FormalPara Key Summary Points

Why carry out this study?

Despite high prevalence of atopic dermatitis (AD) among patients with skin of color in the United States and Canada, the literature on sociodemographic, clinical, and treatment characteristics is limited.

It is important to characterize differences in sociodemographic, clinical, and treatment characteristics among race/ethnicity groups in real-world AD patients who are candidates for or are currently prescribed systemic therapy.

What was learned from the study?

Racial and ethnic differences exist in sociodemographic, clinical and treatment characteristics, disease severity, and patient-reported outcomes among real-world AD patients with AD who are candidates for systemic therapy.

Racial and ethnic differences should be taken into consideration when treating patients with AD.

Recognizing these differences may be of critical importance for dermatologists for the design and delivery of targeted/personalized medicine approaches.

Introduction

Atopic dermatitis (AD), is a chronic, heterogeneous, inflammatory skin disease affecting up to 7% of the US adult population [1,2,3,4,5]. The prevalence of AD has increased over the past few decades [6] and varies within and between countries [7,8,9].

The pathophysiology of AD involves a complex interplay of genetics, immune dysregulation, skin-barrier dysfunction, and environmental factors [7, 8, 10,11,12,13,14,15,16]. AD is a polymorphic disorder, manifesting with erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and lichenification. Pruritus is universal and is the most burdensome symptom of AD for patients and their families [17].

The clinical presentation and severity of AD varies widely among races and ethnicities [18,19,20]. Active AD lesions may present with violaceous or brown tones in patients with skin of color [21]. Patients of East Asian ancestry may present with well-demarcated lesions with prominent scaling and lichenification [19], and sometimes psoriasiform lesions [21]. Black patients may present with papular and perifollicular lesions, lichen planus-like lesions, and may have more extensor involvement [21, 22]. In Black patients, lichenification and prurigo nodularis are observed more than in White patients, potentially because of greater pruritus or difficulty assessing erythema in patients with skin of color [22,23,24].

Assessment and management of AD should include consideration of potential unmet needs in racially diverse patients [25,26,27]. Few studies have examined differences of disease severity and presentation, and patient-reported outcomes (PROs) in diverse patient populations.

This study compared sociodemographic, clinical and treatment characteristics, disease severity, and PROs across racial/ethnic groups in patients with AD who were candidates for and/or were currently prescribed systemic therapy in the United States and Canada, using real-world data from the CorEvitas AD Registry.

Methods

Data Source and Patient Population

The CorEvitas AD Registry is a large, independent, prospective, observational, non-interventional registry for patients with AD diagnosed by a dermatologist or a qualified dermatology practitioner. The registry enrolls adult patients (≥ 18 years) who (a) initiated systemic therapy within 12 months prior to the enrollment visit, (b) were prescribed systemic therapy at the enrollment visit, or (c) were untreated with systemic therapy but had moderate-to-severe AD with Eczema Area Severity Index (EASI) score ≥ 12, and vIGA-AD® ≥ 3 at the enrollment visit. Patients participating in or planning to participate in a double-blind randomized trial for a systemic AD medication were ineligible for registry enrollment. For purposes of determining eligibility, systemic therapy included biologics (dupilumab, ixekizumab, omalizumab, risankizumab, secukinumab, ustekinumab), non-biologics (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, mycophenolic acid, tacrolimus), and small molecules (montelukast sodium, apremilast, baricitinib, tofacitinib, upadacitinib). A few biologics (risankizumab, secukinumab, ustekinumab) and a small molecule (tofacitinib) were included in the list of eligible medications for enrollment in the registry to capture any potential off-label use of systemic therapy for AD.

Longitudinal data were collected from both patients and their treating providers during routine clinical encounters using a standardized data collection method. The scope of data collection included but was not limited to patient demographics (including age, sex, race, and ethnicity), medical history (including all prior and current treatments for AD), disease phenotype and duration, smoking status, alcohol use, disease activity and severity, as well as other clinician- and patient-reported outcomes, comorbidities and adverse events, infections, hospitalizations, and other targeted safety outcomes.

