Patient burden of moderate to severe atopic dermatitis

(AD): Insights from a phase 2b clinical trial

of dupilumab in adults
Eric L. Simpson, MD, MCR,a Thomas Bieber, MD,b Laurent Eckert, PhD,c Richard Wu, PhD,d
Marius Ardeleanu, MD,d Neil M. H. Graham, MD,d Gianluca Pirozzi, MD, PhD,c and Vera Mastey, MScd
Portland, Oregon; Bonn, Germany; Bridgewater, New Jersey; and Tarrytown, New York

Background: The adult burden of atopic dermatitis (AD) is poorly characterized.

Objective: We sought to characterize AD burden in adults with moderate to severe disease from the
patient’s perspective.

Methods: Patient-reported outcomes collected at screening in a phase 2b clinical trial of dupilumab

included pruritus numeric rating scale, 5-Dimension Pruritus Scale, subjective components of SCORing AD,
Patient-Oriented Eczema Measure, Hospital Anxiety and Depression Scale, Dermatology Life Quality Index,
and 5-Dimension EuroQol.

Results: Most of the 380 patients had been living with AD for nearly all their lives, whereas approximately
40% were given a diagnosis as adults; 40.3% had asthma and 60.5% had other allergic conditions. Despite
48.2% of patients using systemic therapies in the past year, patients reported problems with itch frequency
(85% of patients), duration (41.5% reported itching $18 h/d), and severity (6.5 of 10 on numeric rating
scale); 55% reported AD-related sleep disturbances 5 d/wk or more. Hospital Anxiety and Depression Scale
scores suggesting clinically relevant anxiety or depression were reported by 21.8% of patients. Quality of
life was impaired on Dermatology Life Quality Index and 5-dimension EuroQol.

Limitations: This study had limited generalizability; conclusions may not reflect those with mild AD or not
participating in a clinical trial.

Conclusions: Adults with moderate to severe AD report multidimensional burden including disease
activity, patient-reported symptoms, comorbidities, and quality-of-life impact. ( J Am Acad Dermatol
2016;74:491-8.)

Key words: adults; atopic dermatitis; burden of illness; patient-reported outcomes; pruritus; quality of life.

From the Department of Dermatology, Oregon Health and Science
Universitya; Department of Dermatology and Allergy, University
of Bonnb; Sanofi, Bridgewaterc; and Regeneron Pharmaceuti-
cals, Inc, Tarrytown.d
Supported by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial
support for the preparation of this manuscript was provided by
E. Jay Bienen, PhD, funded by Regeneron Pharmaceuticals, Inc.
Disclosure: Dr Simpson or his institution received grants/research
support from Amgen, Asubio Pharmaceuticals, Celgene,
Chugai, Galderma, Genentech, MedImmune, Regeneron
Pharmaceuticals, Inc, and Tioga; is a consultant for Galderma,
Genentech, MedImmune, and Regeneron Pharmaceuticals, Inc;
served on advisory boards for Celgene, Pfizer, and Valeant; and
served as a speaker for Anacor and Regeneron Pharmaceuticals,
Inc. Dr Bieber is an investigator and consultant for Regeneron
Pharmaceuticals, Inc; received honoraria, advisory board, or
consulting fees provided by Novartis, Astellas, and Atopix; and
received grant support from Astellas, Atopix, and MSD. Drs
Eckert and Pirozzi are employees of Sanofi and may hold stock
and/or stock options in the company. Drs Wu, Ardeleanu, and
Graham and Ms Mastey are employees and shareholders of
Regeneron Pharmaceuticals, Inc.
€
Data from this study were presented at the Osterreichische
Akademie der WissenschafteneInflammatory Skin Disease
Summit in Vienna, Austria, on November 19-21, 2014.
Accepted for publication October 22, 2015.
Reprint requests: Eric L. Simpson, MD, MCR, Department of
Dermatology (CH16D), Oregon Health and Science University,
3303 SW Bond Ave, Portland, OR 97239-4501. E-mail: simpsone@
ohsu.edu.
Published online January 14, 2016.
0190-9622
Ó 2015 by the American Academy of Dermatology, Inc. Published
by Elsevier, Inc. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).
http://dx.doi.org/10.1016/j.jaad.2015.10.043

