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ORIGINAL RESEARCH
Treatment Patterns and Healthcare Resource
Utilization Among Patients with Atopic Dermatitis:
A Retrospective Cohort Study Using German Health
Claims Data
Marie Schild .Valeria Weber .Diamant Thac¸i .Agnes Kisser .
Wolfgang Galetzka .Dirk Enders .Franziska Zu
¨gel .Christoph Ohlmeier .
Holger Gothe
Received: March 21, 2022 / Accepted: July 4, 2022 / Published online: July 24, 2022
ÓThe Author(s) 2022
ABSTRACT
Introduction: Atopic dermatitis (AD) is a com-
mon inflammatory skin disease. Many patients
are initiating a systemic therapy, if the disease is
not adequately controlled with topical treat-
ment only. Currently, there is little real-world
evidence on the AD-related medical care situa-
tion in Germany. This study analyzed patient
characteristics, treatment patterns, healthcare
resource utilization and costs associated with
systemically treated AD for the German
healthcare system.
Methods: In this descriptive, retrospective
cohort study, aggregated anonymized German
health claims data from the InGef research
database were used. Within a representative
sample of four million insured individuals,
patients with AD and systemic drug therapy
initiation (SDTI) in the index year 2017 were
identified and included into the study cohort.
Systemic drug therapy included dupilumab,
systemic corticosteroids (SCS) and systemic
immunosuppressants (SIS). Patients were
observed for one year starting from the date of
SDTI in 2017.
Results: 9975 patients were included (57.8%
female, mean age 39.6 years [SD 25.5]). In the
one-year observation period, the most common
systemic drug therapy was SCS ([99.0%).
Administrations of dupilumab (0.3%) or dis-
pensations of SIS were rare (cyclosporine: 0.5%,
azathioprine: 0.6%, methotrexate: 0.1%). Med-
ian treatment duration of SCS, cyclosporine and
Marie Schild and Valeria Weber contributed equally to
this work.
Supplementary Information The online version
contains supplementary material available at https://
doi.org/10.1007/s13555-022-00773-3.
M. Schild A. Kisser F. Zu
¨gel
Pfizer in Germany, Linkstraße 10, 10785 Berlin,
Germany
V. Weber C. Ohlmeier H. Gothe (&)
IGES Institut GmbH, Friedrichstr. 180, 10117 Berlin,
Germany
e-mail: holger.gothe@iges.com
D. Thac¸i
Institute and Comprehensive Center for
Inflammation Medicine, University of Luebeck,
Ratzeburger Allee 160, 23538 Luebeck, Germany
W. Galetzka D. Enders
InGef-Institute for Applied Health Research Berlin
GmbH, Spittelmarkt 12, 10117 Berlin, Germany
H. Gothe
Department of Health Sciences/Public Health,
Medical Faculty, TU Dresden, Fetscherstraße 74,
01307 Dresden, Germany
H. Gothe
Department of Public Health, Health Services
Research and HTA, UMIT, Eduard-Wallno
¨fer-
Zentrum 1, 6060 Hall in Tirol, Austria
Dermatol Ther (Heidelb) (2022) 12:1925–1945
https://doi.org/10.1007/s13555-022-00773-3
azathioprine was 27 days, 102 days, and
109 days, respectively. 2.8% of the patients
received phototherapy; 41.6% used topical cor-
ticosteroids and/or topical calcineurin inhi-
bitor. Average annual costs for medications
amounted to €1237 per patient. Outpatient
services were used by 99.6% with associated
mean annual costs of €943; 25.4% had at least
one hospitalization (mean annual costs: €
5836). 5.3% of adult patients received sickness
benefits with associated mean annual costs of €
5026.
Conclusions: Despite unfavorable risk–benefit
profile, this study demonstrated a common
treatment with SCS, whereas other systemic
drug therapy options were rarely used. Further-
more, the results suggest a substantial economic
burden for patients with AD and SDTI.
Keywords: Claims data analysis;
Corticosteroids; Costs; Dermatitis; Atopic;
Germany; Healthcare resource utilization
Key Summary Points
Why carry out this study?
Patients with atopic dermatitis (AD) who
are more severely affected and who
cannot manage their disease with topical
anti-inflammatory drugs require systemic
therapy.
Treatment patterns of systemic drug use
(systemic corticosteroids, systemic
immunosuppressants, and dupilumab),
healthcare resource utilization and
associated costs in patients with AD and
systemic drug therapy initiation
(aged C2 years) have not sufficiently
been investigated under routine care
conditions in Germany.
What was learned from this study?
Despite unfavorable risk–benefit profile,
treatment with systemic corticosteroids
was common (even in non-adults),
whereas other systemic drug therapy
options were rarely used.
Considering the observed treatment
duration within this study, the use of
systemic corticosteroids in most cases was
no longer in line with European guideline
recommendations.
AD treated with systemic drugs resulted in
substantial direct (€3677 per patient per
year) and indirect costs due to AD (€6235
per adult patient per year) in Germany.
INTRODUCTION
Atopic dermatitis (AD) is a common inflamma-
tory skin disease characterized by pruritus,
eczematous lesions, and its chronically relaps-
ing course. For European countries, a prevalence
of 4.4% was estimated among adults based on
survey data from 2016 [1]. In Germany,
approximately 13% of children and adolescents
aged 0–17 years are at least temporarily affected
by AD [2]. Patients with AD often suffer from
other allergic diseases, such as bronchial asthma
and allergic rhinitis [3,4], as well as psycho-
logical disorders, particularly depression [5–7].
The disease presents clinically in heterogeneous
ways and is characterized by an alternating
occurrence of acute flares followed by mild
intervals [8]. If inadequately controlled, AD can
lead to a reduced health-related quality of life in
adults and children [6,9].
Adequate disease control can be achieved by
using disease activity-adapted treatment
options in a step-wise manner according to the
individuals’ disease severity level (mild, mod-
erate, and severe). Therapy options can be cat-
egorized into continuous and intermittent
therapy. European guidelines recommend long-
term non-pharmacological topical treatments
(e.g., emollients and baths) as basic therapy and
the avoidance of provocative factors [10].
Topical anti-inflammatory drugs such as
topical corticosteroids (TCS) and/or topical cal-
cineurin inhibitors (TCI) can be used temporarily
or, according to current guideline recommen-
dations, as proactive treatment depending on the
disease severity [10]. For patients more severely
affected and suffering from frequent flares,
1926 Dermatol Ther (Heidelb) (2022) 12:1925–1945
treatment can be intensified by using pho-
totherapy (recommended for adults only), sys-
temic immunosuppressive agents (SIS) such as
cyclosporine (in-label), or systemic corticos-
teroids (SCS). The use of SCS can be considered in
the treatment of acute flares or in conjunction
with a therapy concept for the subsequent treat-
ment in patients with severe disease progression
according to current German and European
guideline recommendations [11,12]. The SIS,
azathioprine, mycophenolate mofetil, and
methotrexate (MTX), can be used as an off-label
treatment in patients with severe AD [11].
