Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus

Kabashima, Kenji; Matsumura, Takayo; Komazaki, Hiroshi; Kawashima, Makoto

doi:10.1056/nejmoa1917006

Cited by 243 publications

(228 citation statements)

References 38 publications

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“…A phase-III follow-up extension study investigated Japanese adult patients with moderate-to-severe AD and pruritus treated with nemolizumab (60 mg, every 4 weeks) versus placebo over 16 weeks. 74 Here, nemolizumab reduced the median VAS score by 42.8% vs. placebo (21.4%, P<0.001). Mean EASI score, Dermatology Life Quality Index (DLQI) score also improved in nemolizumab group compared to the placebo group.…”

Section: Translational Importance Of Il-31 and Clinical Trialsmentioning

confidence: 76%

“…68 Several follow up studies demonstrated that blocking of IL31RA by a neutralizing antibody effectively prevented itch in AD mouse models and AD patients. [69][70][71][72][73][74] IL-31-dependent pruritic activity has been described in mice, canines, primates and humans despite the low inter-species homology of the cytokine. [75][76][77] Michels et al, demonstrated that subcutaneous administration of lokivetmab, a caninized anti-canine monoclonal anti-IL-31 antibody, alleviates itch symptoms in dogs with AD.…”

Section: Translational Importance Of Il-31 and Clinical Trialsmentioning

confidence: 99%

“…The importance of IL31RA in AD pathophysiology was demonstrated by early and recent trials validating a marked reduction in itch along with improvement of eczema, in some studies, in AD patients using anti-IL31RA antibody. 72,74,80 The success of these trials in moderate to severe AD suggests that sole blockage of the IL-31 pathway may be sufficient to achieve an acceptable therapeutic outcome in some patients. However, the success of the IL-4Rα-inhibiting antibody dupilumab in AD patients demands further evaluation how to stratify the heterogenous population of AD patients for the best 'personalized' benefit.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

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Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy

Datsi¹,

Alam²,

Faried³

et al. 2020

Preprint

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Interleukin-31 has been implicated in the pathophysiology of multiple atopic disorders such as atopic dermatitis (AD), rhinitis and airway hyperreactivity. In AD, IL-31 has been identified as one of the main ‘drivers’ of its cardinal symptom pruritus. Here, we aim to summarize the mechanisms by which IL-31 modulates inflammatory and allergic diseases. TH2 cells play a central role in AD and release high levels of TH2-produced cytokines including IL-31, thereby mediating inflammatory responses, initiating immunoregulatory circuits, and stimulating itch and neuronal outgrowth through activation of the heterodimer receptor IL-31 receptor alpha (IL31RA)/Oncostatin M receptor β. IL31RA expression is found on human and murine dorsal root ganglia neurons, epithelial cells including keratinocytes as well as various innate immune cells. IL-31 is a critical cytokine involved in neuro-immune communication, which opens new avenues for cytokine modulation in neuroinflammatory diseases including AD/pruritus, as validated by recent clinical trials using an anti-IL-31 antibody. Accordingly, inhibition of IL-31 downstream signaling may be a beneficial approach for various inflammatory diseases including prurigo nodularis. For example, whether downstream JAK inhibitors directly block IL-31-mediated-signaling needs to be clarified. Targeting the IL-31/IL31RA/OSMRβ axis appears to be a promising approach for inflammatory, neuroinflammatory and pruritic disorders in the future.

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Section: Translational Importance Of Il-31 and Clinical Trialsmentioning

confidence: 76%

Section: Translational Importance Of Il-31 and Clinical Trialsmentioning

confidence: 99%

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy

Datsi¹,

Alam²,

Faried³

et al. 2020

Preprint

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“…SCH is very useful to objectively show dryness and maintain the patient's motivation to moisturize. Although many new drugs for AD are expected to be developed in the future, 5 it is important to consider how long remission can be maintained after the treatment is finished. Therefore, we conclude that it is necessary to continue skin care instruction during and after the treatment of dupilumab.…”

Section: Dupilumab Probably Reduces Transepidermal Water Loss But Doementioning

confidence: 99%

Dupilumab probably reduces transepidermal water loss but does not increase stratum corneum hydration in atopic dermatitis

Furuhashi

Oda

Torii

et al. 2020

The Journal of Dermatology

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Dear Editor, Atopic dermatitis (AD) is a common and pruritic inflammatory skin disease, which has been widely treated by dupilumab. 1 It contributes to the treatment of adolescent AD patients with unmet high medical needs 2 and studies on the efficacy and safety in children as young as 6 years of age are in progress. 3 However, it is not yet known whether dupilumab restores skin barrier function in AD patients. Therefore, we investigated the extent to which skin barrier function was restored following treatment with dupilumab, using transepidermal water loss (TEWL) and stratum corneum hydration (SCH). A total of seven patients (aged 40.4 AE 15.8 years) and seven age-matched healthy volunteers (aged 35.4 AE 11.7 years) were enrolled in this study. Patients continued to use the same moisturizers

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“…As neuropathic itch can develop following neuroinflammatory injury, it is possible that some of the therapeutics shown to be helpful for atopic dermatitis might also benefit a subset of neuropathic itch patients. Once limited to barrier treatment, steroid creams, and anti-histamines, improved, specific treatments targeting cytokine mediators such as IL-4/IL-13 (dupilumab), IL-17 (secukinumab and ixekizumab), IL-31RA (nemolizumab), and JAK-STAT receptors have greatly improved patient outcomes [ 19 , 84 , 85 , 86 , 87 , 88 ]. Another drug class which has shown promise is neurokinin 1 (NK1) receptor antagonists.…”

Section: Future Therapeutic Directions For Neuropathic Itchmentioning

confidence: 99%

Neuropathic Itch

Meixiong

Dong

Weng

2020

Cells

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Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.

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Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus

Cited by 243 publications

References 38 publications

Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy

Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy

Dupilumab probably reduces transepidermal water loss but does not increase stratum corneum hydration in atopic dermatitis

Neuropathic Itch

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