Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis

Abstract

Background: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. Objectives: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. Methods: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. Results: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. Conclusion: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

The impact of dupilumab on skin barrier function: A systematic review

“…The dose of dupilumab used in five of them was the one recommended in the datasheet (a subcutaneous injection of dupilumab 300 mg every other week following a loading dose of 600 mg Dupilumab dose). Only Berdyshev et al used a different dose in patients with weight below 60 kg: a loading dose of 400 mg with subsequent doses of 200 mg. Two researches did not include any comparison group 16,17 and three articles included healthy individuals as the comparison group 15,18,19 . Only one study compared the impact of dupilumab on skin barrier function with other treatments, including topical corticosteroids and cyclosporine.…”

“…Patients with AD have high TEWL values reflecting skin barrier dysfunction. It is important to restore skin barrier and decrease local and systemic inflammation for a successful management of AD 17 . Ceramide emollients and topical treatments, including corticosteroids and calcineurin inhibitors, decrease TEWL improving skin barrier in patients with AD 30–32 .…”

“…It is important to restore skin barrier and decrease local and systemic inflammation for a successful management of AD. 17 Ceramide emollients and topical treatments, including corticosteroids and calcineurin inhibitors, decrease TEWL improving skin barrier in patients with AD. [30][31][32] Topical corticosteroids improve clinical inflammatory features and reduce TEWL by decreasing IL-13 production and upregulating filaggrin and loricrin expression.…”

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

“…Some other studies have also evaluated the impact of dupilumab on skin barrier function [ 46 , 47 , 48 , 49 , 50 ]. They showed that dupilumab reduced TEWL on non-involved and involved skin [ 46 , 47 , 48 , 49 , 50 ]. The impact of dupilumab in SCH differs between studies.…”

Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases

“…Epidermal barrier dysfunctions in the lesional and nonlesional skin of patients is a critical feature of AD; these dysfunctions result in a greater transepidermal water loss (TEWL) and also a decrease in skin hydration [ 110 , 111 ].…”