Cyclosporine, off-label products, and SIS are only
suitable for limited time intervals. One suit-
able long-term treatment option is the mono-
clonal antibody dupilumab, for which various
studies have confirmed a favorable safety profile
across all age groups, including children from the
age of 6 years and elderly patients [13–17].
Dupilumab is approved and fully reimbursed for
the treatment of moderate-severe AD in adults
and adolescents aged 12 years and older, who are
not adequately controlled with a single use of
topical medications, since September 2017
[11,12]. Since November 2020, it has also been
approved for the treatment of severe AD in chil-
dren aged 6–11 years. With baricitinib, tralok-
inumab, upadacitinib and abrocitinib, further
systemic drug therapy options have been
approved for the treatment of moderate-severe
AD in adults in Germany since October 2020,
June 2021, August 2021 and December 2021.
Several studies were published on the costs of
AD in Germany [18–24]. Some of them reported
direct and indirect costs for both children and
adults [21,23]. The most recent study was
published in 2005 and found average annual
total costs of €1425 per patient (both children
and adults) with AD [21]. As the medical care
situation in AD has changed since then, more
recent data on the costs of AD are needed.
Currently, there are few studies investigating
the recent medical care situation and resource
utilization of patients with AD undergoing sys-
temic drug therapy in the German healthcare
context. This study aims to (1) characterize
patients with AD and systemic drug therapy
initiation (SDTI) regarding their demographics
and diagnosed comorbidities and (2) to describe
current treatment patterns, (3) healthcare
resource utilization (HCRU), and associated
costs in this patient population.
METHODS
Data source
The data source of the present study was the
InGef (Institute for Applied Health Research
Berlin) research database. The anonymized
database contains longitudinal claims data from
approximately seven million individuals who are
insured with one of more than 58 German
statutory health insurance (SHI) companies
included in this database. For the purpose of this
analysis, an aggregated anonymized sample of
approximately four million insured persons was
used which can be considered representative of
the German population regarding age and sex
[25]. The InGef research database includes
sociodemographic information such as sex, age,
and region of residence. In addition, detailed
information on hospitalizations, outpatient
physician contacts and outpatient drug pre-
scriptions can be obtained from the database.
Inpatient data comprises the date of admission,
date of discharge, the reason for discharge, diag-
nostic and therapeutic information with exact
dates, and diagnoses. Diagnoses can be differen-
tiated between hospital main discharge diag-
noses and secondary diagnoses. Outpatient data
also includes diagnostic and therapeutic infor-
mation with exact dates. Inpatient and outpa-
tient diagnoses are recorded through the coding
according to the German Modification of the
International Classification of Diseases, 10th
Revision (ICD-10-GM). Outpatient prescription
data of reimbursed drugs includes information
on the date of prescription and dispensation as
well as the pharmaceutical reference number.
Based on a pharmaceutical reference database,
information on the Anatomical Therapeutical
Chemical code (ATC code), the defined daily
dose (DDD), the packaging size, as well as the
strength and formulation of the drug can be
linked for each prescribed drug.
Since all patient-level data in the database
are anonymized to comply with German data
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1927
protections regulations and German federal law,
approval of an Ethics Committee was not
required. The research was conducted in accor-
dance with the Declaration of Helsinki.
Study design
A retrospective cohort study was conducted
based on German claims data from January 01,
2016 until December 31, 2018. Patients with a
documented AD diagnosis were included into
the study cohort if they had SDTI between
January 01, 2017 and December 31, 2017 (index
period). SDTI was defined as the first docu-
mented health claim for systemic medication
during the index period (index date) after a
baseline period of 1 year without a respective
claim. An observation period of 1 year after the
index was used to assess the research question.
The study was of descriptive nature only;
thus, no hypotheses were specified in advance
and no sample size calculation was carried out.
Inclusion and exclusion criteria
Insured individuals were included into the
study cohort, if they fulfilled all of the following
criteria:
1. They were at least 2 years old at the end of
the index period.
2. They had at least one documented diagno-
sis (hospital discharge diagnosis or con-
firmed outpatient diagnosis) of AD (ICD-
10-GM: L20.8, L20.9) within the index
period.
3. They had at least one health claim for
systemic drug therapy (i.e., dupilumab,
SCS or SIS) during the index period. The
index date was defined as the first observ-
able outpatient dispensation or inpatient
administration of at least one systemic drug
(see Table S2 in the electronic supplemen-
tary material for details) between January
01, 2017 and December 31, 2017.
4. They were continuously insured during the
baseline period.
5. They were continuously insured during the
observation period or until death.
6. They had a documented AD diagnosis at the
index date or during the baseline period.
Insured individuals were excluded from the
cohort if they did not fulfill the aforementioned
inclusion criteria. Furthermore, missing infor-
mation on year of birth and sex led to an
exclusion. Since the present analysis focused on
patients with SDTI, patients with AD and a
documented health claim for systemic drug
therapy during the baseline period were exclu-
ded from the analysis.
Assessment of patient characteristics
Patient characteristics were assessed during the
post-index observation period. Socio-demo-
graphic variables included age and sex. To
ascertain the comorbidity burden, main or sec-
ondary inpatient discharge diagnoses, and
confirmed outpatient diagnoses were taken into
account. The documentation of one of these
diagnosis types was sufficient for identification.
To describe the general comorbidity burden, the
Elixhauser Comorbidity Score (ECS) comprising
31 single diseases (see Table S1 in the electronic
supplementary material for details) was used
[26–28]. Furthermore, the specific comorbidity
burden was evaluated by a data-driven approach
identifying the top-10 most frequent
comorbidities.
Assessment of treatment patterns
Information on systemic drug therapy, con-
comitant topical medication (TCS, TCI), and
other AD-related medication (excl. systemic
drugs) were identified based on outpatient drug
dispensations and, in the case of dupilumab, on
inpatient administered drugs. Systemic medi-
cation was evaluated at the index date and
during the observation period; whereas the
assessment of concomitant treatment with TCS
and/or TCI was based on the observation period
only.
The use of concomitant TCI and/or TCS was
analyzed considering the following categories:
‘‘receiving TCS while not receiving TCI’’, ‘‘re-
ceiving TCI while not receiving TCS’’, ‘‘not
1928 Dermatol Ther (Heidelb) (2022) 12:1925–1945
receiving TCS or TCI’’, and ‘‘receiving TCS and
TCI’’. The latter category does not necessarily
imply the simultaneous use of both drug classes.
