10.5826/dpc.1401a79
Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease that negatively impacts the quality of life and work productivity of patients.
Objectives: We sought to evaluate the real-world burden of AD patients in Italy.
Methods: This sub-analysis of the MEASURE-AD multicountry study conducted between December 2019-2020 included patients diagnosed with moderate-to-severe AD eligible for receiving systemic therapy in the previous 6 months. During a single visit, physician and patient-reported questionnaires were used.
Results: A total of 118 adult patients were enrolled and 57.6% (N = 68) of patients had moderate-to-severe AD at the time of enrolment according to the Eczema Area and Severity Index.Sleep disorders interfered with daily function in the previous week in 58.5% (N = 69) of patients, pru-ritus was severe in 50% (N = 59) and 42.4% (N = 50) reported a flare lasting &gt;7 days in the previous 6 months.According to the Dermatology Quality of Life Index, 37.3% (N = 44) of patients reported a severe impact of AD and approximately 10% had clinical depression/anxiety. Current drug therapy was considered inadequate in controlling AD in 26.3% (N=31) of patients.Work activity impairment was 38.6±31.7% and monthly AD-related expenses were 148.6±134.6 Euros per patient.
Conclusions: This real-life study documents a high burden of disease in patients with moderate-severe AD in Italy.
text/xml
2160-9381
3865
en
Giovanna  Malara 
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
QoL
Burden of Disease in Real-Life Setting of Patients With Atopic Dermatitis: Italian Data From the MEASURE-AD Study
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-09-18
2024-01-31
2024-04-23
e2024079
Dermatol Pract Concept
Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease that negatively impacts the quality of life and work productivity of patients.
Objectives: We sought to evaluate the real-world burden of AD patients in Italy.
Methods: This sub-analysis of the MEASURE-AD multicountry study conducted between December 2019-2020 included patients diagnosed with moderate-to-severe AD eligible for receiving systemic therapy in the previous 6 months. During a single visit, physician and patient-reported questionnaires were used.
Results: A total of 118 adult patients were enrolled and 57.6% (N = 68) of patients had moderate-to-severe AD at the time of enrolment according to the Eczema Area and Severity Index.Sleep disorders interfered with daily function in the previous week in 58.5% (N = 69) of patients, pru-ritus was severe in 50% (N = 59) and 42.4% (N = 50) reported a flare lasting &gt;7 days in the previous 6 months.According to the Dermatology Quality of Life Index, 37.3% (N = 44) of patients reported a severe impact of AD and approximately 10% had clinical depression/anxiety. Current drug therapy was considered inadequate in controlling AD in 26.3% (N=31) of patients.Work activity impairment was 38.6±31.7% and monthly AD-related expenses were 148.6±134.6 Euros per patient.
Conclusions: This real-life study documents a high burden of disease in patients with moderate-severe AD in Italy.
Giovanna  Malara 
2024/01/31
10.5826/dpc.1401a79
e2024079
UOC of Dermatology, Grande Ospedale Metropolitano "Bianchi Melacrino Morelli", Reggio Calabria
2160-9381
QoL
en
e2024079
Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatology. 2021;157(9):1047-1055. doi:10.1001/jamadermatol.2021.3023
Burden of Disease in Real-Life Setting of Patients With Atopic Dermatitis: Italian Data From the MEASURE-AD Study
https://dpcj.org/index.php/dpc/article/download/3865/2412
         Burden of Disease in the Real-Life Setting
      of Patients with Atopic Dermatitis: Italian Data
               From the MEASURE-AD Study
      Giuseppe Argenziano1, Santo Raffaele Mercuri2, Paola Savoia3, Paolo Amerio4,
   Anna Belloni Fortina5, Maria Rita Bongiorno6, Maria Beatrice De Felici Del Giudice7,
Aurora Parodi8, Nicola Pimpinelli9, Luca Stingeni10, Michela Ortoncelli11, Giuseppe Stinco12,
 Giuliana Gualberti13, Anna Levi13, Valeria Scuderi13, Luca Bianchi14, Giovanna Malara15