491
492 Simpson et al J AM ACAD DERMATOL
MARCH 2016

Atopic dermatitis (AD) is an incurable, inflammatory Academy of Dermatology diagnostic criteria13;

skin disease characterized by skin barrier disruption chronic disease for 3 years or longer; Eczema Area
and immune dysregulation largely mediated by type 2 and Severity Index14 scores of 12 or higher at screening
1
helper T cells. Although AD onset generally occurs and 16 or higher at baseline; score 3 or higher
during early childhood, adult-onset disease is possible. (3 = moderate and 4 = severe) on the 0- to 4-point
Spontaneous remission may occur in late childhood, Investigator Global Assessment at screening and
but AD is a chronic, lifelong condition for many baseline; AD involvement covering 10% or more of
patients.2 body surface area at screening
The health and psychoso- and baseline; and docu-
CAPSULE SUMMARY
cial burden associated with mented recent history (within
AD has primarily been char- d The burden of atopic dermatitis has not 6 months before screening)
acterized in the pediatric been well characterized in adults. of inadequate response to
population.3-5 In adults, the outpatient treatment with
burden has been suggested
d Adults with moderate to severe atopic topical medications or pa-
to include the presence of dermatitis report a multidimensional tients for whom topical
other type 2 helper T-driven burden including sleep, quality-of-life, treatments were otherwise
comorbidities (asthma, aller- and psychosocial effects. inadvisable. Analyses of dis-
gies); daily effects associated d The patient-reported burden may not be ease burden were based on
with pruritus such as sleep captured by clinical outcome measures data collected at the screening
disturbance and functional that have been traditionally used to visit, before study interven-
impairment; and secondary evaluate atopic dermatitis. tions, and included all ran-
consequences including domized patients regardless
neuropsychiatric issues (anx- of randomization group.
iety, depression) and reduced health-related quality
of life (HRQoL).6-8 Although the importance of Patient-reported outcomes
capturing the full extent of this burden has been The clinical SCORing AD (SCORAD)15 index
9,10
recognized, comprehensive information on the includes 2 patient-reported outcomes, itch and sleep
patient burden in adults with moderate to severe AD assessment over the previous 3 days, measured using
is limited. The objective of this analysis was to a visual analog scale (VAS) (0 = no itch or sleep loss,
comprehensively evaluate the profile and overall 10 = worst imaginable itch or sleep loss).15 The
health burden of adult patients with moderate to pruritus numeric rating scale16 measures average and
severe AD, emphasizing patient-reported outcomes peak (worst) itch intensity for the previous 24 hours
in a prospective cohort. using an 11-point scale (0 = no itch to 10 = worst
imaginable itch). The 5-dimension (5-D) Pruritus
METHODS Scale17 (score range 5-25; higher scores indicate a
Study design greater negative impact of itch) assesses 5 dimen-
Data were from a multinational (Canada, the sions of itch (degree, duration, direction, disability,
Czech Republic, Germany, Hungary, Japan, and distribution) with a 2-week recall period. The
Poland, and the United States), dose-ranging, phase Patient-Oriented Eczema Measure (POEM)18
2b clinical trial of dupilumab. Dupilumab, a fully evaluates time spent in the past week with AD signs
human monoclonal antibody that targets the and symptoms (itch, bleeding, weeping/oozing
interleukin (IL)-4 receptor-a, blocks signaling of fluid, cracked skin, flaking skin, dry/rough skin)
IL-4 and IL-13, thereby reducing the signs and and their impact on sleep. POEM is scored on a
symptoms of AD.11 5-point scale (0 = no days to 4 = every day); score
Details of the study along with primary efficacy range is 0 to 28, and higher scores indicate greater
and safety results have been reported.12 All study severity. The Dermatology Life Quality Index
documents and procedures were approved by the (DLQI)19 is a 10-item questionnaire with Likert-type
appropriate institutional review boards/ethics com- responses to evaluate the impact of skin conditions
mittees at each study site. The study was registered on HRQoL over the past week (score range 0-30;
with ClinicalTrials.gov, number NCT01859988; higher scores indicate greater impact).
EudraCT number 2012-003651-11. In addition to the disease-specific patient-
reported outcomes, the generic 5-dimension
Patients EuroQol (EQ-5D)20 and the Hospital Anxiety and
Required for study inclusion were age 18 years or Depression Scale (HADS)21 were included. The
older; the presence of AD defined by American EQ-5D consists of 5 domains (mobility, self-care,
J AM ACAD DERMATOL Simpson et al 493
VOLUME 74, NUMBER 3