This cross-sectional study used data collected from the CorEvitas AD Registry during enrollment visits that occurred from July 21, 2020 through July 28, 2021. For the study period, the registry included 53 private and academic clinical sites with 102 clinicians throughout the US and Canada with 1298 enrolled patients with AD.

All patients were required to provide written informed consent prior to participating. All participating investigators were required to obtain full board approval for conducting research involving human subjects. Sponsor approval and continuing review was obtained through a central Institutional Review Board (IRB; IntegReview, protocol number Corrona-AD-550). For academic investigative sites that did not receive a waiver to use the central IRB, approval was obtained from the respective governing IRBs and documentation of approval was submitted to the Sponsor prior to initiating any study procedures. All registry subjects were required to provide written informed consent prior to participating.

Measures

Patients were categorized into five groups based on self-reported race/ethnicity: White-non-Hispanic (White), Black-non-Hispanic (Black), Asian-non-Hispanic (Asian), Other/Multiracial-non-Hispanic (Other/Multiracial) and Hispanic-any race (Hispanic).

Patients’ sociodemographic, clinical, and treatment characteristics were assessed at the time of registry enrollment. Primary outcomes included disease severity (measured using vIGA-AD® [28], EASI [29], and SCORing for AD [SCORAD]) [30] and PROs (assessed using the Patient-Oriented Eczema Measure [POEM] [31], peak pruritus-numeric rating scale [NRS] [32], and AD Control Tool [ADCT]) [33]. Detailed descriptions of PRO measures are provided in the Supplementary Table 1.

Secondary outcomes included specific AD clinical features for which descriptive analyses demonstrated small-to-large effect sizes (ES) for differences by race/ethnicity (phi > 0.10), provided that the overall prevalence in the study cohort was > 5%.

Statistics

Sociodemographic, clinical, and treatment characteristics were summarized descriptively using frequencies with percentages for categorical variables and means with standard deviations for continuous variables. Differences in means or proportions of characteristics among race/ethnicity groupings were descriptively summarized using ES: categorical (phi: 0.10, 0.30, and 0.50 for small, moderate, and large differences, respectively) [34] and continuous (Cohen’s f: small, moderate, and large for values of 0.10, 0.25, and 0.40, respectively) measures [35]. Adjusted prevalence ratios (dichotomous outcomes) and mean differences (continuous/ordinal outcomes) were estimated with 95% confidence intervals (CI) using multivariable mixed effects Poisson and linear regression models, respectively. These adjusted estimates were reported using the White race/ethnicity group as the reference category. Separate models were fitted for each outcome and were adjusted for prespecified covariates (age, sex, geographic region, age of AD symptom onset, prior medications [systemic therapy, systemic corticosteroids, phototherapy, super-potent topical steroids], history of asthma, history of allergic rhinitis, history of eosinophilic esophagitis, history of food allergies), as well as any covariate with at least a moderate difference observed in any race/ethnicity group versus White patients. Statistical significance was defined as p < 0.05; no adjustments were made for multiple comparisons. All statistical analyses were conducted using Stata Release 16 (StataCorp LLC, College Station, TX, USA).

Results

Sociodemographic Characteristics

Overall, 1288 (99%) patients provided information on race and ethnicity, including 167 (13%) Black, 129 (10%) Asian, 97 (8%) Hispanic, 73 (6%) Other, and 822 (64%) White patients. Mean ± SD age in years at enrollment ranged from 38.6 ± 16.4 (Asians) to 52.9 ± 17.7 (Whites, ES = 0.31). Most patients across all racial/ethnic groups were female (range: 59–67%, ES = 0.06). Most of the patients across all racial/ethnic groups reported adult-onset AD. Adult-onset AD was reported more commonly in White patients (70%) than Black (57%), Asian (44%), Other/Multiracial (52%), and Hispanic patients (56%; ES = 0.21; Table 1).