 1 Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli,
   Naples, Italy
 2 Unit of Dermatology, IRCCS San Raffaele Hospital, Milan, Italy
 3 Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
 4 Dermatologic Clinic, Department of Medicine and Aging Science and Dermatologic Clinic, University “G. d’Annunzio”, Chieti-Pescara,
   Chieti, Italy
 5 Unit of Pediatric Dermatology, Department of Medicine DIMED, University of Padua, Padua, Italy
 6 Section of Dermatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties,
   University of Palermo, Palermo, Italy
 7 Dermatologic Unit, University Hospital of Parma, Department of Medicine and Surgery, Parma, Italy
 8 Division of Dermatology, Department of Health Sciences (DISSAL), University of Genoa, Genoa Italy and Ospedale Policlinico San
   Martino IRCCS, Genoa, Italy
 9 Dermatology Unit, Department Health Sciences, University of Florence, Florence, Italy
10 Dermatology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
11 Medical Sciences Department, Dermatologic Clinic, University of Turin, Turin, Italy
12 Institute of Dermatology, University of Udine, Udine, Italy
13 AbbVie SrL, Campoverde di Latina, Italy
14 Dermatology Unit, Tor Vergata University Hospital, Rome, Italy
15 UOC of Dermatology, Grande Ospedale Metropolitano “Bianchi Melacrino Morelli”, Reggio Calabria, Italy



Key words: real-life, moderate-to-severe atopic dermatitis, burden, QoL measures
Citation: Argenziano G, Mercuri SR, Savoia P, et al. Burden of Disease in Real-Life Setting of Patients with Atopic Dermatitis: Italian Data
From the MEASURE-AD Study. Dermatol Pract Concept. 2024;14(1):e2024079. DOI: https://doi.org/10.5826/dpc.1401a79
Accepted: September 24, 2023; Published: January 2024
Copyright: ©2024 Argenziano et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: AbbVie sponsored the study, contributed to the design; participated in data collection, analysis, and interpretation of the data, in
writing, reviewing and approval of the publication. No honoraria or payments were made for the publication.
Competing Interests: Paolo Amerio has received honoraria and speaker fees for: AbbVie, Janssen, Novartis, Sanofi, Amgen. Anna Belloni
Fortina has served as consultant and/or participated to advisory boards for Abbvie, Sanofi, Novartis, Cilag Janssen, Leopharma, Pfizer and
Artsana. Nicola Pimpinelli has the following conflicts of interest to disclose: BMS (unrestricted educational grant), Kyowa Kirin (advisory
board, unrestricted educational grant), Novartis (research grant), Pierre Fabre (speakers’ bureau), Recordati Rare Diseases (speakers’
bureau, unrestricted educational grant), Sanofi (speakers’ bureau), Takeda (advisory board, unrestricted educational grant). Michela
Ortoncelli has participated to advisory board and events for Abbvie, Sanofi, Lilly, Novartis, Leo Pharma. Aurora Parodi has participated
to clinical studies for Abbvie, Almirall, Galderma, Pfizer, Novartis, Leo pharma, Eli Lilly, Amgen, UCB. Luca Stingeni has been principal
investigator in clinical trials sponsored by and/or and has received personal fees from Abbvie, Celgene, Janssen, LeoPharma, Lilly, Novartis,
Regeneron, Sanofi, outside the submitted work. Luca Bianchi has served as speaker and consultant for Abbvie, Novartis, Janssen-Cilag,
Pfizer, UCB, Biogen, Leopharma, Sanofi, Eli Lilly, Sun Pharma, Sanitpharma outside the submitted work. Giuliana Gualberti and Anna Levi



Original Article | Dermatol Pract Concept. 2024;14(1):e2024079                                                                                 1
are AbbVie employees and may own AbbVie stocks/options. Valeria Scuderi is a former employee of Abbvie, and she is now affiliated with
Alfasigma SpA. All other authors have no conflict of interest to declare.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Professor Giuseppe Argenziano, MD, PhD, Department of Dermatology, University of Campania “Luigi Vanvitelli”,
Via Sergio Pansini 5, 80131 Napoli, Italy Phone: +39-0815666828 FAX: +39-0815468759
Acknowledgments: The authors wish to thank Sara di Fino and Chiara Palladino, of AbbVie, for critical reading of the manuscript and
Colin Gerard Egan (CE Medical Writing SRLS, Pisa Italy) for medical writing, funded by AbbVie.




    ABSTRACT           Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease that negatively impacts
                       the quality of life and work productivity of patients.
                       Objectives: We sought to evaluate the real-world burden of AD patients in Italy.
                       Methods: This sub-analysis of the MEASURE-AD multicountry study conducted between December
                       2019-2020 included patients diagnosed with moderate-to-severe AD eligible for or receiving systemic
                       therapy in the previous 6 months. During a single visit, physician and patient-reported questionnaires
                       were used.
                       Results: A total of 118 adult patients were enrolled and 57.6% (N = 68) of patients had
                       moderate-to-severe AD at the time of enrolment according to the Eczema Area and Severity Index.
                       Sleep disorders interfered with daily function in the previous week in 58.5% (N = 69) of patients, pru-
                       ritus was severe in 50% (N = 59) and 42.4% (N = 50) reported a flare lasting >7 days in the previous
                       6 months. According to the Dermatology Quality of Life Index, 37.3% (N = 44) of patients reported
                       a severe impact of AD and approximately 10% had clinical depression/anxiety. Current drug therapy
                       was considered inadequate in controlling AD in 26.3% (N=31) of patients. Work activity impairment
                       was 38.6±31.7% and monthly AD-related expenses were 148.6±134.6 Euros per patient.
                       Conclusions: This real-life study documents a high burden of disease in patients with moderate-severe
                       AD in Italy.