Table I. Demographic and clinical characteristics of

Abbreviations used:
the randomized patients at screening (N = 380)
AD: atopic dermatitis
DLQI: Dermatology Life Quality Index Variable Value
EQ-5D: 5-dimension EuroQol Age, y, mean (SD) 37.0 (12.2)
HADS: Hospital Anxiety and Depression Scale Sex, n (%)
HRQoL: health-related quality of life
IL: interleukin Male 234 (61.6)
POEM: Patient-Oriented Eczema Measure Female 146 (38.4)
SCORAD: SCORing Atopic Dermatitis Race, n (%)
VAS: visual analog scale Asian 82 (21.6)
Black or African American 34 (8.9)
White 257 (67.6)
usual activities, pain/discomfort, and anxiety/ Other 7 (1.8)
Disease duration, y*
depression) with 3 response levels (no problem,
Mean (SD) 27.6 (13.8)
some/moderate problems, or extreme problems/
Median (range) 27 (4-65)
unable to do) with ‘‘today’’ as the reference period, Age at diagnosis, n (%)
and a VAS health state thermometer (0 = worst health \5 y 156 (41.1)
to 100 = best health). Responses are used to generate 5-9 y 37 (9.7)
an overall health index ( 0.59 = worst health to 10-19 y 46 (12.1)
1 = best health); in the current analysis, United 20-29 y 56 (14.7)
Kingdomebased preferences were used to estimate 30-39 y 36 (9.5)
this index.22 The HADS consists of subscales for $40 y 49 (12.9)
anxiety and depression, each with 7 items and a BSA with AD involvementy
score range of 0 to 21; scores 7 or lower are Mean (SD) 47.6% (23.4)
Range 10%-99%
considered normal, 8 to 10 are borderline, and 11
Current atopic/allergic comorbidities, n (%)
or higher indicate clinical anxiety or depression.21
Asthma 153 (40.3)
Allergic rhinitis 195 (51.3)
Statistics Allergic conjunctivitis 92 (24.2)
Descriptive statistics were used throughout the Other allergies 230 (60.5)
analysis. Any systemic treatment for AD, n (%)
In the past year 183 (48.2)
Since AD onset 224 (58.9)
RESULTS Systemic corticosteroids, n (%)
The population (N = 380) was predominantly In the past year 137 (36.1)
male (61.6%), white (67.6%), and with a mean age of Since AD onset 188 (49.5)
37.0 (SD 12.2) years (Table I). The mean duration of EASI score, mean (SD) 29.2 (12.7)
AD was 27.6 years (SD 13.8), but some patients lived Total SCORAD score, mean (SD) 64.3 (13.1)
Total POEM score, mean (SD)z 20.4 (5.9)
with AD for up to 65 years. Although 41.1% of the
IGA score, mean (SD) 3.4 (0.5)
patients had AD since early childhood (age
IGA severity, n (%)
\5 years), the age at diagnosis was 20 years or Score = 3 [moderate] 243 (63.9)
older in 37.1% of patients (Table I). The mean Score = 4 [severe] 137 (36.1)
body surface area affected was approximately 50%
(range 10%-99%), and atopic comorbidities such as AD, Atopic dermatitis; BSA, body surface area; EASI, Eczema Area
asthma and allergic rhinitis were common (Table I). and Severity Index; IGA, Investigator Global Assessment; POEM,
Patient-Oriented Eczema Measure; SCORAD, SCORing Atopic
Scores for Investigator Global Assessment and POEM
Dermatitis.
were consistent with moderate to severe disease *n = 294.
(Table I). y
n = 379.
z
Nearly all patients (97.4%) used at least 1 topical n = 378.
treatment for their AD during the past 3 months,
primarily medium- to high-potency corticosteroids
alone or in combination with other topical agents On the pruritus numeric rating scale, mean scores
(94.5%) (data not shown). In addition, during the were the same for peak and average itch intensity
past year, almost half of the patients (48.2%) reported (6.5 [SD 2.1]) and the mean pruritus VAS component
using at least 1 systemic treatment for AD; systemic of SCORAD was 6.9 (SD 2.3) (Table II). Itch intensity
corticosteroids were used by 36.1% of patients and over the past 2 weeks on the 5-D Pruritus Scale was
cyclosporin by 12.9% (data not shown). rated as severe by 46.3% of patients and an additional
494 Simpson et al J AM ACAD DERMATOL
MARCH 2016