Table 1 Patient demographics and clinical characteristics at enrollment by race/ethnicity groups among patients enrolled in the CorEvitas AD Registry
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A moderate difference was observed both in work status (ES = 0.30) and geographic region (ES = 0.45) across all racial/ethnic groups. Black patients (51%, 16%) were more likely to work full-time or be disabled than White (45%, 10%), Asian (45%, 2%), Other/Multiracial (42%, 10%), or Hispanic (47%, 5%) patients. White patients were most often from the Midwest (44%), whereas Black patients were most often from the South (51%) and Asian, Other/Multiracial, and Hispanic/Latino patients were most often from the West (43%, 33%, and 43%, respectively). Small ES differences were noted for health insurance type: private/commercial health insurance (range: 52% Other/Multiracial to 70% White; ES = 0.11), Medicare (range: 6% Hispanic to 25% White, ES = 0.19), and Medicaid (range: 10% White to 34% Black, ES = 0.24; Table 1).

Clinical Characteristics

AD lesion locations that varied at enrollment with a small ES (0.12–0.15) included palmar hands (20% Hispanic to 39% White), plantar feet (12% Asian to 25% White), face (42% Black to 62% Asian) and neck (40% White to 63% Asian). Other lesion locations did not meet criteria for ES differences (Table 2).

Table 2 Lesion locations and AD clinical features present at enrollment, by race/ethnicity group, among patients enrolled in the CorEvitas AD Registry
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Clinical features with overall prevalence > 5% and small differences (ES: 0.10–0.19) observed by race/ethnicity included perifollicular accentuation (6% White to 17% Black), prominent head-neck involvement (19% White to 35% Asian), flexural lichenification (range: 21% for White and 33% for Black), facial erythema (6% Black to 28% Asian), allergic shiners (6% White to 21% Other/Multiracial), and Dennie–Morgan fold (7% Black to 21% Other/Multiracial; Table 2).

Disease Severity and Patient-Reported Measures

No statistically significant differences were observed at enrollment by race/ethnicity in vIGA-AD, EASI, or SCORAD. Adjusted analysis of disease severity measures at enrollment identified more severe EASI lichenification in Black patients vs White patients (mean difference, head and neck, 0.21, 95% CI [0.06, 0.36], p = 0.01; trunk, 0.32 [0.17, 0.47], p < 0.001; upper extremities, 0.27 [0.09, 0.44], p = 0.008; lower extremities, 0.39 [0.21, 0.57], p < 0.001) (Fig. 1A, Supplementary Table 2). In adjusted analysis, more severe findings were also noted in Black vs White patients for SCORAD lichenification (mean difference 0.31 [0.15, 0.47], p < 0.001) and SCORAD dryness (0.27 [0.11, 0.43], p = 0.01; Fig. 1B). Adjusted mean difference EASI erythema scores for Black patients vs White patients were: head and neck, − 0.02 (− 0.20, 0.15); trunk, 0.01 (− 0.17, 0.18); upper extremities, − 0.05 (− 0.22, 0.12); and lower extremities, 0.07 (− 0.11, 0.26).

Fig. 1
figure 1

Adjusted differences in measures at enrollment compared with White patients. A EASI, B SCORAD, C average pruritus over the past 7 days, and D clinical features. Models adjusted for age, sex, geographic region, age of AD symptom onset, prior medications (systemic therapy, systemic corticosteroids, phototherapy, super-potent topical steroids, crisaborole, topical calcineurin inhibitors), history of asthma, history of allergic rhinitis, history of food allergies, work status and BMI. The models included random intercepts for site and provider. Estimates in reference to White patients. BMI, body mass index; EASI, eczema area severity index; SCORAD, scoring atopic dermatitis

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Statistically more severe EASI lichenification was observed in certain areas among Asian vs White patients (adjusted mean difference head and neck, 0.22 [0.04, 0.39], p = 0.01; trunk, 0.25 [0.07, 0.43], p < 0.001; lower extremities, 0.22 [0.01, 0.43], p < 0.001 and SCORAD lichenification (adjusted mean difference 0.34 [0.15, 0.52], p < 0.001) (Fig. 1A, B, Supplementary Table 2). Although not significant, adjusted mean difference EASI erythema score for Asian vs White patients were: head and neck, 0.14 (− 0.06, 0.35); trunk, 0.11 (− 0.10, 0.32); upper extremities, − 0.08 (− 0.28, 0.12); lower extremities, 0.04 (− 0.18, 0.25). The adjusted analysis also identified significantly higher mean pruritus over the past 7 days for Black (mean difference 0.60 [0.11, 1.09], and Hispanic patients (0.63 [0.01, 1.26], p = 0.03) vs White patients (Fig. 1C, Supplementary Table 2). No statistically significant adjusted mean differences were identified for POEM, worst pruritus in past 24 h, or ADCT.