Introduction                                                             marketed, licensed, or are in the last stages of clinical devel-
                                                                         opment [3–5]. Development programs for these novel bio-
Atopic dermatitis (AD) is a chronic, inflammatory, skin dis-             logics are providing much better levels of evidence compared
order associated with significant disease burden. The burden             to older traditional drugs.
of AD mainly derives from signs and symptoms of AD which                      Substantial gaps in our understanding remain with regards
cause severe sleep loss in the first instance, then subsequently         to the overall burden of AD on patient health and wellbeing,
has a strong impact on quality of life (QoL), leading to the             particularly in patients with moderate-to-severe disease [6–9].
development of pathologies/conditions such as mental health                   Recent studies in moderate-to-severe AD report the pres-
disturbance, anxiety and depression as well as work/study                ence of a multidimensional disease burden [10–13] that in-
impairment [1,2].                                                        cludes other atopic comorbidities associated with pruritus
    Consensus based European guidelines recommend that                   such as sleep disturbance and functional impairment, and
adults with severe AD whose symptoms are not adequately                  secondary consequences including neuropsychiatric is-
controlled with topical agents should be considered for sys-             sues (anxiety, depression) and reduced health related QoL
temic treatments as well as immunosuppressants, photother-               (HRQoL) [1,14–16].
apy, or short-term oral corticosteroids for the management                    Nevertheless, few studies worldwide have specifically ex-
of acute flares [3]. Systemic therapy can be useful to reduce            amined the burden of moderate-to-severe AD across a wide
the total amount of topical corticosteroids in patients who              spectrum of QoL measures, particularly from the patients
need large amounts of potent topical corticosteroids for                 perspective [11,13,17–22].
large body areas over prolonged periods to control their AD.
    Indeed, the area of systemic therapy for the treatment
                                                                         Objectives
of AD has flourished in the past few years, as many new
substances (including inhibitors of IL-4 and IL-13 signaling             To address these gaps, this sub-analysis of the global
pathways as well as Janus kinase; JAK inhibitors) have been              cross-sectional MEASURE-AD study was performed on the



2                                                                             Original Article | Dermatol Pract Concept. 2024;14(1):e2024079
adult population in Italy to collect information on disease       Patient-Reported Disease Control
burden experienced by patients in terms of itching, skin pain,    Patient-reported disease control was assessed by asking pa-
sleep and mental disturbance as well as work productivity         tients to rate their degree of agreement with the validated
and out-of-pocket expenses.                                       statement, “I feel my current treatments are effective in con-
                                                                  trolling my atopic dermatitis.” Patients were also asked to
Methods                                                           report the number and average duration of AD flares in the
                                                                  previous 6 months.
Study Design
The MEASURE-AD study is a multicenter, cross-sectional,           Patient-Reported Sleep
observational study of patients with moderate-to-severe           Specific sleep-related questions were used to assess the im-
AD that aimed to assess the multidimensional burden of            pact of AD on sleep. These included: 1) average number of
disease, treatment pattern, and health care resources. This       hours slept per night in the past week, 2) average number of
sub-analysis of the MEASURE-AD study performed in Italy           minutes needed to fall asleep per night in the past week, 3)
evaluated AD patients enrolled between December 2019 and          number of nights in which sleep was disturbed over the past
December 2020 in a real-world setting.                            week, 4) sleep problems that interfered with daily function
                                                                  over the past week, 5) sleep problems that interfered with
Patients                                                          daily function over the past week.