Patients in this category did only receive at least
one dispensation of each drug class within the
1-year observation period.
The operationalization of other AD-related
medication is listed in Table S4 (see electronic
supplementary material).
Drug therapy was classified by three- or four-
digit level of the ATC code; specific drugs were
classified by seven-digit level of the ATC code
(see Tables S2, S3, and S4 in the electronic
supplementary material for details). In the case
of dupilumab, the corresponding OPS (German
procedure classification) code was included in
addition to the ATC code. Furthermore, the
prescribed defined daily doses (DDD) and
accumulated costs (pharmacy retail price) dur-
ing the observation period were ascertained.
The persistence of systemic drug therapy was
analyzed based on treatment discontinuation
and switching behavior. To calculate the range
and to define the run-out date of a prescription
of systemic drugs, the package size was multi-
plied by the active ingredient content per tablet
or the unit of other application forms and
divided by the DDD of the active ingredient.
Discontinuation of therapy was defined as a gap
of [90 days between the run-out date of a sys-
temic drug and any subsequent prescription for
the respective drug therapy. If the drug therapy
was discontinued, the run-out date of the last
dispensation was defined as the date of discon-
tinuation. Switching was determined if a dis-
pensation of another systemic drug therapy was
documented within the supply period of the
initial systemic drug therapy or during the
90-day period after the run-out date of the sys-
temic drug therapy.
Assessment of HCRU and associated costs
HCRU and associated costs were determined
both overall as well as due to AD. All analyzes
were based on the 1-year post-index observation
period. Analysis of all-cause HCRU included:
hospitalizations, outpatient physician contacts,
overall prescription medication, and sick leave.
Assessment of HCRU due to AD included: hos-
pitalizations due to AD (main discharge diag-
nosis of AD), outpatient phototherapy, AD-
related medication, and sick leave due to AD.
At least one health claim of a respective ser-
vice was sufficient to meet the criterion. For
each healthcare service, relative frequencies and
the mean number of utilized services were
ascertained. Concerning hospitalizations and
sick leave, mean duration was also assessed.
Total costs to the SHI and mean annual costs
per patient were calculated for the respective
healthcare service. All-cause direct costs com-
prised the following categories: outpatient
costs, hospitalization costs, and overall pre-
scription medication costs. Direct costs due to
AD included outpatient phototherapy costs,
costs for hospitalizations due to AD, and AD-
related prescription medication costs. All-cause
indirect costs and indirect costs due to AD were
evaluated based on costs for sickness benefits
(all-cause) and sickness benefits due to AD,
respectively.
Health services that are paid for privately,
such as over-the-counter (OTC) drugs, are not
included in German claims data. Since OTC
medication was not comprised in the database,
associated out-of-pocket costs could not be
analyzed.
Statistical analyses
The age was categorized into clinically relevant
categories: 2–11 years, 12–17 years,
and C18 years. Furthermore, the ECS was cat-
egorized into the following categories: 0 dis-
eases, 1 disease, 2 diseases, 3 diseases, 4 diseases,
5 diseases, and C6 diseases.
Patient characteristics were stratified by sex,
with comorbidities also stratified by age. Anal-
yses concerning treatment patterns, HCRU and
associated costs were carried out stratified by
age. For categorical variables, frequencies and
percentages were ascertained. For continuous
variables, means, standard deviations (SD), and
medians were calculated.
The proportion of patients with a specific
comorbidity, use of medication or healthcare
service was calculated by dividing the number
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1929
of patients fulfilling the respective criteria by
the number of patients in the study cohort.
Mean annual costs of healthcare services
were calculated by dividing the sum of costs by
the number of patients receiving the respective
health service during the observation period.
Costs were analyzed descriptively. A more
comprehensive analysis of the economic bur-
den of the disease was not subject of this study.
Persistence of the index systemic drug ther-
apy was described using Kaplan–Meier rates.
The defined outcome was discontinuation of
index systemic drug therapy. Treatment dis-
continuation was analyzed in days, based on
the duration of treatment from the start date to
the date of discontinuation or until the end of
the 1-year observation period. Patients with no
observed discontinuation of index systemic
drug therapy or an ending of the insurance
period during the obseravtion period were cen-
sored. The Kaplan Meier analysis was carried out
separately for each drug/drug class as well as for
the overall patient cohort.
All statistical analyses were of descriptive
nature only. Data management and analyses
were performed with the statistical software R
(Version: Microsoft R Open 3.5.0).
RESULTS
Patient characteristics
Among the representative InGef sample in 2017
(n= 4,332,845), 3,940,142 insured individuals
were continuously observable until the end of
2017 or until death. Of those, 3.7% had a
prevalent AD diagnosis (n= 158,673). Of the
latter, 10.6% received systemic medication
(n= 16,548). Based on the aforementioned
selection criteria, a total of 9975 patients with
AD and SDTI were included in the study cohort
(Fig. 1).
Patient characteristics are presented in
Table 1. The mean age within the study cohort
was 39.6 years (SD 25.5) with male patients
having a lower mean age (34.8 years, SD 27.0)
compared to female patients (43.0 years, SD
23.7). Females were slightly overrepresented in
the study cohort (57.8%). 26.7% of the patients
were under 18 years old with 22.5% and 4.2%
being in the age of 2–11 and 12–17 years,
respectively. 38.1% of the male patients were
under 18 years of age, whereas only 18.3% of
the female patients were younger than 18 years.
The mean number of diseases on the ECS was
2.3 (SD 2.5); 10.6% of the patients within the
study cohort (female: 10.8%; male: 10.4%)
showed at least 6 diseases. Females showed a
higher general comorbidity burden in compar-
ison with males. Overall, back pain (34.7%),
acute upper respiratory infections (32.3%) and
bronchial asthma (31.5%) were the most fre-
quently observed comorbidities. Figure 2
depicts the most frequent comorbidities of the
studied population stratified by age.
Treatment patterns of systemic drug use
The distribution of the index systemic drug
therapy is depicted in Table S5 (see electronic
supplementary material). At index, 99.0%,
0.4%, 0.3%, and 0.2% received dispensations of
glucocorticoids, fixed-dose combinations of
corticosteroids, cyclosporine and azathioprine,
respectively. 0.1% of the patients received
combined azathioprine and glucocorticoids. No
cases, or fewer than five cases, were observed
with dispensations of dupilumab, methotrex-
ate, or other combinations.