Table II. Patient-reported itch 1-4 5-7

Measure Value*
Pruritus NRS, mean (SD) n = 370
Average itch score 6.5 (2.1)
Worst itch score 6.5 (2.1)
SCORAD pruritus VAS, mean (SD) 6.9 (2.3)
Degree of itch from 5-D Pruritus Scale, n (%) n = 378
Unbearable 54 (14.2)
Severe 176 (46.3)
Moderate 132 (34.7)
Mild 16 (4.2)
Not present 0
Itch frequency per week from POEM, n (%) n = 378
Every day 326 (85.8) Fig 1. Atopic dermatitis. Frequency (days per week) of
5-6 d 23 (6.1) non-itch skin symptoms evaluated on the Patient-Oriented
3-4 d 19 (5.0) Eczema Measure. *Percentages were calculated with
1-2 d 9 (2.4) N = 380 as the denominator.
No days 1 (0.3)
Duration of itch from 5-D Pruritus Scale, n (%) n = 379
All day 113 (29.7)
18 to 24 h/d 45 (11.8)
12 to \18 h/d 81 (21.3)
6 to \12 h/d 69 (18.2)
\6 h/d 71 (18.7)

NRS, Numeric rating scale; POEM, Patient-Oriented Eczema

Measure; SCORAD, SCORing Atopic Dermatitis; VAS, visual analog
scale.
*Percentages were calculated with N = 380 as the denominator.

