Specific targeting of interleukin-23p19 as effective treatment for psoriasis

Levin, Adriane A.; Gottlieb, Alice B.

doi:10.1016/j.jaad.2013.10.043

Cited by 58 publications

(42 citation statements)

References 61 publications

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“…IL-23 induces development of Th17 cells and secretion of IL-17 [22]. IL-17 causes neutrophil influx and is involved in neutrophil-mediated inflammatory responses [23]; IL-17 mRNA levels (assessed by quantitative PCR) in lesional skin samples of psoriasis have been found to be higher in pustular psoriasis than in other clinical subtypes [23]; this may explain why ustekinumab has been successfully used once in generalized pustular psoriasis [24]; moreover, it has been shown that successful treatment of generalized pustular psoriasis by infliximab + acitretin was followed by a marked reduction of IL-12 and IL-23 expression in the skin (evaluated by immunohistochemistry) [25].…”

Section: Discussionmentioning

confidence: 99%

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Saunier¹,

Debarbieux²,

Jullien

et al. 2014

Dermatology

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Acrodermatitis continua of Hallopeau (ACH) is a rare form of chronic acral pustular eruption. Considered to be a variant of pustular psoriasis, it is a refractory condition that may not respond to conventional treatments. We report herein the case of a 53-year-old patient whose ACH was refractory to all conventional systemic treatment modalities and to anti-tumour necrosis factor. Because he had increased plasma levels of interleukin (IL)-1β, he received anakinra for 7 weeks, without further improvement however. Achievement of complete response was obtained with ustekinumab 90 mg s.c. every 12 weeks combined with acitretin; the plasma level of IL-1β concomitantly returned to normal. This case report is associated with a review on recent data on ACH treatment with biological agents, including anakinra and ustekinumab.

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Section: Discussionmentioning

confidence: 99%

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Saunier¹,

Debarbieux²,

Jullien

et al. 2014

Dermatology

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“…Efficacy comparable to blocking of the IL-12/23 axis has been shown in mouse models of psoriasis and multiple sclerosis 80. Available emerging data in psoriasis suggest that selective blockade of IL-23 may be critical in the pathogenesis of psoriasis more so than combined IL-12/23 blockade 81.…”

Section: Specific Il-23 Inhibitionmentioning

confidence: 99%

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Deepak¹,

Loftus²

2016

DDDT

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Crohn’s disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI) for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn’s disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn’s disease.

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“…Th17 cells are involved in the pathogenesis of autoimmune diseases and chronic inflammatory disorders (6), and targeting of IL-23 has become a promising strategy in these disorders (7).…”

mentioning

confidence: 99%

Non-Canonical Interleukin 23 Receptor Complex Assembly

Schröder

Moll

Baran

et al. 2015

Journal of Biological Chemistry

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Background:The heterodimeric cytokine IL-23 binds to a receptor complex consisting of IL-23R and IL-12R␤1. Results: Binding of IL-23 to IL-12R␤1 is mediated by domains 1 and 2 of p40. Conclusion:The IL-23⅐IL-23R⅐IL-12R␤1 complex formation does not follow the classical "site I-II-III" architectural paradigm. Significance: The p40 subunit is shared by IL-23 and IL-12 and interacts directly with IL-12R␤1.

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Specific targeting of interleukin-23p19 as effective treatment for psoriasis

Cited by 58 publications

References 61 publications

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Non-Canonical Interleukin 23 Receptor Complex Assembly

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Specific targeting of interleukin-23p19 as effective treatment for psoriasis

Cited by 58 publications

References 61 publications

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Acrodermatitis Continua of Hallopeau Treated Successfully with Ustekinumab and Acitretin after Failure of Tumour Necrosis Factor Blockade and Anakinra

Ustekinumab in treatment of Crohn&rsquo;s disease: design, development, and potential place in therapy

Non-Canonical Interleukin 23 Receptor Complex Assembly

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Product

Resources

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Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy