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

https://doi.org/10.1016/j.jaci.2014.01.025Get rights and content
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Background

IL-23 expression is increased in psoriatic lesions and might regulate TH17 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 total of 24 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 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 [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.

Key words

Histology
IL-23
gene expression
guselkumab
psoriasis
Psoriasis Area and Severity Index
serum
skin
T cell
TH17

Abbreviations used

AE
Adverse event
DC
Dendritic cell
IL-12Rβ1
IL-12 receptor β1
IL-23R
IL-23 receptor
KRT16
Keratin 16
LCN2
Lipocalin 2
PASI
Psoriasis Area and Severity Index
PASI 75
75% improvement in PASI score from baseline
PASI 90
90% improvement in PASI score from baseline

Cited by (0)

Supported by Janssen Research & Development, LLC.

Disclosure of potential conflict of interest: H. Sofen has received consulting fees or honoraria from Janssen; was provided writing assistance, medicines, equipment, or administrative support from Janssen; and has received payment for lectures from Janssen, Amgen, Abbvie, Novartis, Pfizer, and Lilly. S. Smith has received research support from Janssen and has received payment for lectures from Janssen and Abbvie. R. T. Matheson has received research support from Janssen. C. L. Leonardi has consultant arrangements with Abbvie/Abbott, Amgen, Centocor/Janssen, Eli Lilly, Leo Pharmaceuticals, and Pfizer; has received payment for lectures from Amgen and Abbvie/Abbott; and has received fees for service for conducting clinical trials from Abbott, Amgen, Anacor, Celgene, Centocor/Janssen, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Maruho, Merck, Pfizer, Schering-Plough, Sirtris, Stiefel, Leo, Novartis, Tolmar, Novo Nordisk, Vascular Biogenics, Warner Chilcott, and Wyeth. C. Calderon, C. Brodmerkel, K. Li, K. Campbell, Y. Wasfi, Y. Wang, and P. Szapary are employed by Janssen (Johnson & Johnson) and have stock/stock options from Johnson & Johnson. S. J. Marciniak is employed by Janssen. J. Krueger has consultant arrangements with Pfizer, Centocor/Janssen, and Lilly and has received research support from Pfizer, Amgen, Centocor/Janssen, Lilly, and Merck.