In the observation period, SCS were the most
frequently observed dispensed drugs. 99.2% of
the patients received at least one dispensation
of glucocorticoids and 0.5% at least one dis-
pensation of fixed-dose combinations of corti-
costeroids (Table 2). Patients with dispensations
of SIS such as cyclosporine (0.5%), azathioprine
(0.6%) or methotrexate (0.1%) were rarely
observed. Dupilumab was dispensed to a share
of 0.3% of the patients. Stratifying by age, a
similar distribution was observed and patients
with dispensations of SCS were overrepresented
in every age group.
As shown in Table 2, mean dispensed DDD
of glucocorticoids were with 84.8 higher in the
adult age group in comparison with younger
age groups during the 1-year observation period
(2–11 years: 10.0 mean DDD, 12–17 years: 45.2
mean DDD). In contrast, the intensity of
1930 Dermatol Ther (Heidelb) (2022) 12:1925–1945
systemic drug therapy with azathioprine was
with 218.1 mean DDD higher in the age group
of 12–17 years in comparison with the age
group of C18 years (118.2 mean DDD).
A share of 2.8% of patients received at least
one prescription for phototherapy. Prescrip-
tions for phototherapy were observed within
adult (3.8%) and non-adult patients (2–11 years:
0.0%, 12–17 years: 1.2%).
Persistence of systemic drug therapy
During the 1-year observation period, discon-
tinuation of index systemic drug therapy was
most frequent within patients treated with SCS
(96.9%) followed by patients treated with SIS,
such as cyclosporine (76.0%) and azathioprine
(63.6%) (Table 3). Therapy with SCS lasted on
average 46.3 days (SD 58.4) and with azathio-
prine 85.0 days (SD 85.6) whereas treatment
with cyclosporine lasted on average 119.3 days
(SD 104.4).
Figure 3illustrates the time until discontin-
uation for each systemic treatment group.
Overall (n= 9963), persistence was 35% and
19% after 45 days and 90 days. The subgroups
differed substantially in size (SCS: n= 9912,
cyclosporine: n= 25, azathioprine: n= 22). In
the largest subgroup of patients treated with
SCS, the probability of remaining under the
index systemic treatment was 34% and 18%
after 45 days and 90 days. After 1 week, the
probability of being treated with SCS was 80%.
Persistence in the cyclosporine subgroup was
76% and 52% after 45 days and 90 days, in the
subgroup of patients treated with azathioprine
Fig. 1 Patient selection in year 2017. AD Atopic Dermatitis, ICD International Classification of Diseases, ATC Anatomical
Therapeutical Chemical
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1931
Table 1 Demographic characteristics and comorbidity of patients with AD and SDTI in the 1-year observation period
Female (n= 5762) Male (n= 4213) All (n= 9975)
n%n%n%
Age (years)
2–11 846 14.7 1397 33.2 2243 22.5
12–17 210 3.6 207 4.9 417 4.2
18–29 695 12.1 373 8.9 1068 10.7
30–39 619 10.7 309 7.3 928 9.3
40–49 811 14.1 406 9.6 1217 12.2
50–59 1029 17.9 584 13.9 1613 16.2
60–69 755 13.1 407 9.7 1162 11.6
70–79 491 8.5 336 8.0 827 8.3
C80 306 5.3 194 4.6 500 5.0
All 5762 100.0 4213 100.0 9975 100.0
Mean (SD) 43 23.7 34.8 27.0 39.6 25.5
Sex
Female 5762 57.8
Male 4213 42.2
General comorbidity (ESC)
0 diseases 1205 20.9 1183 28.1 2388 23.9
1 disease 1341 23.3 1281 30.4 2622 26.3
2 diseases 1065 18.5 565 13.4 1630 16.3
3 diseases 725 12.6 337 8.0 1062 10.6
4 diseases 477 8.3 226 5.4 703 7.0
5 diseases 327 5.7 183 4.3 510 5.1
C6 diseases 622 10.8 438 10.4 1060 10.6
Mean (SD) 2.5 (2.5) 2.1 (2.5) 2.3 (2.5)
Q1, Q3 1.0 3.0 0.0 3.0 1.0 3.0
Median 2.0 1.0 1.0
Min, Max 0.0 19.0 0.0 18.0 0.0 19.0
Specific comorbidity (top 10)
Back pain 2314 40.2 1149 27.3 3463 34.7
Acute upper respiratory infections 1754 30.4 1472 34.9 3226 32.3
Bronchial asthma 1822 31.6 1321 31.4 3143 31.5
Hypertension 1816 31.5 1197 28.4 3013 30.2
1932 Dermatol Ther (Heidelb) (2022) 12:1925–1945
59% and 45% after 45 days and 90 days,
respectively. Median treatment duration was
27 days in the SCS-subgroup, 102 days in the
cyclosporine and 109 days in the azathioprine
subgroup. Since none or fewer than five patients
were identified initiating dupilumab or
methotrexate treatment at the index, no data
were available regarding treatment duration for
this patient group.
Within the 1-year observation period, only a
few switches could be observed. 51 patients
(0.5%) were found to have switches to any other
systemic drug therapy (Table 6).
Concomitant topical drug therapy (TCS
and/or TCI)
58.4% of the patients neither received TCS nor
TCI (Table 4). Within patients receiving dis-
pensations of concomitant TCS and/or TCI, TCS
was the most frequently dispensed drug class
(34.5%). TCI was dispensed in 1.8% of the
Table 1 continued
Female (n= 5762) Male (n= 4213) All (n= 9975)
n%n%n%
Vasomotor and allergic rhinitis 1727 30.0 1211 28.7 2938 29.5
Disorders of refraction and accommodation 1813 31.5 1116 26.5 2929 29.4
Other and unspecified dermatitis 1447 25.1 984 23.4 2431 24.4
Disorders of lipoprotein metabolism and other lipidemias 1282 22.2 848 20.1 2130 21.4
Somatoform disorders 1266 22.0 465 11.0 1731 17.4
Acute bronchitis * * 843 20.0 1670 16.7
ESC Elixhauser Comorbidity Score, SD standard deviation, Qquartile
*
Not among the top 30 within this stratum
Fig. 2 Specific comorbidity (top 10), in the 1-year observation period, stratified by age
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1933
patients; 5.3% received dispensations of both
TCI and TCS.
