Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis

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• 作者：Howard Sofen ; MD^a ; Stacy Smith ; MD^b ; Robert T. Matheson ; MD^c ; Craig L. Leonardi ; MD^d ; Cesar Calderon ; PhD^e ; Carrie Brodmerkel ; PhD^e ; Katherine Li ; MS^e ; Kim Campbell ; PhD^e ; Stanley J. Marciniak Jr. ; MBA^e ; Yasmine Wasfi ; MD ; PhD^e ; Yuhua Wang ; PhD^e ; Philippe Szapary ; MD^e ; James G. Krueger ; MD ; PhD^f ; ^{jgk@rockefeller.edu" class="auth_mail}
• 关键词：Histology ; IL-23 ; gene expression ; guselkumab ; psoriasis ; Psoriasis Area and Severity Index ; serum ; skin ; T cell ; TH17
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：April, 2014
• 年：2014
• 卷：133
• 期：4
• 页码：1032-1040
• 全文大小：2924 K

文摘

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Background

IL-23 expression is increased in psoriatic lesions and might regulate T_H17 T-cell counts in patients with psoriasis.

Objectives

We sought to test a novel IL-23-specific therapeutic agent for the treatment of psoriasis.

Methods

In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti-IL-23-specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A聽total of 24聽patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients.

Results

At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all聽guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4聽[50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients.

Conclusion

IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.