Healthcare Resource Utilization and Direct Cost of Patients with Atopic Dermatitis in Dubai, United Arab Emirates: A Retrospective Cohort Study

Atopic dermatitis (AD) is a relapsing–remitting, chronic inflammatory skin disease characterized by recurrent eczematous lesions and pruritus [1‐3]. AD typically appears during childhood, with approximately 85–90% cases being diagnosed before the age of 5 years, and the patients may attain remission before adulthood [4]. However, in some cases, AD may persist or relapse or may even have an onset in adulthood and may be difficult to treat [4].

The prevalence of AD is about 15–20% among children and 1–3% among adults [5], and varies widely across the globe owing to regional, country-specific, age-group-specific, and data-capturing methodological differences [6]. Evidence from several studies suggests that AD prevalence has reached a plateau in developed countries, whereas it continues to rise in low-income countries [5, 7‐10].

Management of AD begins with topical corticosteroids (TCS) followed by topical calcineurin inhibitor (TCI) such as pimecrolimus and tacrolimus, followed by later lines of therapy such as topical therapy of phosphodiesterase 4 inhibitor (crisaborole 2% ointment), systemic immunosuppressants, antimicrobials, phototherapy, and allergen-specific immunotherapy [3, 11, 12]. Recent approved additions to treatment management of AD includes biologics (such as dupilumab, tralokinumab) and JAK inhibitor (such as ruxolitinib, upadacitinib, abrocitinib) [13‐17]. The first biologic for AD treatment, dupilumab, was approved in 2017 [18]. Dupilumab, an interleukin-4 (IL-4) receptor alpha antagonist, has proven to be a safe drug for AD in all age groups, including adolescents from the age of 12 and elderly patients, as well as during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic [18‐23]. Alongside the initial lines of therapy, the basic therapy in the Middle East region includes use of emollients, trigger avoidance, and patient education [3].

Patients with AD are at increased risk of infections (such as Staphylococcus infection). Also, AD predisposes patients to abnormal immune response that may lead to cause atopic march, resulting in asthma and rhinitis [24‐29]. The intermittent infection among patients with AD substantially impacts individuals’ overall health status and quality of life [30, 31], along with increased utilization of healthcare resources [32]. The cost estimation (including both direct and indirect cost) for AD treatment in the USA was about 5 billion USD annually [33]. Another US study estimated 8.3 billion USD as the annual hospitalization cost incurred from 2002 to 2012 by patients with AD or eczema as primary diagnosis [34]. Although several global studies have indicated an increasing prevalence [5, 35, 36] and associated healthcare burden [31, 37, 38], there is a paucity of evidence on the burden of AD in the Middle East region, particularly in the United Arab Emirates (UAE).

The objective of the current study was focused at understanding the real-world economic burden of insured expatriates AD in terms of direct medical cost [healthcare resource utilization (HCRU) and related costs], specialties that diagnose AD and treatment landscape. This study also analyzed consultation-based prevalence and incidence rates, as well as patient characteristics in terms of demographic characteristics and disease severity. Also, this study aimed to address the existing knowledge gap and inform the local and regional healthcare guidelines for AD management.

This is the first-of-its-kind secondary database analysis of insurance e-claims database wherein patients (insured expatriates) with AD in Dubai (UAE) were evaluated for direct medical costs in terms of HCRU costs, specialties involved in diagnoses of AD, and treatment patterns. Across the cohorts in the study, the mean age (latest available age at the time of data abstraction) of patients was about 29 years. In this study, age- and gender-wise distribution of AD was being evaluated; however, conclusions could not be drawn owing to availability of only 50% of the patients for these variables. Nevertheless, from the available data of 50% of patients, it was observed that the majority (approximately 65%) of the patients belonged to the age group of 18+ years. This finding is consistent with a few global studies that have indicated increased prevalence of AD among adults with an onset after 18 years of age [40‐42]. Furthermore, this finding is in line with a 2017 global survey involving 18 countries that indicated an increased prevalence of AD with age, lowest among infants, whereas highest during adulthood, and slightly lower prevalence in adolescents [43, 44]. While a few of the studies had indicated AD to be more prevalent in females than males [35, 45, 46], the data analysis from this study indicated otherwise (male ~ 60% and female ~ 40%).