Patients attending a routine visit, who fulfilled the following      The Atopic Dermatitis Impact Scale (ADerm-IS) ques-

selection criteria were included: a confirmed diagnosis of AD     tionnaire was also used to assess the impact of AD on sleep,

in patients aged ≥18 years with moderate-to-severe AD, pa-        daily activities and emotion [29].

tients who are (i) current candidates for systemic therapy for
                                                                  Patient-Reported Mental Health
AD, or (ii) currently receiving systemic therapy for AD, treat-
                                                                  The Hospital Anxiety and Depression Scale (HADS) was
ment history for the past 6 months; able to understand the
                                                                  used to assess Symptoms of anxiety and depression [31].
questionnaires, consent to use and disclose personal health
information and to participate in the study. Patients were ex-    Impact of AD on Work Productivity
cluded if they were currently participating in interventional
                                                                  The   Work     Productivity    and     Activity   Impairment
clinical trial(s). The study was conducted in accordance with
                                                                  Questionnaire–Atopic Dermatitis (WPAI-AD) was used to
the declaration of Helsinki and approval was obtained by
                                                                  measure impairment due to AD [32,33]. Scores were calcu-
all the Local Ethics Committees (first approval from Co-
                                                                  lated as percentages, with higher scores indicating greater
mitato Etico Università degli Studi della Campania “Luigi
                                                                  work productivity loss and activity impairment.
­Vanvitelli”, Prot N.: 766, on 05/12/2019).
                                                                  Out-of-Pocket Expenses
Outcome Measures                                                  Patients    documented     their     treatment    and   other
Disease Severity                                                  healthcare-related expenses each month (in Euro) due to
The extent and severity of AD were evaluated by derma-            their AD.
tologists through the Eczema Area and Severity Index
(EASI) [23,24] score according to Chopra [25] and Leshem          Statistical Analysis
[24]. Patients self-reported AD symptoms through the              Data are presented as mean and standard deviation for nor-
Patient-Reported Eczema Measure (POEM) [26].                      mally distributed variables or number and % for categori-
                                                                  cal variables. Statistical analysis was performed using SAS®
Itching/Pruritus
                                                                  Software (release 9.4, SAS Institute) on Microsoft Windows.
Numerical Rating Scales (0–10) for pruritus (Itch-NRS)
and the 5-D pruritus scale were used to assess the level of
­pruritus [27,28].                                                Results
Skin Pain                                                         Patient Characteristics
The ADerm-SS questionnaire was used to assess patient-            Baseline demographic and clinical characteristics of the study
reported skin pain [29].                                          population are summarized in Table 1. Sixty-three (53.4%)
                                                                  patients were male and mean age was 37.7±15.4 years. The
Impact of AD on HRQoL                                             mean age at disease onset was 13.3±17.9 years and a family
AD impact on health-related QoL was self-evaluated by patients    history of AD was seen in 44.1% (N =5 2) of patients. Most
through the Dermatology Quality of Life Index (DLQI) [30].        patients also had atopic comorbidities (78.8%; N = 93), the



