Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism

Guttman‐Yassky, Emma; Ungar, Benjamin; Noda, Shinichi; Suprun, Maria; Shroff, Anjali; Dutt, Riana; Khattri, Saakshi; Min, Michelle; Mansouri, Yasaman; Zheng, Xiuzhong; Estrada, Yeriel; Singer, Giselle; Suárez‐Fariñas, Mayte; Krueger, James G.; Lebwohl, Mark

doi:10.1016/j.jaci.2015.11.001

Cited by 79 publications

(75 citation statements)

References 9 publications

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“…162 In a small phase II study 163 using the FDA-approved psoriasis dosing, ustekinumab had clear and sustained clinical and molecular effects, 163 but outcomes (as compared to the “placebo” arm) were likely obscured by the allowed background topical glucocorticosteroid use, 21 and waning treatment effects after 8–10 weeks from each ustekinumab administration, suggesting under-dosing of the drug. Interestingly, ustekinumab treatment in AD 163 and alopecia areata patients 164 induced significant reductions in Th2 axis, in addition to the expected reductions in Th1, Th17 and Th22 axes.…”

Section: Targeted Therapies As Milestones In Understanding Pathogenesismentioning

confidence: 88%

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

Brunner

Guttman‐Yassky

Leung

2017

Journal of Allergy and Clinical Immunology

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Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of Th22, Th17/IL-23 and Th1 cytokine pathways, depending on the subtype of the disease. In this review, we discuss our current understanding of the AD immune map in both early-onset as well as chronic disease. Clinical studies using broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD, as non-lesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients suffering from moderate-to-severe disease.

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Section: Targeted Therapies As Milestones In Understanding Pathogenesismentioning

confidence: 88%

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

Brunner

Guttman‐Yassky

Leung

2017

Journal of Allergy and Clinical Immunology

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500

461

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“…The authors concluded that treatment efficacy was due to blocking of IL-23 signaling [48], however ustekinumab also inhibits IL-12, which may stimulate IFN-γ production. It is therefore possible the treatment response was primarily due to interfering with the IFN-γ signaling.…”

Section: Future Management Strategies: Proofs Of Conceptmentioning

confidence: 99%

Understanding autoimmunity of vitiligo and alopecia areata

Rork

Rashighi²,

Harris³

2016

Current Opinion in Pediatrics

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Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.

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“…Suárez-Fariñas et al reported a highly increase of PDE4 in human AA lesions in their study [12]. In a furher study by Guttman-Yassky et al, levels of PDE4 were found to decrease after treatment with IL-12/IL-23 antagonist [92].…”

Section: Apremilastmentioning

confidence: 87%

“…At the 20th week, all patients exhibited varying degrees of hair regrowth. The patient with AU, with the highest baseline inflammation and lowest expression of hair keratins, exhibited the highest regrowth [92].…”

Section: Ustekinumabmentioning

confidence: 97%

New Modalities in the Treatment of Refractory Alopecia Areata

Kılıç¹

2017

Hair and Scalp Disorders

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Alopecia areata (AA) is a common and complex T-cell-mediated inflammatory disorder. It may be patchy (localized), involve the entire scalp (alopecia totalis) or entire body (alopecia universalis). Alopecia totalis and universalis are often difficult to treat. Although many therapeutic options currently exist in alopecia areata, none of them are curative or preventive. Besides, none of them are approved by Food and Drug Administration (FDA). The disease unfortunately has an unpredictable course. The factors indicating a poor prognosis are the extent of hair loss at the presentation, long duration of the disease, and ophiasis pattern of hair loss. There are only a few randomized controlled studies conducted on recalcitrant AA. Recent research on immunology of hair follicle and recent developments in immunopathogenesis, together with the shared pathways of the disease with other autoimmune disorders, led investigators to focus on novel therapies that target specific immunological pathways. Herein, we will review shortly the current treatment options in recalcitrant alopecia areata based on recently published studies and then will focus on the recently developed broad-spectrum and targeted therapeutics.

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Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism

Cited by 79 publications

References 9 publications

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

Understanding autoimmunity of vitiligo and alopecia areata

New Modalities in the Treatment of Refractory Alopecia Areata

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