Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials

Yang, Xiaoliang; Kambe, Naotomo; Takimoto‐Ito, Riko; Kabashima, Kenji

doi:10.1016/j.pharmthera.2021.107830

Cited by 29 publications

(25 citation statements)

References 104 publications

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“…However, the situation has changed dramatically in recent years because various molecularly targeted drugs have been used to treat moderate-to-severe AD (Figure 2) (Yang et al, 2021). These drugs not only improve skin rashes but are also effective in eliminating pruritus.…”

Section: Cytokine-mediated Pruritus In Admentioning

confidence: 99%

A New Era with the Development of Cytokine-Based Therapy for Pruritus

Shibuya

Takimoto‐Ito

Kambe

et al. 2022

Journal of Investigative Dermatology

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Section: Cytokine-mediated Pruritus In Admentioning

confidence: 99%

A New Era with the Development of Cytokine-Based Therapy for Pruritus

Shibuya

Takimoto‐Ito

Kambe

et al. 2022

Journal of Investigative Dermatology

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“…Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by exacerbations and remissions of intensely itchy eczema. In recent years, better understanding of the pathogenesis of AD allowed to improve treatment strategies with many emerging therapeutic options 1–3 . Type 2 inflammation, pruritus, and impaired skin barrier function are prominently involved in the pathogenesis of AD 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it was hoped that topical anti‐inflammatory products other than TCS and TCI would be available. In recent years, Phase III clinical trials of topical treatments for AD have been conducted with PDE4 inhibitors(crisaborole,) and JAK inhibitors (delgocitinib [DEL], tofacitinib and ruxolitinib) 1–3 . Among these new topical treatments, DEL ointment was recently licensed in Japan.…”

Section: Introductionmentioning

confidence: 99%

Real‐world efficacy of proactive maintenance treatment with delgocitinib ointment twice weekly in adult patients with atopic dermatitis

Suehiro

Numata

Murakami

et al. 2022

Dermatologic Therapy

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Previous studies have shown the efficacy of delgocitinib (DEL) ointment, a topical Janus kinase inhibitor, against atopic dermatitis (AD). However, there is no available information regarding the efficacy of DEL ointment in maintaining remission. Data of patients with AD who received remission maintenance therapy twice weekly with DEL or topical corticosteroid (TCS) on the affected skin of each upper limb were extracted from the medical records. Efficacy was assessed based on changes in pruritus numerical rating scale (NRS) score, stratum corneum hydration (SCH), erythema index (EI). Of 25 patients, four patients (16%) had eczema flare‐ups on the TCS side and eight patients (32%) on the DEL side. The extent of change in each parameter between TCS‐ and DEL‐treated areas of the skin did not differ significantly. The mean changes in the NRS and EI showed a slight improvement on the side treated with TCS and were slightly worse on the side treated with DEL. However, the SCH of the DEL group was maintained, while that of the TCS group worsened. TCS is more likely to be effective than DEL in terms of remission maintenance therapy. However, topical DEL is as effective as topical steroid in the maintenance therapy of AD in dry skin patients.

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“…4,9 The cytokines that are responsible for the debilitating manifestations of AD and for maintaining the underlying pathogenic immunological conditions of the disease are attractive targets for therapeutic intervention. 10 The activity of cytokines related to AD and other autoimmune diseases can be inhibited by different means, e.g., by preventing the binding of the cytokines to their cognate cellsurface expressed receptors by cytokine-specific monoclonal antibodies (mAbs). 11 mAbs targeting proinflammatory cytokines have been successfully used for systemic treatment of atopic skin conditions including AD 11 but the use of mAbs for topical administration has not been widely successful due to the challenges of formulation and delivery.…”

Section: Introductionmentioning

confidence: 99%

“…The cytokines that are responsible for the debilitating manifestations of AD and for maintaining the underlying pathogenic immunological conditions of the disease are attractive targets for therapeutic intervention 10 . The activity of cytokines related to AD and other autoimmune diseases can be inhibited by different means, e.g., by preventing the binding of the cytokines to their cognate cell‐surface expressed receptors by cytokine‐specific monoclonal antibodies (mAbs) 11 .…”

Section: Introductionmentioning

confidence: 99%

Clinical effect of delgocitinib 0.5% ointment on atopic dermatitis eczema intensity and skin barrier function

Abe¹,

Iizuka²,

Nemoto-Hasebe³

et al. 2021

J Cutaneous Imm & Allergy

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Objectives Delgocitinib is a small‐molecule JAK inhibitor that has recently been approved in Japan as the world's first topical JAK/STAT pathway inhibitor for the treatment of atopic dermatitis (AD). In this study, the effects of delgocitinib 0.5% ointment treatment on skin rash severity and skin‐barrier function were examined. Methods Adult Japanese patients with mild‐moderate AD (n = 23) were recruited into the trial. Healthy subjects (n = 10) were examined in parallel. The effects of four weeks of treatment with delgocitinib 0.5% ointment on the partial eczema area and severity index (pEASI) score, stratum corneum hydration (SCH), and trans‐epidermal water‐loss (TEWL) were examined. Patient reported effects of the treatment were assessed by a questionnaire. Results Four weeks of treatment showed a statistically significant improvement (p < .001) in pEASI score of 61.8%, ±54.0 (mean%, SD) compared to baseline in AD patients. Improvement in SCH at four weeks (37.6AU, ±11.5 (mean, SD), p < .001) was achieved in AD patients compared to baseline (SCH = 24.9AU, ±8.8 (mean, SD)). A trend toward reduction in TEWL over time was seen in the active treatment group (TEWL = 9.1 g/h/m2 at baseline, 7.1 g/h/m2 at two weeks, and 6.9 g/h/m2 at 4 weeks). The pEASI score and SCH and TEWL values improved from two‐to‐four weeks treatment. Patients reported perceived improvements after four weeks of treatment on all parameters associated with skin condition. No safety concerns were identified. Conclusions Treatment with delgocitinib 0.5% ointment was well tolerated and showed improvements of both eczema and SCH in adult AD patients.

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Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials

Cited by 29 publications

References 104 publications

A New Era with the Development of Cytokine-Based Therapy for Pruritus

A New Era with the Development of Cytokine-Based Therapy for Pruritus

Real‐world efficacy of proactive maintenance treatment with delgocitinib ointment twice weekly in adult patients with atopic dermatitis

Clinical effect of delgocitinib 0.5% ointment on atopic dermatitis eczema intensity and skin barrier function

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