AD is known to coexist with conditions such as bronchial asthma, allergic rhinitis, allergic contact dermatitis, and food allergies [47, 48]; and is also associated with increased risk of bacterial infection [49]. The wide variability of clinical presentation of bacterial infection in AD often overlaps with the inherent clinical characteristics of AD, making its diagnosis even more challenging [49]. One of the previous studies concluded that there are many epidemiologic parallels between asthma and AD, and it is observed that asthma occurs in children with AD later during their childhood [50]. Longitudinal studies have also demonstrated an association between severity of AD and occurrence of asthma and allergic rhinitis in children [51, 52]. Analysis of pre-index period data of the treated patients with AD who were hospitalized showed that 4.5% (n = 38) and 5.5% (n = 16) of patients had asthma among mild-to-moderate treated AD patients and moderate-to-severe treated AD patients, respectively.

In this study, among mild-to-moderate treated AD cohorts, the most commonly prescribed drug class was TCS, followed by antihistamines and TCI, and this trend is in line with a similar study conducted in Germany [46]. The long-term management of mild-to-moderate AD is based on recent guidelines and efficacy study; thus, the management includes proactive therapy with TCS and TCIs (tacrolimus) [1, 53]. This study indicated a switch pattern that is in line with previous studies, which showed that switch between TCIs and TCSs is common, depending upon the disease severity and symptom control conferred by the treatment [54]. The switch-overs were comparatively higher from first-line TCS to second-line TCI among patients of the mild-to-moderate group along with addition of TCI as first add-on to an ongoing TCS. From the very limited available data on switch pattern among moderate-to-severe treated AD patients, it was noted that three patients switched from the first-line corticosteroids to biologics, and one patient had an addition of corticosteroid to an ongoing biologics treatment.

With regard to antihistamine use, the clinical guidelines by American Academy of Dermatology Association recommends limited use of antihistamines, especially topical antihistamines due to absorption and risk of contact dermatitis [1]. On the contrary, a recent study on German population showed that 23.5% of patients used antihistamines [46]. Furthermore, this study also indicated substantially higher usage of antihistamines in Dubai: 52% of mild-to-moderate treated AD patients had 7689 (47%) antihistamines claims, and 65% of moderate-to-severe treated AD patients had 4227 (45%) antihistamines claims.

An earlier claims database study conducted in the USA indicated increased HCRU among patients with moderate-to-severe AD compared with those with mild-to-moderate disease [55]. An observational cohort study from the Netherlands reported a significant increase in direct cost due to systemic immunosuppressive treatment use among patients with moderate-to-severe AD [56]. Although this study revealed of highest HCRU in the moderate-to-severe treated AD cohort, the claims made for immunosuppressive agents were very low in the moderate-to-severe cohort. This study indicated that main drivers of direct medical cost were hospitalizations, outpatient visits, supplies, and consumables, followed by procedures and medications.

A 2019 review article on the socioeconomics of AD concluded that AD incurs substantial direct cost among patients with AD, including for their family and payers as well [57, 58]. A 2013 study on burden of skin disease indicated that, among various skin diseases, total burden of dermatitis (atopic, contact, and seborrheic dermatitis) in terms of disability-adjusted life years was highest at 0.38%, followed by acne vulgaris (0.29%), psoriasis (0.19%), urticaria (0.19%), etc. [58]. An earlier 2004 US study on economic burden of skin disease showed a higher annual cost among patients with AD (4.228 billion USD) than patients with psoriasis (3.658 billion USD) [59]. The increased direct AD costs has been shown by various studies: one such 2013 US study showed annual direct cost to be between 252 USD million and 314 USD million [60], and a 2015 Korean study estimated per patient annual cost of 2,646,372 Korean Won (KRW) (2088 USD; exchange rate as of 18 May 2022) [61]. A recent retrospective US database study reported a significant increase in direct cost among adult patients with AD: 938 USD in 2016 and 1466 USD in 2017 [34, 60].

