In the context of new targeted therapies and the goal of precision medicine, stratification of patients based on their endotype is becoming increasingly important. Using the method of “deep phenotyping,” researchers were able to demonstrate correlations between elevated levels of the biomarkers IL-13, periostin, and dipeptidyl peptidase-4 with phenotypic features of atopic dermatitis.
Atopic dermatitis, one of the most common dermatoses, is often associated with significant distress and socioeconomic impact. This is also shown by a survey study with data from nine European countries, in which a total of 1189 patients with atopic eczema who were either under systemic treatment or eligible for systemic therapy participated. The study conducted in 2017-2018 showed that 57% of patients missed at least 1 day and 26% missed 6 or more days of work due to their skin disease (Fig. 1) [3]. The extent of absences from work due to illness correlated, among other things, with patients’ satisfaction with their system therapy. The less high this was, the more absences from work the affected persons had. This points to the importance of an optimal fit between systemic treatment and patient characteristics.
Endotyping as a basis for individually tailored therapy
The development of targeted therapies for moderate to severe atopic dermatitis has progressed rapidly in recent years. Given the large heterogeneity of phenotypes as well as the underlying molecular mechanisms – the endotype – individualized treatment approaches are most promising. IL-13 is a key cytokine in the pathophysiology of atopic dermatitis and induces the expression of periostin and dipeptidyl peptidase-4 (DPP-4), among others [1,2]. Patients with elevated levels of IL-13, periostin, and DPP-4 have been shown to respond better to system therapy with the anti-IL-13 antibody tralokinumab in both atopic dematitis (AD) and asthma.
Analysis with respect to the biomarkers IL-13, periostin and/or DPP-4.
Against this background, a research team led by Laura Maintz, MD, specialist at the Department of Dermatology and Allergology, University Hospital Bonn, conducted a study on deep phenotyping in AD patients with elevated IL-13, periostin and/or DPP-4 levels [2]. The investigators analyzed cross-sectional data from the Bonn CK-CARE-ProRaD cohort, which included 420 subjects ≥12 years of age without system therapy in the last month (active AD: n=373, nonatopic controls: n=47). Serum biomarkers collected were IL-13 (Olink proteomics), periostin, and DPP-4 (MesoScale).
Significant correlation with severity and other phenotype factors.
Statistical analysis showed that IL-13 and periostin correlated significantly with disease severity as measured by objective scores (EASI, BSA, SCORAD) and by patients’ subjective complaints such as pruritus, insomnia, dermatological quality of life (DLQI). It was found that 71.6% (73/102) of patients with moderate-severe AD (EASI ≥16) and 41% (111/271) with EASI <16 had increased levels of IL-13 alone or in combination with periostin or DPP-4. The most important predictive factors for the combined endotype of elevated serum levels of the biomarkers IL-13, periostin, and DPP-4 were disease severity, eosinophilia, elevated total IgE, and certain atopy sigmata and lifestyle factors (review 1). Analysis of the association of endotype with atopy sigmata is shown in Table 1. It was found that a subgroup of AD patients with elevated IL-13 levels, were significantly more frequently affected by Herthoge’s sign and maternal allergic rhinitis. Elevated serum levels of DPP-4 were associated with periorbital wiring, keratosis pilaris, perleche, and “dirty neck.”
Conclusion
The phenotypic predictors identified in the present study to identify patients who are likely to benefit most from IL-13 directed therapy is a very interesting finding with regard to optimized treatment concepts in terms of personalized medicine. “In summary, the different endotypes were associated with different phenotype factors,” she said. Of note was the high proportion of patients with elevated IL-13 levels even with an EASI<16. Elevated IL-13 levels were detected in half of the patients with EASI 7-16. This correlated with earlier disease onset, eosinophilia, and higher total IgE compared to the patient group with normative IL-13, raising the question of the presence of systemic inflammation below the current cut-off value for systemic therapy, she said. “Patients with mild-to-moderate atopic dermatitis (EASI 7-16) may also be potential candidates for systems therapy,” Dr. Maintz explains.
Congress: DDG Conference 2021
Literature:
- Bieber T: Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy 2020; 75(1): 54-62
- Maintz L, et al: Deep phenotyping of adolescent and adult patients with atopic dermatitis and elevated interleukin-13, periostin and/ or dipeptidyl peptidase-4 levels, FV01/09, DDG meeting, 04/15/2021.
- Zink AGS, et al: Out-of-pocket Costs for Individuals with Atopic Eczema: A Cross-sectional Study in Nine European Countries. Acta Derm Venereol 2019; 99(3): 263-267.
DERMATOLOGIE PRAXIS 2021; 31(5): 41-42 (published 7/10/21; ahead of print).