When clinical features at enrollment were examined by multivariable analysis, the prevalence of facial erythema was statistically lower among Black patients vs White patients (prevalence ratio = 0.38 [0.22, 0.67]; p = 0.007), and prevalence of allergic shiners was higher among Black (2.65 [1.72, 4.07]), Asian (1.93 [1.34, 2.80]), and Other/Multiracial (1.88 [1.22, 2.89]) patients vs White patients (p < 0.001; Fig. 1D, Supplementary Table 2). Other observed clinical features did not reach statistical significance.

When EASI severity of signs was dichotomized into moderate/severe vs none/mild, Asian patients had a higher prevalence of moderate/severe edema/papulation in all areas (head and neck prevalence ratio, 1.42 [1.10, 1.84]; trunk, 1.54 [1.17, 2.01]; upper extremities, 1.21 [1.01, 1.46]; lower extremities, 1.35 [1.07, 1.72]) compared with White patients. Although not all differences were statistically significant, Asian patients had a higher prevalence of moderate/severe EASI lichenification in all areas, (head and neck 1.30 [0.91, 1.87]; trunk 1.55 [1.15, 2.11]; upper extremities 1.35 [1.06, 1.72]; lower extremities 1.21 [0.92, 1.58]). In addition, Asian patients had a higher prevalence of moderate/severe SCORAD swelling (1.39 [1.14, 1.69]) and lichenification (1.53 [1.24, 1.90]) versus White patients; Supplementary Table 3).

Compared with White patients, Black patients had a higher prevalence of moderate/severe EASI lichenification in all areas, although not all differences were statistically significant (head and neck, 1.47 [1.02, 2.13]; trunk, 1.50 [1.21, 1.86]; upper extremities, 1.24 [0.98, 1.55]; lower extremities, 1.50 [1.19, 1.90]). Black patients also had a higher prevalence of EASI edema in the lower extremities (1.27 [1.04, 1.55]), and a higher prevalence of moderate/severe SCORAD lichenification (1.32 [1.06, 1.64]; Supplementary Table 3).

In unadjusted analysis, no statistically significant differences were observed by race/ethnicity among disease severity and PRO measures (vIGA-AD, EASI, SCORAD, POEM, and ADCT; Supplementary Table 4).

Treatment Characteristics

Pre-enrollment history of systemic therapy ranged from 40% to 50% among all racial/ethnic groups (ES = 0.04); history of systemic corticosteroids and phototherapy were slightly higher among Asian (37%, 20%) and Other/Multiracial (42%, 15%) patients, in comparison to White (18%, 10%), Black (23%, 7%), and Hispanic (20%, 7%) patients (systemic corticosteroids ES = 0.19; phototherapy ES = 0.12; Fig. 2A). The proportion of patients currently taking systemic therapy ranged from 76% to 92% among all racial/ethnic groups (ES = 0.12). Current use of topical calcineurin inhibitors and crisaborole was slightly higher among Asian (36%, 16%) patients in comparison to other racial/ethnic groups (range 15–25%, 4–7%; ES = 0.15 for both; Fig. 2B).

Fig. 2
figure 2

A Treatment characteristics among patients enrolled in the CorEvitas AD Registry by race/ethnicity group. A History of prior treatmentc. B Current treatmentc. aSystemic therapy included biologics (dupilumab, ixekizumab, omalizumab, risankizumab, secukinumab, ustekinumab), non-biologics (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, mycophenolic acid, tacrolimus), and small molecules (apremilast, baricitinib, montelukast sodium, tofacitinib, upadacitinib); bSystemic corticosteroids included methylprednisolone (injection or oral), prednisone oral, and triamcinolone injection (intralesional or intramuscular); cNot mutually exclusive; dGroup denominator may be smaller than group total shown, but nonresponses were < 1%