This study reported per-patient gross cost of 531.5 USD, 378.48 USD, and 144.04 USD among moderate-to-severe treated AD cohort, mild-to-moderate treated AD, and untreated AD cohort, respectively. Thus, the higher overall annual HCRU-associated costs were reported by the moderate-to-severe treated AD cohort, followed by the mild-to-moderate treated AD cohort. When all-cause cost was considered, the moderate-to-severe treated AD cohort had higher cost than the mild-to-moderate treated AD cohort even for patients hospitalized with asthma (3176.5 USD versus 2386.1 USD, respectively) or allergic rhinitis (2781.7 USD versus 2287.8 USD, respectively). Thus, the study indicated that asthma and allergic rhinitis are important drivers of overall HCRU and cost burden when all causes are considered. However, this result could not be interpreted for AD-specific HCRU burden because of limited data available for analysis. The available results indicate higher HCRU associated with moderate-to-severe disease than mild-to-moderate disease, and thus, an early intervention could reduce the overall HCRU burden.

There are certain inherent limitations associated with the study based on e-claims database that can impact the study interpretation. The study sample covered only private insured expatriate population of Dubai (UAE), mostly representative of the population who were from a different country of origin but settled in Dubai either temporarily or permanently for an extended period. Thus, this database does not consider the local population covered by public funding, who were not a part of Dubai Private Insurance. Also, a filled prescription e-claim is not indicative of the medication being consumed or taken as prescribed and thus can be used only as a surrogate measures for AD severity rather than an objective clinical measure. As a general guidance for management of AD, most of the patients irrespective of the AD severity may be using nonmedicated topical therapy (such as emollients) that are not recorded in this database. The patients considered under untreated or on drugs not included in the treated AD cohorts may be on mild disease using emollients or other medication for which no prescription was filled or allocation in severity, thus leading to difficulty in establishment of severity of AD as mild and moderate. The variability in treatment pattern across providers cannot be ruled out and may introduce information bias. Another limitation included the availability of biologics for AD treatment in Dubai (UAE). The e-claims data may be subject to disease-coding inaccuracies, attributable to inaccurately coded or included as rule-out criteria rather than “actual disease,” leading to misclassification bias. Furthermore, information pertaining to certain clinical and disease-specific parameters is not readily available in the e-claims database. Additionally, the DRWD database only provides information that a specific medication or a service was availed but does not allow one-to-one mapping between diagnosis and medication/procedure/consumables. Thus, the overlap of patients between the mild-to-moderate and the moderate-to-severe treated AD cohort cannot be ruled out as severity categorization was based on treatment prescribed. Furthermore, for patients aged < 1 year, a 12-month pre-index period was not applicable, and therefore, they were not considered in the study for HCRU, treatment pattern patient characteristics analysis. Moreover, it was noted during the data analysis that the age and gender data were available for only about 50% of the patients, hence limiting the interpretation of the results in relation to patient demographics and disease severity evaluation. Finally, the study evaluated only the economic burden in terms of direct healthcare costs without considering the indirect costs (work productivity and quality of life) in the evaluation of the economic burden of AD. Some of these challenges can be overcome in future by updating database for relevant variables, as appropriate. Despite of the limitations, the DRWD is a rich source of information that has provided insights into direct cost utilization and treatment patterns based on specialties involved.

This study indicated AD to be a common skin disease with a prevalence rate of 4–5% in Dubai (UAE), with the majority of patients (about 90%) being treated by specialists. However, there is a significant underuse of newer innovative therapies (including biologics). Also, disease severity (moderate-to-severe AD) was associated with high direct medical cost, which could be controlled by early intervention. Furthermore, AD treatment choice could focus on major direct HCRU cost contributors such as hospitalizations, comorbid conditions, and infections.