Efficacy and safety of mepolizumab administered subcutaneously for moderate to severe atopic dermatitis

Kang, Eunhye; Narayana, Poornima Krishnamurthy; Pouliquen, Isabelle; Lopez, Monica C.; Ferreira‐Cornwell, M. Celeste; Getsy, John

doi:10.1111/all.14050

Cited by 44 publications

(29 citation statements)

References 9 publications

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“…A marginal potential bene t was suggested in terms of disease activity in the study with the higher dosing regimen, but exposure to treatment was too short to allow any meaningful conclusions in such a chronic and spontaneously uctuating disease (203). The impact of treatment on tissue eosinophilia was not assessed, nor was the possibility that treatment could reduce occurrence of disease ares rather than baseline disease activity (NCT03055195) (204). The role of lymphocytes, mast cells, and other cells in the immune pathology may be more signi cant than that of eosinophils in pathogenesis of this complex disorder.…”

Section: Eosinophilic Skin Diseasementioning

confidence: 99%

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Jacobsen

Jackson

Heffler

et al. 2021

Annu. Rev. Immunol.

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The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Eosinophilic Skin Diseasementioning

confidence: 99%

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Jacobsen

Jackson

Heffler

et al. 2021

Annu. Rev. Immunol.

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“…Mepolizumab is a fully-humanized monoclonal anti-IL-5 antibody approved for the treatment of severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis 53 . In a phase 2 study, there was no meaningful difference in IGA and NRS score with placebo group 54 .…”

Section: Il-5 Inhibitionmentioning

confidence: 92%

Therapeutic New Era for Atopic Dermatitis: Part 1. Biologics

2021

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Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.

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“…A recently published placebo-controlled study indicated the efficacy of mepolizumab in patients with moderate to severe AD, demonstrating the improvement of clinical scores in patients treated with subcutaneously administered mepolizumab. 47 Thus, future studies with anti-IL-5 or anti-IL-5R may yield additional positive results. The role of eosinophils has been studied in bullous autoimmune dermatoses, such as pemphigus (involving autoantibodies against desmosomal proteins) and pemphigoid (involving auto-antibodies against adhesion proteins).…”

Section: Eosinophilic Skin Diseasesmentioning

confidence: 99%