Original Article | Dermatol Pract Concept. 2024;14(1):e2024079                                                                3
Table 1. Baseline clinical characteristics of atopic                38 (32.2%) patients, in combination with topical therapy
               dermatitis patients.                                 in 17 patients (14.4%) or in combination with topical and
                                                                    another systemic therapy in 1 (0.8%) patient.
     Clinical Characteristics         AD Patients (N = 118)
 General
                                                                    Outcome Measures
 Age (years)                                 37.7±15.4
                                                                    Disease Severity
 Male gender, N (%)                           63 (53.4)
              2                                                     Mean EASI score was 11.2±11.5 (Table 1) and 57.6% (N = 68)
 BMI (kg/m )                                  23.8±3.7
                                                                    patients were categorized as having moderate-to-severe AD
 Age of disease onset (years)                13.3±17.9
                                                                    according to Chopra (Figure 1A) while 53.4% (N = 63)
 Age at diagnosis (years)                    15.7±19.0
                                                                    ­patients were categorized as having moderate-to-severe AD
 Familial history of AD, n (%)                52 (44.1)
                                                                    according to Leshem (Figure 1B). Mean body surface area
 Education, N (%)                                                   (BSA) was 18.7±20.3% (Table 1) and 40.7% (N=48) of pa-
 Primary school                               14 (11.9)             tients were categorized as having moderate-to-severe AD ac-
 Secondary school                             68 (57.6)             cording to Chopra BSA AD severity (Figure 1C) [25].
 University or a higher education             36 (30.5)
 Comorbid diseases, N (%)                                           Sleep and the Impact of Itching/Pruritus
 Any atopic comorbidity                       93 (78.8)             The average number of hours slept per night in the past week
 Any non-atopic comorbidity                   40 (33.9)             was 6.5±1.7 and the average time needed to fall asleep per
 Not in therapy for AD, N (%)                  4 (3.4)              night was 31.1±31.7 minutes. In the past week, the average
                                                                    number of days with disturbed sleep was 2.7±2.5 days and
 Treatment, N (%)
                                                                    in 58.5% of patients (N = 69) sleep problems interfered with
 Topical treatment                            53 (44.9)
                                                                    daily function (Figure 2A).
 Current systemic treatment                   91 (77.1)
                                                                       The patient-reported 5D pruritus scale revealed that
    Dupilumab                                 67 (56.8)
                                                                    33.1% (N = 39) patients experienced delays falling asleep
    Cyclosporine                              19 (16.1)
                                                                    due to pruritus (Figure 2B).
    Systemic corticosteroids                   4 (3.4)
                                                                       Question 2 from the POEM questionnaire “Over the last
    Methotrexate                               4 (3.4)              week, on how many nights has your sleep been disturbed
 Phototherapy                                  5 (4.2)              because of your eczema?” revealed that as many as 41.5%
 Disease status                                                     (N = 49) patients had disturbed sleep due to eczema (Figure 2C).
 BSA (%)                                     18.7±20.3                 Mean scores for sleep, daily activities and emotional
 EASI score                                  11.2±11.5              state domains according to the ADerm-IS questionnaire were
                                                                    similar (ranging from 11.8 to 13.9) and the total ADerm-IS
AD = atopic dermatitis; BMI = body mass index; BSA = body surface
area; EASI = eczema area and severity index.                        score was 37.5±30.4 (Table 2). In terms of ADerm-IS single
Data are presented as number and % or mean ± SD.                    item scores, items relating to sleep disturbance were gener-
                                                                    ally higher compared to other items evaluated.
                                                                       Mean Itch-NRS was 5.4±3.4 and 65.3% (N = 77) of
most frequent being allergic rhinitis (48.3%; N = 57) or aller-     patients reported moderate or severe pruritus according to
gic asthma (33.9%; N = 40). Non-atopic comorbidities were           Vakharia scale (Figure 3A) [27].
also seen in approximately one-third of patients (33.9%; N             Question 1 from the POEM questionnaire “Over the last
= 40), the most frequent being hypertension, (12.5%; N =            week, on how many days has your skin been itchy because
15), anxiety (11.9%; N = 14), depression and diabetes (both         of your eczema?” showed that the majority of patients were
4.2%; N = 5).                                                       affected by itch skin because of their eczema in the past week
                                                                    and 65.3% (N = 77) were itchy ≥3 days in the past week
Current Treatment                                                   (Figure 3B).
The average time taken from diagnosis of AD to first treat-
ment was 139±177.4 months and to first systemic treatment           Skin Pain
was 231±169.4 months. Four patients (3.4%) were not re-             Mean score for ADerm-TSS-7 and ADerm-TSS-11 were
ceiving any treatment, while 53 patients (44.9%) were re-           32.4±21.9 and 47.8±33.5 respectively (Table 3). Lowest
ceiving topical treatment (Table 1). However, most patients         mean scores for quantitative variables evaluated were from
(77.1%; N = 91) were currently receiving systemic treat-            4 (worst skin cracking) to highest of 5.4 (worst dry skin)
ment. Just over half of patients were being currently pre-          and worst skin pain categories (7-10) accounted for 33.9%
scribed dupilumab (56.8%; N = 67), administered alone in



4                                                                       Original Article | Dermatol Pract Concept. 2024;14(1):e2024079
                                                                         Figure 2. The impact of itching/pruritus on sleep in patients with AD.
                                                                         (A) Proportion of patients categorized to what extent sleep problems
                                                                         interfered with daily function overt the past week. (B) Proportion
                                                                         of patients categorized to what extent pruritis interfered with their
                                                                         sleep according to Total 5-D. (C) Proportion of patients categorized
                                                                         to what extent their sleep was disturbed (in number of days) ac-
Figure 1. Disease severity in patients with AD. (A) Proportion of
                                                                         cording to question 2 of POEM questionnaire; “Over the last week,
patients categorized as having clear, mild, moderate or severe AD
                                                                         on how many nights has your sleep been disturbed because of your
according to EASI Chopra severity scale. (B) Proportion of patients
                                                                         eczema?”. POEM is a 7-item symptom inventory for eczema with
categorized as having clear, mild, moderate, severe and very severe
                                                                         a 1-week recall period. Scores range from 0–28, with higher scores
AD according to EASI Leshem severity scale. (C) Proportion of
                                                                         indicating worse severity of disease. Data are presented as %.
patients categorized as having clear, mild, moderate or severe AD
                                                                         AD = atopic dermatitis; POEM = Patient-Reported Eczema Measure.
according to BSA Chopra severity scale. The EASI score ranges
from 0 to 72, and according to Chopra was categorized as follows:
0 = clear, 0.1–5.9 = mild, 6–22.9 = moderate and 23-72 = severe.
                                                                         AD on DLQI were 41.5% (N = 49), 21.2% (N = 25) and
The EASI score according to Leshem was categorized as follows:
0 = clear, 0.1–1.0 = almost clear, 1.1-7 = mild, 7.1–21 = moderate and   37.3% (N = 44) respectively. In general, in >50% of patients,
21.1-50 = severe, 50.1-72 = very severe. Data are presented as %.        AD affected (a little or a lot/much) a physical, social, emo-
AD = atopic dermatitis; BSA = body surface area; EASI = Eczema           tional, and personal issues for a wide range of DLQI items.
Area and Severity Index.
                                                                         The proportion of patients responding to the item “itchy,
                                                                         sore, painful, stinging skin” were 10.8%, 39.2% and 45.8%
(N = 40) of patients and 51.7% (N = 61) rated their skin                 for “not at all”, “a little” or “a lot/very much” respectively.
pain as ≥4.
                                                                         Patient-Reported Disease Control and Presence
Impact of AD on HRQoL                                                    of Flares
Overall mean DLQI score was 8.7±7.3 and the proportion                   For 68 (57.6%) patients their current drug therapy was
of patients reporting a mild, moderate and severe impact of              considered effective, while 31 (26.3%) patients felt that