Stratifying by age, dispensations of con-
comitant TCS treatment were more frequent in
the adult age group (37.3%) compared to the
non-adult age groups (2–11 years: 26.8%,
12–17 years: 26.9%). However, the share of
patients aged 12–17 years and being dispensed
TCI was higher (2.6%) in comparison with adult
patients (1.9%) and those aged 2–11 years
(1.4%). Dispensations of both TCI and TCS were
more frequently observed in the age group of
Table 2 Use of systemic therapy (incl. phototherapy) during the 1-year observation period, stratified by age
2–11 years
(n= 2243)
12–17 years
(n= 417)
‡18 years
(n= 7315)
All (n= 9975)
n%Mean
DDD
n% Mean
DDD
n% Mean
DDD
n% Mean
DDD
Systemic drug therapy
Glucocorticoids 2241 99.9 10.0 412 98.8 45.2 7245 99.0 84.8 9898 99.2 66.2
Azathioprine 5 0.2 83.3 6 1.4 218.1 49 0.7 118.2 60 0.6 125.3
Cyclosporine \5– – \5 – – 45 0.6 95.1 51 0.5 93.9
Dupilumab \5– – \5 – – 26 0.4 212.1 28 0.3 205.1
Methotrexate – – – \5– – \5 – – 5 0.1 72.0
Corticosteroids, fixed-dose
combinations
– – – – – – 45 0.6 19.4 45 0.5 19.4
Phototherapy* 0 0.0 5 1.2 277 3.8 282 2.8
Numbers which are too low or might allow indirect calculability of too low case numbers cannot be displayed due to data
protection reasons
DDD defined daily dose, SD standard deviation,
*Including all patients, who received prescriptions for outpatient and inpatient phototherapy
Table 3 Time until discontinuation of index systemic drug therapy during the 1-year observation period (n= 9975),
90 days gap allowed
nDiscontinuous users Time to discontinuation
n% Mean SD
Index systemic drug therapy
Glucocorticoids, corticosteroids for systemic use 9912 9605 96.9 46.3 58.4
Cyclosporine 25 19 76.0 119.3 104.4
Azathioprine 22 14 63.6 85.0 85.6
Methotrexate \5– – – –
All 9963 9657 96.9 46.8 59.2
Numbers which are too low or might allow indirect calculability of too low case numbers cannot be displayed due to data
protection reasons
SD standard deviation
1934 Dermatol Ther (Heidelb) (2022) 12:1925–1945
12–17 years compared to other age groups (2–-
11 years: 3.5%, C18 years: 5.8%).
Within the adult age group, mean dis-
pensed DDD of TCS were notably higher (109.4
mean DDD, SD 167.2) compared to the younger
age groups (2–11 years: 40.7 mean DDD, SD
55.5; 12–17 years: 59.3 mean DDD, SD 68.3). In
contrast, mean DDD of TCI were higher within
non-adult patients (2–11 years: 25.9 mean DDD,
SD 32.3, 12–17 years: 29.3 mean DDD, SD 43.1)
compared to adult patients (22.9 mean DDD, SD
24.0).
HCRU and associated costs
HCRU and associated costs are presented in
Tables 5and 6.
Mean annual costs per patient for drug
treatment were €1237. Ninety-nine percent of
the patients were observed with at least one
Fig. 3 Time until discontinuation of index systemic drug therapy, Kaplan–Meier curve
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1935
outpatient physician visit with on average 26.4
contacts per patient in the observation period.
Outpatient services were associated with mean
annual costs per patient of €943. 2.3% of the
patients had at least one documented outpa-
tient visit for phototherapy associated with
mean annual costs of €101.
In the study cohort, 25.4% of the patients
were observed with at least one hospitalization.
Patients had on average 1.7 admissions (SD 1.6)
with a mean duration of 13.0 days (SD 21.7).
Associated mean annual costs per patient
amounted to €5836. At least one hospitaliza-
tion due to AD was observed in 0.9% of the
patients (mean number of admissions: 1.2 [SD
0.6], mean duration: 13.7 days [SD 15.3]).
Associated mean annual costs per patient
amounted to €3455.
During the observation period, 43.2% of the
adult patients in the study cohort were observed
with having at least one documented sick leave
due to any cause. Adults had on average 2.8 sick
leaves (SD 2.2) with a mean duration of
33.5 days (SD 49.1). Sick leave due to AD in
particular was observed within 3.3% of the
patients. Those had on average 1.2 sick leaves
due to AD with an average duration of 24.0 days
(SD 48.7).
Claims for sickness benefits were observed in
5.6% (n= 341) of the adult patients. Associated
mean annual costs per patient amounted to €
5026. Sickness benefits due to AD were observed
in 0.4% (n= 22) of the adult patients (mean
annual costs per adult patient: €6235).
Summed up, all-cause direct and indirect
costs were €8016 and €5026 per (adult) patient
per year among patients with AD and SDTI,
respectively. The direct and indirect annual
costs per (adult) patient due to AD amounted to
€3677 and €6235, respectively.
DISCUSSION
Summary of findings
The aim of this study was to describe current
treatment patterns, HCRU and costs associated
with managing patients with AD and SDTI in
Germany. Based on data of a German health
insurance database, 9975 (0.2%) patients with
AD and SDTI were identified within the year
2017. Most of the patients with AD and SDTI
([99.0%) used SCS as systemic medication;
whereas use of SIS (azathioprine, cyclosporine,
and methotrexate) and dupilumab was rare
(each \1%). Treatment duration for SCS,
cyclosporine and azathioprine was 27 days,
102 days, and 109 days, respectively. Analysis of
HCRU showed that 25.4% of the patients with
AD and SDTI had at least one hospitalization
whereas 0.9% had at least one admission due to
AD. 43.2% had at least one sick leave and 3.3%
had at least one sick leave due to AD. Among
Table 4 Use of concomitant TCS and/or TCI during the 1-year observation period, stratified by age
2–11 years (n= 2243) 12–17 years (n= 417) ‡18 years (n= 7315) All (n= 9975)
n% Mean
DDD
SD n% Mean
DDD
SD n% Mean
DDD
SD n% Mean
DDD
SD
Concomitant topical therapy
Neither TCI
nor TCS
1532 68.3 266 63.8 4024 55.0 5822 58.4
TCS only 602 26.8 40.7 55.5 112 26.9 59.3 68.3 2732 37.3 109.4 167.2 3446 34.5 95.8 153.5
TCI only 31 1.4 25.9 32.3 11 2.6 29.3 43.1 137 1.9 22.9 24.0 179 1.8 23.8 26.9
TCI and TCS
TCI 78 3.5 37.8 59.7 28 6.7 42.5 51.4 422 5.8 33.7 46.4 528 5.3 34.7 48.8
TCS 78 3.5 96.6 144.1 28 6.7 246.1 338.3 422 5.8 156.3 276.0 528 5.3 152.3 265.9
DDD defined daily dose, TCI topical calcineurin inhibitor, TCS topical corticosteroids, SD standard deviation