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Discussion

Among real-world AD patients who are candidates for systemic therapy, we observed differences in age of AD symptom onset, work and health insurance status, geographic region, lesion location, treatment characteristics and clinical features across racial and ethnic groups. In adjusted analyses, differences were noted for EASI lichenification, SCORAD lichenification and dryness, average pruritus over the past 7 days, and the clinical features facial erythema and allergic shiners. Previous studies showed differences in prevalence, disease severity, and persistence of AD across different racial/ethnic groups in the US [22, 36]. The present study contributes to the body of literature describing self-reported race/ethnicity in patients with AD.

In this study, a quarter to a third of Asian and Other/Multiracial patients had early-onset AD, whereas almost three quarters of White patients experienced adult-onset AD. In addition, every race/ethnicity group had a higher percentage of patients with adult-onset AD compared with early-onset and childhood-onset AD. While it is surprising that a high number of patients reported adult-onset disease, a meta-analysis recently showed that the pooled proportion of adult-onset AD was 26.1% (CI 16.5–37.2%) [37]. The large percentage of late-onset AD patients in this study could also be explained by the fact that only adults were included in this study, as well as by recall bias — adult patients may not remember having had AD as an infant or child [38].

A moderate difference was identified based on participant work status, with the majority of participants employed full or part time. Notable differences included a larger percentage of students in the Asian population, a smaller percentage of disabled participants in the Asian population, and a higher percentage of retired participants in the White population. While it is difficult to specifically ascertain the consequences of differences in work status in this study, it is known that some occupations are higher risk for worsening of disease in individuals with AD [39]. Therefore, differences in occupations observed between racial/ethnic groups may be due to differences in severity of AD.

White patients were most often from the Midwest, whereas Black patients were most often from the South, and Asian, Other/Multiracial, and Hispanic/Latino patients were most often from the West. In a cross-sectional study using the Medical Expenditure Panel Survey, significant regional differences in race (p < 0.001) and ethnicity (p < 0.001) were observed where most Black patients were from South; however, most non-Hispanic patients were from the Midwest [40].

The proportion of Black patients insured by Medicaid was larger than other race/ethnicity groups. In addition, Hispanic and White patients had the highest percentage of private/commercial health insurance and White patients had the highest percentage of Medicare health insurance. It was shown that public health insurance, such as Medicaid or Medicare, is associated with poorer quality of life measures in AD [41]. Additionally, a study in Black patients reported that those with AD were more likely to use Medicaid insurance and that Medicaid insurance was one of the predictors of harmful financial impact due to out-of-pocket expenses [42].

Small differences were observed in the AD lesion locations at enrollment in palmar hands, plantar feet, face, and neck among race/ethnicity groups. In a study involving a Korean population, the head and neck was the most affected area of the body, followed by the upper extremities, lower extremities, and trunk [43]. In a cross-sectional, population-based study in US adults, lesions on the trunk were significantly more common in Blacks and Hispanics [44].

For clinical features examined in multivariable analysis, only two were identified as statistically significant: facial erythema and allergic shiners. Prevalence of facial erythema was statistically lower among Black patients vs White. It was reported that erythema in darker skin is more likely to be missed [22, 45], and Black patients have up to 6 times the risk of severe AD than White patients after adjusting for their erythema scores [22]. In addition, the use of common scoring systems that rely on skin erythema, including SCORAD and EASI, may underestimate the severity of AD in darker skin types; however, overall disease severity as measured by EASI, SCORAD, and v-IGA were not statistically different between groups [20, 46]. It is possible that measuring erythema may be more challenging in certain body regions. Prevalence of allergic shiners was higher among Blacks, Asians, and Other/Multiracial patients in the current study; this was previously reported in a few studies as a classic presentation of AD in African-American and Nigerian patients [20, 47]. Significant differences between race/ethnicity groups were not noted for the other clinical features analyzed in this study.

