
P-value 0
023 0
875 0
001
and study
QoLIAD score vs.
outcomes at
SCORAD score
baseline
r-value 0
56 0
19 0
54
QoLIAD score vs.
P-value 0
001 0
289 < 0
001
Eczema Area and
QoLIAD score vs.
Severity Index
SCORAD VAS
score
score for sleep
r-value 0
33 0
30 0
31
loss
P-value 0
068 0
094 0
012
r-value 0
47 0
17 0
26
QoLIAD score vs.
P-value 0
007 0
340 0
036
5-dimensional
QoLIAD score vs.
pruritus score
SCORAD VAS
r-value 0
46 0
32 0
38
score for
P-value 0
008 0
071 0
002
pruritus
QoLIAD score vs.
r-value 0
54 0
17 0
33
pruritus NRS
P-value 0
001 0
342 0
009
score
r-value 0
34 0
23 0
25 NRS, numerical rating scale; SCORAD, SCORing Atopic Dermati-
P-value 0
060 0
204 0
044 tis; VAS, visual analogue scale. aCorrelation was assessed using
QoLIAD score vs. Pearson’s correlation coefficient, denoted as the r-value in the
SCORAD score table; bdata were available for 31 patients in the dupilumab
r-value 0
50 0
37 0
42 group and 30 patients in the placebo group.
P-value 0
004 0
037 0
001
QoLIAD score vs.
SCORAD VAS
Table 3 Treatment-emergent adverse events (TEAEs) in the Quality of
score for sleep
Life Index of Atopic Dermatitis (QoLIAD) subset during the study
loss
r-value 0
41 0
24 0
32 period (28 weeks)
P-value 0
021 0
185 0
010
QoLIAD score vs. Dupilumab Placebo All treatment
SCORAD VAS 300 mg weekly weekly groups
score for (n = 32) (n = 32) (n = 64)
pruritus Patients with:
r-value 0
40 0
21 0
27 Any TEAE 29 (91) 29 (91) 58 (91)
P-value 0
022 0
241 0
031 Any serious TEAE 0 6 (19) 6 (9)
Correlations of Discontinuation 0 6 (19) 6 (9)
change in because of TEAE
QoLIAD score Skin infections 2 (6) 6 (19) 8 (13)
and change in Death 0 0 0
study outcomes Most common TEAEs:a
at week 12 Nasopharyngitis 18 (56) 9 (28) 27 (42)
QoLIAD score vs. Headache 6 (19) 4 (13) 10 (16)
Eczema Area and Fatigue 4 (13) 3 (9) 7 (11)
Severity Index
score Data are denoted as n (%). aExpressed by preferred term and
r-value 0
44 0
43 0
57 occurring in ≥ 10% of patients, which have a greater frequency
P-value 0
013 0
014 < 0
001 in the dupilumab treatment arm compared with placebo.
QoLIAD score vs.
5-dimensional
pruritus score
r-value 0
49 0
11 0
49 receiving dupilumab suggests that the improvement in sleep is
associated with an improvement in the HRQoL of patients
(continued)
treated with dupilumab. This may not be surprising, as sleep

British Journal of Dermatology (2018) 178, pp406–414 © 2017 British Association of Dermatologists
 Dupilumab and quality of life in adults with atopic dermatitis, A. Tsianakas et al. 413
disturbance may result in daytime sleepiness and fatigue, neg-
atively affecting functional activities, mood and overall mental
and physical health.37 Conversely, QoLIAD specifically assesses
the HRQoL of patients in relation to mental well-being,
encompassing parameters such as feelings of embarrassment,
anxiety, insecurity, mental preoccupation with the disease,
concentration and overall mood, which could affect a patient’s
ability to fall asleep; improvements in HRQoL may also lead
to improvements in sleep. Therefore, dupilumab seems to
have the potential not only to decrease substantially disease
activity in patients, but also to improve rapidly their HRQoL.