14.2% rated their itch as unbearable (Table II). The

majority (85.8%) of patients reported experiencing
itch every day of the week (POEM), and 41.5%
reported itching 18 h/d or more (5-D Pruritus Scale)
(Table II).
Nearly all patients also reported the frequent
occurrence of bleeding, oozing, cracking, flaking,
or drying of their skin (Fig 1). Most skin symptoms
occurred 5 d/wk or more in more than half the
patients, with dry or rough skin the symptom
reported most frequently by the highest proportion
of patients (91.1%) (Fig 1).
AD and itching had a substantial impact on
patient-reported sleep. On the 5-D Pruritus Scale,
68.2% of patients reported that itch delayed falling
asleep and occasionally or frequently woke them up
at night, and item 2 of POEM showed that 36.1%
reported that their sleep was disturbed every night
(Fig 2). Using a weighted average from the POEM
item, sleep was disrupted an average of 4.4 nights
over the previous week among all patients (data not
shown). On the SCORAD self-reported sleep loss
VAS, the mean score was 4.8 (SD 3.0) (data not
shown).
The mean HADS total score was 12.2 (SD 7.4), and
21.8% of patients had subscale scores for anxiety and
depression of 11 or higher, which is considered the
Fig 2. Atopic dermatitis. Impact of itch and atopic
dermatitis on sleep, assessed using items on the
5-dimension (5-D) Pruritus Scale and the Patient-
Oriented Eczema Measure (POEM ). *Percentages were
calculated with N = 380 as the denominator.
cut-off value for a clinical case of anxiety or
depression (Table III). In addition, 42.9% of patients
had scores 8 or higher, indicating at least possible
anxiety or depression. Anxiety symptoms were more
common than depression symptoms (Table III).
These proportions were consistent with the
anxiety/depression dimension of the EQ-5D; 42.9%
of patients reported being moderately anxious or
depressed and 7.9% were extremely anxious or
depressed (Table III).
The total DLQI score was 14.3 (SD 7.0) (data not
shown), consistent with a very large impact on
patients’ lives. Individual DLQI items showed that
substantial proportions of patients reported frequent
embarrassment or self-consciousness regarding their
appearance, and interference with participation in
relationships and daily life, including work/school
(Fig 3). Furthermore, item 7 on the DLQI specifically
J AM ACAD DERMATOL
VOLUME 74, NUMBER 3
Table III. Anxiety and depression
Anxiety and depression measure Value*
HADS score, mean (SD) n = 349
Total score 12.2 (7.4)
HADS-A score 7.0 (4.1)
HADS-D score 5.2 (4.0)
HADS thresholds, n (%)
HADS-A or HADS-D scores $11 83 (21.8)
HADS-A or HADS-D scores $8 163 (42.9)
HADS-A score $11 67 (17.6)
HADS-A score $8 146 (38.4)
HADS-D score $11 38 (10.0)
HADS-D score $8 92 (24.2)
EQ-5D, n (%) N = 380
Moderately anxious or depressed 163 (42.9)
Extremely anxious or depressed 30 (7.9)
EQ-5D, 5-Dimension EuroQol; HADS, Hospital Anxiety and
Depression Scale; HADS-A, Hospital Anxiety and Depression
Scale, anxiety subscale; HADS-D, Hospital Anxiety and
Depression Scale, depression subscale.
*Percentages were calculated with N = 380 as the denominator.
elicits information on prevention of work or study,
and 22.6% of patients reported that their skin
prevented them from working or studying over the
past week (data not shown). Among patients who
were not completely prevented from working/
studying, 19.2% reported that their skin had affected
their work or study ‘‘a lot’’ (data not shown).
Likewise, interference with these activities was
reported on item 4 of the 5-D Pruritus Scale; 46.0%
of patients reported that their itching ‘‘frequently’’ or
‘‘always’’ affected their work/study (Fig 4, A). Other
items on the 5-D Pruritus Scale relating to daily
function or participation were similarly reported to
be ‘‘frequently’’ or ‘‘always’’ affected by itch (Fig 4, A).
On the EQ-5D, the dimension most affected was
pain/discomfort; 76.8% of the patients reported
‘‘moderate’’ or ‘‘extreme’’ pain or discomfort (Fig 4,
B). In addition, 41.1% reported that they had ‘‘some
problems’’ or were ‘‘unable’’ to perform their usual
activities, and 50.8% reported ‘‘some problems’’ with
anxiety/depression. In contrast, most patients
reported ‘‘no problem’’ with mobility (83.9%) and
self-care (92.1%). The mean score on the EQ-5D VAS
was 60.0 (SD 22.9) and the overall health index score
was 0.659 (SD 0.305) (data not shown).
DISCUSSION
Results of this analysis provide insight into the
duration and dimensions of the patient burden
associated with AD in adults, showing that AD has
a profound negative impact on patients’ mental and
physical functioning, reducing their activity and
HRQoL. Notably, these patients had moderate to
Simpson et al 495
severe AD despite a high reliance on topical and
systemic treatments.
Although diagnosis occurred in early childhood in
most of the patients, the data indicate that AD is not
just a disease of childhood. Many of the patients had
been living with AD for nearly their entire lives,
including 50% of patients who had been living with
active disease for more than 27 years. Although
AD has often been thought to be a disease that
patients ‘‘grow out of,’’ these results and recent
longitudinal data suggest otherwise.3 Interestingly,
approximately 40% of these patients were given a
diagnosis of AD as adults, a proportion higher than
the 9% to 17% reported in the literature.23-25
Although age of diagnosis does not necessarily
indicate age of onset, these data nevertheless suggest
a need for further characterization of adult-onset AD.
Many of the patients were living with comorbid
asthma and other allergic or atopic conditions. Such
an association between AD and other atopic
conditions has been recognized,6,26 and the
presence of these conditions increases the disease
burden, health care use, and complexity of patient
management. Importantly, these comorbidities raise
the possibility that all these conditions have a similar
etiology driven by a common immune dysregulation
(eg, excess type 2 helper T inflammation), and it is
possible that a therapy with effects on comorbidities
and AD may provide additional clinical benefits.26
While skin symptoms including bleeding and
cracked or flaky skin were frequently reported, itch
was almost a constant presence, not only of duration,
with almost two thirds (62.9%) of patients reporting
itch 12 hours a day or more, but also of severity.
Notably, itch severity was consistent whether
measured using the pruritus numeric rating scale or