More severe EASI and SCORAD lichenification were observed in Black patients vs White patients. This is in congruence with previous studies in which African-American [20] and Nigerian patients [47] were more likely to develop lichenification than White patients. Severe SCORAD dryness was also observed in Black vs White patients. This could be hypothesized to be due to the findings that fewer filaggrin (FLG) gene repeats may lead to drier skin [48] and African-American patients with moderate-to-severe AD have low FLG monomer repeats [49]. Average pruritus over the last 7 days was also more significant in Black and Hispanic patients. Xerosis can certainly contribute to pruritus, but the literature also supports an increased risk of pruritus in Black individuals due to increased trans-epidermal water loss, increased size of mast cell granules, decreased ceramide levels and lower stratum corneum pH [50, 51].

There appear to be fewer data on Hispanic individuals and pruritus in the setting of AD in the literature; this may be an important unmet need to be addressed in future studies. In the current study, statistically more severe EASI lichenification (head and neck, trunk, lower extremities) and SCORAD lichenification were identified among Asian versus White patients. Previous studies showed that compared with Whites, Asians tend to have increased scaling and lichenification [18, 19].

Compared with White patients, Asian patients with moderate/severe vs none/mild signs of AD had a higher prevalence of moderate/severe EASI edema and lichenification in all areas and a higher prevalence of moderate/severe SCORAD swelling and lichenification. In patients with moderate/severe vs none/mild signs of AD, compared with White patients, Asian patients had a higher prevalence of moderate/severe EASI edema and lichenification in all areas and a higher prevalence of moderate/severe SCORAD swelling and lichenification. Black patients also had a higher prevalence of moderate/severe EASI lichenification in all areas, moderate/severe EASI edema in the lower extremities, and moderate/severe SCORAD lichenification compared with White patients.

This study did not identify race/ethnicity differences with regard to past history of systemic therapy for AD, but there was a small effect size for prior treatment with specifically systemic corticosteroids and phototherapy, with Asian and Other/Multiracial more likely to have used these. There was a small effect size difference for taking systemic therapy at study enrollment, with a greater proportion of Black, White, and Other/Multiracial patients taking systemic therapy at enrollment. There are limited studies on efficacy of AD treatments by race, ethnicity and/or skin type [27]; this is an area that requires further research.

This study was designed to assess the association of race/ethnicity with AD disease severity measures and PRO measures. These associations could be due to clinical, epidemiologic, and genetic differences among various race/ethnicity groups and may have clinical implications [48,49,50,51]. Currently, guidelines recommend a similar treatment approach across ethnic groups with subtle differences in skin phototype, genetics, and cultural practices [22]. However, as AD is a heterogeneous disease, it cannot be treated with one-size-fits-all approach. It is crucial to understand how these differences in phenotypes may affect therapeutic responses and influence selection of therapies. Clinical trials involved in the development of novel therapies should include diverse ethnic groups and subset analyses by race/ethnicity. Future studies should focus on assessing the underlying explanation for these observed associations.

Strengths and Limitations

The strength of this study lies with the large number of patients with AD deployed from the registry. This real-world study extensively assessed for phenotyping and patient-reported outcomes in a large dataset from diverse patient populations.

The CorEvitas AD Registry includes a sample of adults with AD that are not necessarily representative of all adults with AD in the US and Canada. The small numbers of patients who self-identify as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or as Multiracial did not allow for analysis of these individual race/ethnicity categories, due to limitations in estimation and statistical power. These patients were combined into a single group labeled “Other/Multiracial” for all analyses; thus, we were unable to make any inferences regarding these specific race/ethnicity groups. In the adjusted analysis, estimates were reported using the White race/ethnicity group as the reference category. We did not directly compare the disease severity and patient-reported measures between Blacks and Asians; however, we have compared Blacks and Asians with Whites. Future studies may compare the disease severity and patient-reported measures between Blacks and Asians.

Conclusion

In this analysis of real-world patients with AD, differences by race/ethnicity were observed in sociodemographic, clinical and treatment characteristics, disease severity, and PROs. Racial/ethnic differences were observed in EASI head and neck, upper and lower extremities lichenification, SCORAD lichenification and dryness, pruritus, and facial erythema and allergic shiners, even after accounting for potential confounders. Recognizing these variations may be of critical import for dermatologists for the design and delivery of targeted/personalized medicine approaches.