Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives.

Abstract:

:The development of ustekinumab as a first-in-class anti-interleukin (IL) 12/23p40 therapeutic agent for psoriasis represents an important example of modern and rational drug design and development. Psoriasis is a chronic, systemic, immune-mediated skin disorder with considerable clinical, psychosocial, and economic burden. Ustekinumab is a human monoclonal antibody (mAb) that binds the p40 subunit common to IL-12 and IL-23, key cytokines in psoriasis pathogenesis. The therapeutic mAb was developed using human gamma-1 immunoglobulin (IgG)-expressing transgenic mice, which created a molecule with endogenous IgG(1) biologic properties and low immunogenicity. Ustekinumab was well tolerated in clinical studies and yielded rapid, significant, and sustained efficacy plus improved quality of life/work performance and reduced depression/anxiety. Its pharmacologic properties afford the most convenient dosing regimen among approved biologics, representing a significant advancement in the treatment of moderate to severe psoriasis. Ustekinumab also holds promise for other immune-mediated disorders with significant unmet need.

journal_name

Ann N Y Acad Sci

authors

Yeilding N,Szapary P,Brodmerkel C,Benson J,Plotnick M,Zhou H,Goyal K,Schenkel B,Giles-Komar J,Mascelli MA,Guzzo C

doi

10.1111/j.1749-6632.2011.05963.x

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

30-9

eissn

0077-8923

issn

1749-6632

journal_volume

1222

pub_type

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