Original Article | Dermatol Pract Concept. 2024;14(1):e2024079                                                                               5
            Table 2. Results for ADerm-IS
                  Variable                         mean±SD
 Quantitative variables
 Sleep domain score                                11.9±10.2
 Daily activities domain score                     13.9±12.3
 Emotional state domain score                      11.8±10.3
 ADerm-IS total score                              37.5±30.4
 ADerm-IS single items
 Difficulty falling asleep due to AD                3.7±3.3
 Impact of AD on sleep                              3.8±3.5
 Bothered at night due to AD                        4.4±3.9
 AD limiting household activities                   3.7±3.5
 AD limiting physical activities                    3.3±3.3
 AD limiting social activities                      3.3±3.4
 Difficulty concentrating due to AD                 3.7±3.3
 Self-consciousness due to AD                       4.0±3.6
 Embarrassment due to AD                            3.8±3.5
 Sadness due to AD                                  4.1±3.8           Figure 3. The extent of itching/pruritus experienced by patients with
                                                                      AD. (A) Proportion of patients categorised as having mild, moderate
 The questionnaire was composed of 3 domains (sleep, daily activ-     or severe pruritus according to NRS Vakharia scale. (B) Proportion of
 ities and emotion) and an overall score as well as 10 single items
                                                                      patients categorized by the number of days that they were affected by
 (questions) based on the 3 domains. Three questions assessed the
 impact of AD over the previous 24 hours and 7 questions assessed     their pruritis in the past week according to question 1 of POEM ques-
 the impact over the past 7 days. Sleep domain score = questions      tionnaire; “Over the last week, on how many days has your skin been
 1-3, Daily activities domain score = questions 4-7 and Emo-          itchy because of your eczema?”. The level of pruritus was assessed in
 tional state domain score: questions 8-10. ADerm-IS total score:     the following NRS categories according to Vakharia: mild: 0-3, mod-
­questions 1-10.
                                                                      erate: 4-6 and severe: 7-10. The 5-D pruritus scale was a multidimen-
Each question displays a rating scale of answer options ranging       sional questionnaire to measure itch. The five dimensions are duration,
from 0 to 10 with a higher score indicating a larger (negative) im-   degree, direction, disability and distribution. 5-D scores ranged from
pact each score was calculated as sum of the contributing items. If
                                                                      5 (no pruritus) to 25 (most severe pruritus).Data are presented as %.
a contributing value was missing the score could not be calculated.
                                                                      AD = atopic dermatitis; NRS = Numerical Rating Scales; POEM =
AD = atopic dermatitis; SD = standard deviation.                      Patient-Reported Eczema Measure.
ADerm-IS = Atopic Dermatitis Impact Scale.


                                                                      Impact of AD on Work Productivity
their current treatment was inadequate in controlling their           Of the proportion of patients that were currently employed
AD. The mean number of flares reported in the previous 6              (N = 62; 52.5%), a mean presenteeism of 32.8±29.6%, mean
months was 3.5± 4.9 with over one-third (37.3%; N = 44) of            absenteeism of 7.1±18.1% and a mean overall work produc-
patients having ≥3 flares in the previous 6 months. Mean du-          tivity impairment of 36.1±30.9% were reported. The mean
ration of flares in the previous 6 months was 18±29.8 days            number of hours missed from work in the past 7 days was
and 42.4% (N = 50) of patients reported a flare duration              1.7±5.6. Overall work activity impairment on daily life was
greater than 7 days.                                                  38.6±31.7%.