the VAS component of SCORAD. Pruritus resulted in
patient-reported sleep disturbances, consistent with
data from a study that objectively measured sleep
and showed that sleep disturbances were associated
with itch.27 Itch and difficulty sleeping have
previously been reported to be the most frequent
symptoms in adults with AD.28 Loss of sleep may
contribute to daytime sleepiness and fatigue, further
reducing functional activities and adversely affecting
mood and HRQoL because sleep likely has a
reciprocal relationship with mental health.29
The data also suggest that the mental health
effects of AD are substantial and may be under-
recognized. The current analysis shows that
anxiety or depressive symptoms are present in
approximately 43% of patients, similar to the 46%
of patients with AD identified as having probable
mood disorder in another study.30 In fact, approxi-
mately 22% of patients reported HADS scores
496 Simpson et al
Fig 3. Atopic dermatitis. Impact of skin condition on items contributing to health-related
quality of life as measured over the past week using the Dermatology Life Quality Index.
*Impact of treatment was for therapies before randomization to treatment with dupilumab or
placebo. yPercentages were calculated with N = 380 as the denominator.
A Leisure/social Housework/errands
Self-care
B activities discomfort
Fig 4. Atopic dermatitis. Patient-reported effects on
outcomes contributing to health-related quality of life:
functional and participatory activities assessed on the
5-D Pruritus Scale (N = 379) (A) and dimensions of the
5-dimension EuroQol (B). *Percentages were calculated
with N = 380 as the denominator.
clinically indicative of anxiety or depression, similar
to a European study that reported clinical depression
in 10.1% of patients with AD and clinical anxiety in
17.6%.8 Also consistent with previous observa-
tions,9,31 symptoms of anxiety were present in a
higher proportion of patients than were depressive
symptoms. This may reflect the psychological
distress produced by both the stigma associated
with visible AD skin lesions and the unpredictability
of disease flares, and may be manifested by the high
J AM ACAD DERMATOL
MARCH 2016
proportion of patients (61.6%) who reported being
embarrassed by or self-conscious of their skin
condition in this study. This psychological burden
can further negatively impact mood and HRQoL.30,32
Indeed, suicidal ideation has been reported in 15% of
patients in an AD population in Europe11 and up to
Work/study
20% of individuals with severe disease.33-36
Patient HRQoL appeared to be considerably
impaired, as assessed by both the DLQI and the
EQ-5D. When compared with other dermatologic
conditions, the mean DLQI score suggests that these
patients with moderate to severe AD reported a more
profound impact on HRQoL than patients with
psoriasis (8.8), pruritus (10.3), and chronic urticaria
depression
(9.9).37 Although the mean score on the DLQI (14.3)
for the study patients was midrange of the scale
(0-30), this score is slightly higher than the mean of
12.2 (range 4.5-21.4) that was reported across AD
studies in a review of the DLQI across dermatologic
conditions.37 It should also be noted, however, that
the more homogeneous population in the current
study contrasts with other studies, which often
consisted of pediatric and adult patients across
disease severity levels.
The EQ-5D VAS score of 60.0 suggests a lower
HRQoL than the 63.6 recently reported in a German
AD population,38 and may reflect the moderate to
severe AD inclusion criteria of the current study.
Furthermore, the EQ-5D overall health index score
of 0.659 is substantially lower than the normative
values of 0.856, 0.867, and 0.929 which have been
reported in United Kingdom, United States, and
Japanese populations, respectively,39 and lower
J AM ACAD DERMATOL
VOLUME 74, NUMBER 3
than that reported in the United States for other
symptomatic or chronic diseases, such as 0.834 for
psoriasis-type conditions and 0.751 for diabetes.40
The EQ-5D domain most affected was pain/
discomfort. Although pain is not typically reported
as a key issue in AD, the presence of overlapping
mechanisms between pain and itch,41 and the
constancy of the reported itch in these patients,
which could potentially result in neuroplastic change
over time, suggests that further investigation into the
relationship between itch and pain in AD may be
warranted.
Limitations of this study include generalizability;
conclusions may not necessarily apply to patients
with mild disease or patients unwilling to participate
in a clinical trial. In addition, this was an international
study so we cannot exclude cultural differences that
may have influenced responses to the patient-
reported outcomes. Nevertheless, we used validated
instruments that were translated into the appropriate
languages for the countries in the study. Similarly,
our use of the United Kingdom algorithm for
estimating the EQ-5D may limit interpretability.
Although the DLQI is specific for dermatologic
conditions, the EQ-5D is generic and, therefore, it
is possible that at least part of the reduction in
HRQoL observed with this measure was a result of
other comorbid conditions, such as asthma.
Overall, this comprehensive analysis provides a
novel perspective on the multidimensional nature
of the patient burden of moderate to severe AD in
adults, of whom a substantial proportion were given
a diagnosis as adults, indicating that AD is not only a
disease of early childhood. This burden is manifested
by patient-reported symptoms, comorbid conditions
including a high rate of anxiety/depression, an
apparent ineffective and potentially harmful
medication burden, and lower HRQoL than in other
dermatologic conditions. This burden, combined
with the substantial proportion of patients requiring
systemic corticosteroid therapy, a treatment discour-
aged by current treatment guidelines, highlights the
need for novel therapeutics for this patient
population. Management strategies should include
more effective therapies directed at the underlying
pathophysiology, the range of symptoms, and
comorbid conditions, and should incorporate mental
health support.
The authors would like to thank the patients who
participated in the study; the co-investigators and staff at
the participating centers; and Steven P. Weinstein, MD,
PhD (Regeneron Pharmaceuticals, Inc), and E. Rand
Sutherland, MD (Sanofi), for their critical review and
discussions of the manuscript.
Simpson et al 497
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