Investigating Real-World Effectiveness of Disease-Modifying Therapies in AD by Skin Type

Dupilumab may provide an improved reduction in atopic dermatitis (AD) severity for patients with dark vs light skin types, according to findings of a study published in JAAD International.

AD is one of the most common dermatological conditions with a greater prevalence shown in black and mixed race populations. Researchers note that differences seem to exist between AD in darkly pigmented and light skin, including variations in genetics and immunology, with inherent structural properties in dark skin potentially triggering pruritus through higher transepidermal water loss and an increased size of mast cells.

“This may imply a potential biological basis for differences in treatment response between light and dark skin. Studies investigating the effectiveness and safety of systemic therapy in patients with AD of different skin types are lacking, and only a few studies focus on this topic,” said the study authors.

They sought to investigate the effectiveness and safety of systemic therapies, including dupilumab, ciclosporin and methotrexate, in people with AD of different skin types, as well as the association between morphological phenotypes and skin types in patients.

An observational prospective cohort study was conducting using pooled real-world data from the Dutch TREAT (TREatment of ATopic eczema) NL and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register) registries. Eligible patients were all children and adults with AD from 2 centers in the Netherlands (November 2017 to June 2020) and 13 centers in the United Kingdom (October 2018 to April 2021) who started treatment with dupilumab, ciclosporin and/or methotrexate in the context of routine clinical care.

Study visits were performed at baseline, 4 weeks, and then approximately every 3 months, alongside routine clinic appointments. Light skin types were defined as Fitzpatrick skin types 1-3, and dark skin types as Fitzpatrick skin types 4-6.

Effectiveness was analyzed using the Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS) peak pruritus past 24 hours, Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI) or Infants' Dermatitis Quality of Life Index (IDQLI). Safety was assessed through the reporting of adverse events at each visit.

“Baseline scores were compared to treatment endpoint scores using paired t-tests. To investigate differences between treatment groups in delta scores and the course of scores over time, we used linear mixed-effects models with an interaction between time and treatment,” explained researchers.

“We included a random intercept for each patient and, in addition to skin type, included variables for which we found a significant difference between dark skin type and light skin type in the models as potential confounders (including age, baseline severity score, follicular eczema, allergic contact dermatitis, and previous phototherapy use).”

A total of 235 patients were included, of which 156 individuals had light skin types (ethnicity; White, 94.2%) and 68 had dark skin types (ethnicity; Black African/Afro-Caribbean, 25%; South Asian, 26.5%; Hispanics, 0%). Patients with dark skin types were noted to be younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline EASI scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008).

After accounting for covariates, including baseline EASI, patients with dark skin types showed greater mean EASI reduction vs those with light skin types between baseline and 6 months with dupilumab (16.7 vs 9.7; adjusted P = .032).

No difference in EASI improvement was found between dark and light skin types for methotrexate and ciclosporin, as well as no difference in any of the other scores for all treatments. Moreover, no differences were found for adverse events for any treatments (P > .05), as well as for treatment discontinuation between the 2 groups (P > .05).

Regarding differences in morphological phenotypes, a higher prevalence of follicular eczema was shown in patients with dark vs light skin types (22.1% vs 2.6%; P < .001).

“Larger studies are needed to confirm these results, and skin type should therefore be considered a confounder in future AD intervention studies,” they concluded. “Further research investigating whether morphological phenotypes respond differently to treatments is needed.”

Reference

Bosma AL, Ouwerkerk W, Heidema MJ, et al. Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types. JAAD Int. Published online October 10, 2022. doi:10.1016/j.jdin.2022.09.006