An analysis of data from adults with moderate-to-severe
atopic dermatitis enrolled in a phase IIb study of dupilumab
demonstrated that disease burden at screening is substantial
from a patient’s perspective, having an impact on both mental
and physical functioning, including their HRQoL.32 In that
study, HRQoL was assessed by the Dermatological Quality of
Life Index (DLQI),38 a standardized measure for assessing the
impact of dermatological conditions on health status, and 5-D
EuroQoL 3-level version (EQ-5D-3L),39 which is a standard-
ized instrument for measuring generic health status. Another
analysis of the phase IIb patient population that sought to
evaluate the effect of dupilumab treatment on PROs demon-
strated early and sustained improvements in sleep, mental
health and HRQoL, as assessed by SCORAD VAS score for
sleep, Patient-Oriented Eczema Measure, the Hospital Anxiety
and Depression Scale, the EQ-5D-3L and DLQI in patients trea-
ted with dupilumab compared with placebo.40
Furthermore, in recent phase III clinical trials (short and
longer term), dupilumab also improved these measures,
including the HRQoL measures DLQI19,20 and EQ-5D-3L;41
SCORAD VAS score for sleep was not reported and the
QoLIAD was not assessed. In the present subanalysis of the
phase IIa study, we analysed the effect of dupilumab on the
HRQoL of adults with moderate-to-severe atopic dermatitis,
as assessed by the QoLIAD, a questionnaire that was devel-
oped specifically for adults with atopic dermatitis.24 The
observed moderate, significant correlations between the
QoLIAD and the clinical outcome measures for dupilumab
and placebo patients combined at week 12, suggest that the
QoLIAD may be a reliable measure for assessing whether
drug treatment improves the parameters assessed by the
QoLIAD and, in particular, the HRQoL of adults with moder-
ate-to-severe atopic dermatitis.
Furthermore, although TEAEs were balanced overall between
the dupilumab and placebo groups in the QoLIAD subset,
patients in the placebo group had a higher rate of skin infec-
tions. This may have contributed to the significant difference
observed in improvement in the QoLIAD scores of patients in
the dupilumab and placebo groups. However, this finding was
not replicated in the phase IIb study of dupilumab in adults
with moderate-to-severe atopic dermatitis.18 In the phase III
studies, rates of skin infections were numerically higher in the
placebo than dupilumab groups.19,20 Overall, safety outcomes
in the QoLIAD subset were similar to those reported in the
overall population.17
© 2017 British Association of Dermatologists
Limitations include that the QoLIAD was assessed in a small
subset of the overall study population (64 patients in total), as
the questionnaire was available in a limited number of different
languages. The results are therefore representative of only half
the study population, as reflected by the significant differences
in a number of baseline demographics and clinical characteris-
tics between the QoLIAD subset and remaining patients in the
study population. Moreover, the QoLIAD is a disease-specific
HRQoL measure and therefore does not capture the impact of
adverse events, such as nasopharyngitis on quality of life.
Taken together, dupilumab represents a novel class of bio-
logics that is able to improve clinical signs and symptoms of
atopic dermatitis, and ultimately HRQoL, in a very effective
manner with an acceptable safety profile in patients with ato-
pic dermatitis. Future studies are needed to confirm improve-
ments in QoLIAD scores in a larger population of patients
from different ethnic backgrounds.
Acknowledgments
We thank the patients who participated in this study, the co-
investigators for their contribution to the study and staff at the
participating centres, and the following contributors from the
sponsors for providing support with the publication process
and critical review of the manuscript content: Vera Mastey,
Abhijit Gadkari and Linda Williams from Regeneron Pharma-
ceuticals Inc. and Laurent Eckert and Dianne Barry from Sanofi.
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Supporting Information
Additional Supporting Information may be found in the online
version of this article at the publisher’s website:
Table S1 Efficacy end points.
Table S2 Study outcomes at baseline and week 12 (last-
observation-carried-forward analysis; Quality of Life Index of
Atopic Dermatitis subset).
Powerpoint S1 Journal Club Slide Set.
© 2017 British Association of Dermatologists