1936 Dermatol Ther (Heidelb) (2022) 12:1925–1945
Table 5 Healthcare resource utilization during the 1-year observation period, stratified by age
2–11 years (n= 2243) 12–17 years (n= 417) ‡18 years (n= 7315) All (n= 9975)
n% Mean SD Min Max n% Mean SD Min Max n% Mean SD Min Max n% Mean SD Min Max
Outpatient services
No. of contacts 2242 100.0 14.1 9.1 1.0 116.0 417 100.0 17.1 13.4 1.0 98.0 7306 99.9 30.8 23.9 1.0 392.0 9965 99.9 26.4 22.3 1.0 392.0
Phototherapy* 0 0.0 \5 – 226 3.1 230 2.3
Hospitalizations
No. of
admissions
319 14.2 1.4 1.0 1.0 14.0 73 17.5 1.7 1.5 1.0 9.0 2138 29.2 1.8 1.6 1.0 22.0 2530 25.4 1.7 1.5 1.0 22.0
No. of days 319 14.2 6.5 16.5 1.0 212.0 73 17.5 14.1 25.4 1.0 137.0 2138 29.2 13.8 21.7 1.0 303.0 2530 25.4 13.0 21.7 1.0 303.0
No. of
admissions
due to AD
12 0.5 1.4 0.9 1.0 4.0 5 1.2 1.8 0.8 1.0 3.0 77 1.1 1.2 0.5 1.0 4.0 94 0.9 1.2 0.6 1.0 4.0
No. of days due
to AD
12 0.5 9.3 7.6 1.0 27.0 5 1.2 16.4 14.4 3.0 40.0 77 1.1 14.2 16.2 3.0 103.0 94 0.9 13.7 15.3 1.0 103.0
Sick leave (adults, n = 6127)
No. of sick leave 2648 43.2 2.8 2.2 1.0 48.0
No. of days 2648 43.2 33.5 49.1 1.0 365.0
No. of sick leave
due to AD
200 3.3 1.2 0.5 1.0 5.0
No. of days due
to AD
200 3.3 24.0 48.7 1.0 359.0
Numbers which are too low or might allow indirect calculability of too low case numbers cannot be displayed due to data protection reasons
AD atopic dermatitis, SD standard deviation
*
Includes only outpatient phototherapy
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1937
Table 6 Healthcare resource utilization and associated costs in the 1-year observation period, stratified by age
2–11 years (n= 2243) 12–17 years (n= 417) ‡18 years (n= 7315) All (n= 9975)
n% Mean
cost [€]
Sum [€]n% Mean
cost [€]
Sum
[€]
n% Mean
cost [€]
Sum [€]n% Mean
cost [€]
Sum [€]
Outpatient services
Any contact 2242 100.0 507 1,136,386 417 100.0 610 254,199 7306 99.9 1096 8,005,964 9965 99.9 943 9,396,549
Phototherapy* 0 0.0 – – \5 – – – 226 3.1 102 23,090 230 2.3 101 23,300
Hospitalizations
Any admission 319 14.2 2291 730,958 73 17.5 5.082 370,993 2138 29.2 6391 13,664,133 2530 25.4 5836 14,766,085
Admission due to AD 12 0.5 3681 44,176 5 1.2 4.796 23,979 77 1.1 3333 256,611 94 0.9 3455 324,767
Medication
Any drug therapy 2243 100.0 372 834,169 417 100.0 857 357,428 7315 100.0 1524 11,147,820 9975 100.0 1237 12,339,417
AD-related systemic
drugs
2243 100.0 32 72,662 416 99.8 36 14,840 7302 99.8 68 497,104 9961 99.9 59 584,606
Other AD-related drugs
(excl. systemic drugs)
1454 64.8 38 55,917 221 53.0 65 14,282 4026 55.0 71 286,048 5701 57.2 62 356,247
Concomitant use of
TCI and TCS
4153 41.6 46 191,298
Sickness benefits
Any sickness benefit 0 0.0 – – \5 – – – 341 5.6 5026 1,713,841
Due to AD 0 0.0 – – 0 0.0 – – 22 0.4 6235 137,167
Numbers which are too low or might allow indirect calculability of too low case numbers cannot be displayed due to data protection reasons
AD atopic dermatitis, SD standard deviation, TCI topical calcineurin inhibitor, TCS topical corticosteroids
*
Includes only outpatient phototherapy
1938 Dermatol Ther (Heidelb) (2022) 12:1925–1945
adult patients with AD and SDTI, 5.6% received
sickness benefits (all-cause) and 0.4% received
sickness benefits due to AD. All-cause direct and
indirect costs were €8016 and €5026 per (adult)
patient per year among patients with AD and
SDTI, respectively. Direct and indirect costs due
to AD amounted to €3677 and €6235 per
(adult) patient per year, respectively, in the
population considered.
Discussion of findings
The focus of the present study was on patients
with AD and SDTI, i.e., patients with a first
documented health claim of systemic medica-
tion after a 1-year baseline period without a
respective claim. Characteristics of patients
with AD and SDTI showed a higher percentage
of females (57.8%) and a majority of patients
being 2–11 years old (22.5%). Consistent with
other research [29], more male than female
individuals were observed among young
patients (\18 years); whereas among adult
patients, a female predominance was observed.
Besides back pain and acute respiratory infec-
tions, in line with existing research literature
[4,30,31], bronchial asthma was revealed to be
one of the three most common comorbidities in
the considered patient population. This seems
expectable in light of epidemiologic and
pathophysiologic parallels reported in the lit-
erature [32].
Within the present analysis, the majority of
patients with AD and SDTI received SCS. Con-
sidering that evidence on the efficacy of SCS is
sparse and guidelines discourage their use
[12,33], these results are remarkable. Since
previous secondary [34–38] or registry data
analyses [4,39,40] differ in terms of the patient
population results can only be compared to a
limited extent.
Consistent with this study, a current study
from the US analyzing treatment patterns based
on claims data, found SCS to be the most fre-
quent systemic therapy initiated among
patients with AD [41]. However, this work
found a much higher proportion of patients
initiating systemic drug therapy with SCS
compared with the US study mentioned above
(99.2% vs. 73.4%) [41]. Differences within study
methodology (e.g., selection criteria, study per-
iod), as well as national differing prescribing
practices, may serve as an explanation. For
example, a recent study reported differences
between North America and Europe concerning
the choice of systemic therapy in pediatric
patients with AD among dermatologists [42].
Diversity concerning prescribing practices in
adult patients with AD was reported as well [43].
According to the guideline recommenda-
tions and a consensus paper of the International
Eczema Council, SCS should mostly be pre-
scribed due to an acute flare [11,12,33]. This
suggests that the SCS subgroup comprised
patients who were only treated systemically due
to an acute flare but may not have been eligible
for other systemic drug therapy options. How-
ever, since information on disease severity and
prescription reason were not available in the
analyzed database, the study results should be
interpreted with caution in this regard.