Patient-Reported Mental Health                                        Out-of-Pocket Expenses
Mean anxiety score (HADS-A) was 6.3±4.1 with 35.6%                    Monthly healthcare-related expenses and monthly costs for
(N = 42) of patients having a HADS-A score of ≥8. Mean                everyday necessities due to AD were 90.1±93.9 Euro and
depression score (HADS-D) was 5.1±4 and 31.4% (N = 37)                56.7±63.1 Euro respectively with total monthly expenses of
of patients had a HADS-D score of ≥8. The proportion of pa-           148.6±134.7 Euro equating to 0.72±0.9% of annual fam-
tients categorized as having normal, borderline or abnormal           ily income.
anxiety or depression according to HADS are summarized
in Figure 4. Approximately two-thirds of patients reported
                                                                      Discussion
no pathological signs of anxiety or depression while approx-
imately 10% of patients reported having clinically relevant           In AD, it is recognized that increased disease severity is
anxiety or depression.                                                frequently correlated with a worsening in QoL of the



6                                                                          Original Article | Dermatol Pract Concept. 2024;14(1):e2024079
            Table 3. Results for ADerm-SS.                           or severe in 21.2% or 37.3%, respectively. Similarly, about
                                                                     one-third of patients were judged as having clear or mild
                 Variable                          mean±SD
                                                                     disease (by EASI) corresponding to a similar proportion of
 ADerm-TSS-7 score                                 32.4±21.9
                                                                     patients reporting no impact of their AD on sleep, pruritus
 ADerm-TSS-11 score                                47.8±33.5
                                                                     or QoL measures.
 ADerm-SS single items
                                                                         Previous real-life studies in Italy have recently evalu-
 Worst itch during sleep hours                      4.7±3.7
                                                                     ated the association of factors affecting QoL in AD pa-
 Worst itch during awake hours                      5.0±3.4
                                                                     tients [17,20,21,35,36]. Ferrucci and colleagues evaluated
 Worst skin pain                                    4.1±3.5          factors associated with poor QoL in 300 AD patients with
 Worst skin cracking                                4.6±3.3          severe ­
                                                                            disease (mean EASI was 29.45±7.1 and DLQI was
 Worst pain caused by skin cracking                 4.0±3.4          16.8±6.8) [35]. Poor quality of sleep was found to be a pre-
 Worst dry skin                                     5.4±3.4          dictor of anxiety symptoms, which is not surprising as anxiety
 Worst skin flaking                                 4.4±3.6          disorders are frequently associated with insomnia [37]. Ap-
 Worst rash                                         4.9±3.4          proximately half of patients had clinical anxiety or depressive
 Worst skin thickening                              4.2±3.4          symptoms (considering a HADS of ≥8) compared to approxi-
 Worst skin bleeding                                3.0±3.3          mately 30% in our study, likely reflecting the difference in the
 Worst skin oozing                                  3.0±3.3          severity of AD in patients in their cohort. Similarly, in their
                                                                     study, poor sleep, itch and depression were correlated with
AD-Derm-TSS-7= 7-item total symptom based on questions 1-7.
                                                                     each other, which again is to be expected and in turn to nega-
ADerm-TSS-11 score = 11-item total symptom based on questions
1-11. The ADerm-SS comprises 11 questions assessing experience       tively impact upon daily activities and consequently QoL [38].
of symptoms over the previous 24 hours. Each question displays a         These results corroborate with observations by Miniotti
rating scale ranging from 0 (no symptom) to 10 (worst experience
of symptom).                                                         et al where POEM, NRS for pruritus and sleep disturbance
                                                                     were significantly associated with DLQI and also in a small
AD = atopic dermatitis; SD = standard deviation.
ADerm-IS = Atopic Dermatitis Impact Scale.                           study by Milanesi et al where itch severity positively cor-
                                                                     related with sleep quality [17,21].
                                                                         In a post-hoc analysis of two randomized placebo-
                                                                     controlled phase-3 trials, Offidani et al., evaluated the
                                                                     ­improvement in signs and symptoms and QoL in patients
                                                                     with an EASI score of ≥20 to <24 or ≥24 treated with dupi-
                                                                     lumab for 16 weeks [36]. A weak correlation at baseline was
                                                                     observed between physician-assessed outcomes (reflected
                                                                     ­
                                                                     by EASI), patient-reported symptoms and QoL (reflected
                                                                     by pruritus NRS and DLQI) suggesting that patients with
                                                                     baseline EASI score of 20-24 can have substantial burden of
                                                                     disease and poor QoL. Indeed, patients with a substantially
                                                                     lower EASI (such as 11.2±11.5 in our study) can still be sig-
                                                                     nificantly burdened by their AD.
Figure 4. The impact of AD on anxiety and/or depression according
                                                                         The impact of AD on work productivity observed in our
to HADS questionnaire. HADS scores ranged from 0 to 21 for both
the subscales (anxiety and depression), with 0-7 = normal, 8-10 =    study confirm evidence from previous studies of AD [39–41].
borderline abnormal (anxiety or depression related symptoms), and    Indeed, we observed a significant impact of AD on both pre-
≥11 indicating abnormal (ie clinically relevant depression or anx-   senteeism and absenteeism with almost 2 hours missed from
iety). Data are presented as %. AD = atopic dermatitis; HADS =       work in the past week.
Hospital Anxiety (HADS-A) and Depression (HADS-D) Scale.
                                                                         In addition to the well-recognized work productivity and
                                                                     healthcare associated costs [42], the total monthly cost due
                                                                     to AD was estimated to be 148.6±134.7 Euro, similar to di-
patient [13,34]. Indeed, we observed that the proportion of          rect AD-related costs reported elsewhere [43].
patients with moderate (~30%) or severe (~20%) disease by                Information with regards to the current treatment pa-
the EASI or BSA closely reflect the proportion of patient with       tients’ satisfaction and their experience of this disease in
worse reported outcomes such as the proportion of patients           terms of its multi-faceted impact on an array of socio-physical
affected by sleep problems (58.8%), severe pruritus (50.0%)          issues are still limited.
and reporting a flare in the past week (42.4%). According                In our cross-sectional study we did observe that 37.3%
to the DLQI, the impact of AD was reported to be moderate            of patients had ≥3 flares in the past 6 months and over half of