In the present study, the probability of being
under SCS-treatment after 27 days was still 50%.
The actual reasons for the discontinuation of
treatment were beyond the scope of this study
and the abilities of the analyzed database. Ger-
man guidelines recommend SCS treatment only
over ‘‘a few weeks’’ while European guidelines
even suggest a period of ‘‘up to 1 week’’ for the
treatment of acute flares of AD [11,12]. Con-
sidering the observed treatment duration
within this study, the use of SCS in most cases
was no longer in line with European guideline
recommendations.
The study findings showed that SCS were
also dispensed commonly in non-adult patients
with AD and SDTI despite their known side
effects (e.g., Cushing, osteoporosis, diabetes)
[44]. Due to an unfavorable risk–benefit profile,
guideline recommendations refer to a restricted
usage of SCS to adult patients; whereas usage in
non-adults should be handled cautiously
[11,12]. Although SCS are considered effective,
risk of relapse is high [11]. Nevertheless, SCS
were used in a large proportion of patients with
AD. The rapid achievement of clearing the AD
as well as a lack of other viable treatment
options serves as a possible explanation [33,45].
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1939
In the current study, only a small proportion
of patients with AD and SDTI received other
available systemic drug therapy options apart
from SCS, for example the licensed drugs
cyclosporine or dupilumab or off-label products
such as azathioprine or methotrexate. While
cyclosporine acts rapidly for acute flares of AD,
it may be contraindicated in some patients.
Cyclosporine is recommended for short- and
medium-term use in adult patients with
chronic, severe AD and may be considered in
children and adolescents with refractory, severe
disease course (off-label \16 years) [11,12].
According to the German guideline, the ratio of
expected benefits to risks must be examined
individually against the background of thera-
peutic alternatives when using cyclosporine in
the indication of AD [11]. It can be assumed
that cyclosporine is only used from a certain
disease stage onwards, weighing the benefits
against the risk for side effects. Thus, concern-
ing the observed rare use of cyclosporine, dis-
ease status and contraindications represent
potential factors.
Dupilumab was approved for adults in
September 2017 and adolescents in August 2019
[46]. Since it was only newly available for adults
on the German drug market during the time of
this study (the observation period covered only
1 year after index in year 2017), just a few
dupilumab cases (0.3%) could be observed. In
addition, dupilumab is recommended for
patients with moderate-severe AD whose disease
cannot be adequately treated with topical
medication alone [11].
In contrast to other study findings [30,41],
the share of patients who received any dispen-
sations for concomitant drug therapy by means
of TCS/TCI was relatively low (41.6%). A claims
data-based analysis of patients with AD using
advanced therapies reported 65.2% receiving
TCS; while 5.7% and 4.0% received tacrolimus
and pimecrolimus [41]. A Japanese study
reported an even higher rate with 86.7% of the
patients with moderate-severe AD receiving TCS
and/or TCI [30]. Extemporaneous preparation
are drugs individually prepared by a pharmacist
because an appropriate drug is not readily
available. As the latter were not identifiable in
the analyzed database, this may serve as an
explanation for the high percentage (58.4%) of
patients without any concomitant drug therapy
by means of TCS and/or TCI in the study find-
ings shown. TCS phobia, i.e., negative feelings
and beliefs related to TCS, has been reported in
the literature among patients with AD and their
caregivers [47], which may also have con-
tributed to the reduced number of patients
receiving TCS and/or TCI in this study. Fur-
thermore, patients were identified based on
their first observable dispensation of systemic
drug therapy in this analysis. Since claims data
do not include information on reasons for pre-
scriptions, it cannot be completely ruled out,
that included patients received systemic drug
therapy due to a comorbid condition other than
AD.
In line with other international studies, the
present findings show that HCRU of patients
with AD and SDTI within German healthcare
setting was primarily driven by outpatient visits
and pharmacy prescriptions [34,37].
There are some studies that analyzed AD-as-
sociated costs [21,37,41,48]. However, com-
parability of these studies with the present
study is limited due to differing target popula-
tions, different methodological approaches of
cost determination, and large differences in the
organization of the respective underlying
healthcare (e.g., Germany vs. USA). In line with
a German study from 2005, direct costs from
the SHI perspective were mainly driven by costs
of inpatient services, prescription drugs and
outpatient services [21]. Nevertheless, direct
costs were remarkably higher in the present
study. One explanation may be that costs for
inpatient services and medication have
increased since then due to general cost devel-
opments and the introduction of new treat-
ments. Another German study from 2021
showed that AD was associated with consider-
able out-of-pocket costs for healthcare (e.g.,
emollients), which can contribute substantially
to total AD-associated costs [24]. Considering
that the use of OTC medication could not be
assessed within the present study, reported costs
(for non-pharmacological topical AD treat-
ments) were likely underestimated.
1940 Dermatol Ther (Heidelb) (2022) 12:1925–1945
Strengths and limitations
The key strength of the present study was the
large, unselected, and nationwide sample. Thus,
estimations of patient characteristics, treatment
patterns, and HCRU are likely to be represen-
tative [25]. Since the study was based on rou-
tinely collected health claims data, non-
response or recall bias can be mitigated [49].
Nevertheless, the following limitations have
to be kept in mind when interpreting the results
of the study at hand. First, the InGef database
comprises data of different German SHI com-
panies; mainly, so-called ‘‘Betrieb-
skrankenkassen’’ and ‘‘Ersatzkassen’’. Thus,
estimates may be biased due to varying socio-
demographic information and information on
morbidity between the different types of SHI.
However, as previous analyses addressing the
external validity of the InGef database point
towards good overall accordance of the dataset
and the German population [12], biased esti-
mates are unlikely in this study.
Second, German health claims data do not
allow to obtain information on clinical param-
eters such as disease severity, reasons for treat-
ment discontinuation, or reasons for
prescriptions, as discussed above. Therefore, it
cannot be clearly stated from the analyzed
database whether the corresponding medica-
tion was actually used due to the AD diagnosis.
Moreover, no time frame (such as one quarter)
was specified in which both an AD diagnosis
and the dispensation of systemic drug therapy
had to be documented. Consequently, it cannot
be clearly stated if systemic drug therapies as
SCS were prescribed for AD or for any other
comorbid indication (e.g., allergic diseases
such as bronchial asthma) [16].
Third, some pharmaceuticals such as herbal
remedies and OTC drugs are usually not reim-
bursed by the SHI for patients aged C12 years;
whereas prescription drugs are covered in Ger-
many. Since many of the non-pharmacological
topical AD treatments are available as OTC, they
are mostly not represented in health claims data
and could therefore not be covered in the pre-
sent analysis.
Concerning the analyses of sickness benefits
and sick leave, it should be noted that not all
patients are entitled to sickness benefits or may
get sick leave. This includes freelancers and self-
employed, pupils, students, pensioners, and the
unemployed. Thus, analyses of sickness benefits
and sick leave will therefore always lead to an
underestimation of the actual burden. Addi-
tionally, it should be noted, that indirect costs
included only sickness benefits. In Germany,
sickness benefits are paid by the SHI funds from
the seventh week of illness to entitled insured
persons (see above). Since other cost elements,
such as productivity losses or reduced work
performance, were not considered, indirect
costs can be assumed to be underestimated.
HCRU was assessed during the 1-year period
following the first dispensation of a systemic
medication after 1 year without a correspond-
ing dispensation. Since no further restrictions to
moderate-severe cases were applied, it can be
assumed that less severe cases were potentially
overrepresented.
Finally, the current study focused on the
determination of current systemic treatment
patterns within the German health care setting.
Taking into account the new introduction of
dupilumab at the end of 2017, the study period
was chosen after its approval (2017/2018)
accordingly. Yet, the time period chosen may
not be fully representative of the current
healthcare situation with regard to systemic
drug therapy as it is likely that some patients
may not have had access to dupilumab imme-
diately after its approval.
CONCLUSIONS
This study provides real-world evidence of the
current treatment patterns of systemic drug use
and medical care situation of patients with AD
in Germany. Whereas other systemic drug
therapy options were rarely used, the results of
this study indicate a common use of SCS in
patients with AD and SDTI (including non-adult
patients) in Germany. The results suggest that
the duration of treatment with SCS and their
frequent use in non-adult patients exceed the
recommendations of current guidelines in the
majority of cases. They further suggest a
Dermatol Ther (Heidelb) (2022) 12:1925–1945 1941
substantial direct and indirect cost burden of
patients with AD and SDTI.
The results of this study should be inter-
preted cautiously in light of the described lim-
itations. Further research based on current real-
world data is needed to investigate the chang-
ing treatment situation with the availability of
dupilumab and other new systemic drug thera-
pies in Germany.
ACKNOWLEDGEMENTS
Funding. This study and the journal’s Rapid
Service Fee were sponsored by Pfizer in
Germany.
Medical Writing, Editorial and Other
Assistance. The authors would like to thank
Ariane Ho
¨er and Anja Mocek, employees of
IGES Institut GmbH, which was contracted and
reimbursed by Pfizer in Germany to design the
study, conduct the analyses, interpret the
results, and to write the manuscript, for pro-
viding pharmacological expertise and publica-
tion support, respectively. In addition, the
authors would like to thank Marie Sebald, a
former employee of Pfizer in Germany, for her
outcomes research expertise and publication
support. All three did not receive project-speci-
fic funding for their assistance.
Authorship. All named authors meet the
International Committee of Medical Journal
Editors (ICMJE) criteria for authorship for this
article, take responsibility for the integrity of
the work as a whole, and have given their
approval for this version to be published.
Author Contributions. Marie Schild, Agnes
Kisser, Christoph Ohlmeier, and Holger Gothe
were involved in the design of the study. Valeria
Weber, Wolfgang Galetzka, Dirk Enders, Chris-
toph Ohlmeier, and Holger Gothe were
involved in the analysis. Marie Schild, Valeria
Weber, Diamant Thac¸i, Agnes Kisser, Franziska
Zu
¨gel, Christoph Ohlmeier, and Holger Gothe
were involved in the data interpretation. Marie
Schild and Valeria Weber contributed equally to
this work and, thus, share the first authorship.
They wrote the manuscript with contributions
from Diamant Thac¸i, Agnes Kisser, Wolfgang
Galetzka, Dirk Enders, Franziska Zu
¨gel, Chris-
toph Ohlmeier, and Holger Gothe. All authors
read and approved the final manuscript.
Disclosures. All authors had complete
autonomy for the process of designing the
study, carrying out the analyses, interpreting
the results and writing the manuscript. This also
includes the full right to publish the results
without limitation. Agnes Kisser and Franziska
Zu
¨gel are paid employees of Pfizer in Germany.
Marie Schild was an employee of Pfizer in Ger-
many at the time of her contribution but is no
longer affiliated with Pfizer in Germany. Valeria
Weber and Holger Gothe are paid employees of
the vendor IGES Institut GmbH, which is a paid
consultant of Pfizer in Germany for designing
the study, carrying out the analyses, interpret-
ing the results and writing the manuscript.
Christoph Ohlmeier was a paid employee of the
vendor IGES Institut GmbH at the time of his
contribution but is no longer affiliated with
IGES Institut GmbH. Diamant Thac¸i worked as
investigator, consultant, and member of scien-
tific board or speaker for AbbVie, Amgen,
Almirall, Bristol-Myers Squibb, Biogen-Idec,
Boehringer Ingelheim, Dermira, DS Biopharma,
Eli Lilly, Galapagos, Galderma, Janssen-Cilag,
LEO Pharma, Novartis, Pfizer, Regeneron,
Roche-Possay, Samsung, Sandoz, Sanofi, Sun-
Pharma and UCB. Dirk Enders is an employee of
the vendor InGef, which was contracted and
reimbursed by the IGES Institut GmbH. Wolf-
gang Galetzka was an employee of the vendor
InGef at the time of his contribution but is no
longer affiliated with InGef.
Compliance with Ethics Guidelines. Since
all patient-level data in the database are anon-
ymized to comply with German data protec-
tions regulations and German federal law,
approval of an Ethics Committee was not
required. The research was conducted in accor-
dance with the Declaration of Helsinki.
Data Availability. The data used in this
study cannot be made available in the
1942 Dermatol Ther (Heidelb) (2022) 12:1925–1945
manuscript, the supplemental files, or in a
public repository due to German data protec-
tion laws (Bundesdatenschutzgesetz). To facili-
tate the replication of results, anonymized data
used for this study are stored on a secure drive at
the InGef GmbH. Access to the data used in this
study can only be provided to external parties
under the conditions of the cooperation con-
tract of this research project and can be assessed
upon request, after written approval (info@in-
gef.de), if required.
Open Access. This article is licensed under a
Creative Commons Attribution-NonCommer-
cial 4.0 International License, which permits
any non-commercial use, sharing, adaptation,
distribution and reproduction in any medium
or format, as long as you give appropriate credit
to the original author(s) and the source, provide
a link to the Creative Commons licence, and
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your intended use is not permitted by statutory
regulation or exceeds the permitted use, you
will need to obtain permission directly from the
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nc/4.0/.
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