Original Article | Dermatol Pract Concept. 2024;14(1):e2024079                                                                     7
patients were affected by disturbed sleep experienced ­severe      attending a routine visit were enrolled consecutively over
itching and markedly worse QoL. Over half of patients              a 6-month period, thereby reducing the potential for selec-
were assessed (by a dermatologist) as having moderate-             tion bias.
severe disease corresponding to a similar proportion of                Patients were required to describe their sleep and QoL
patients receiving systemic treatment. However, in our co-         over the previous week, thereby introducing the potential for
hort, we also observed long delays in diagnosis (~2 years),        recall bias. In general, a major limitation of population-based
diagnosis to first treatment (~10 years) and to first systemic     studies of the burden of AD is that they solely rely on patient
treatment (~19 years), pointing towards an important un-           responses.
met need in the awareness of this skin disorder and the ap-            Strengths of our study lie in the multicenter design of
propriate therapeutic management of these difficult-to-treat       current real-life management and treatment of adult patients
patients.                                                          with moderate-to-severe AD. Our findings grant a unique
    A recent nationwide campaign by The Italian Society            and in-depth perspective of the disease burden experienced
of Dermatology and Venereology, provided direct access to          by these patients.
27 dermatologic centers dedicated to the management of
AD and it was revealed that as many as 35% of patients
                                                                   Conclusions
received an incorrect diagnosis, almost 32% of patients were
untreated (either with topical or systemic agents) whereas         This real-life study highlights the impact of moderate-to-severe
44.3% used routine topical compounds, similar to the pro-          AD experienced by patients, a burden that is extensive and
portion in our study [22]. However, although mean EASI             varied. Besides physical symptoms such as pain and itching,
was similar in this cohort compared to our study (11.2), only      patients also experience a negative impact of AD on their
21.5% of patients had moderate-to-severe AD compared to            QoL as reflected by disturbed sleep, reduced workability,
~55% in our study, where we specifically selected these pa-        out-of-pocket costs, increased anxiety/depression, and re-
tients. It is widely accepted that there is an unmet need in       duced ability to carry out normal daily activities. Delays in
the management of AD and recent expert consensus has en-           diagnosis to first treatment and to first systemic therapy and
deavored to provide guidance in this regard [6] in addition        a high proportion of patients still receiving topical treatment
to recently published guidelines [3].                              (44.9%) may explain in part why approximately one-quarter
    As well as studies undertaken in Italy, data are also avail-   of patients were not satisfied with their current treatment. An
able from other large real-life studies evaluating the burden      awareness of the wide ranging and extensive burden from
and treatment patterns in AD patients from different coun-         this chronic inflammatory illness are paramount in order to
tries [11,13,44]. Collectively, these studies and ours, reveal     make important steps towards improving patient QoL.
that patients with moderate-to-severe AD report significant
disease burden, highlighting unmet treatment needs, with
particularly attention focused on the lack of/underuse of sys-
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