title: 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.
authors: Centocor Research and Development, Inc., Malvern, Pennsylvania 19087, USA. nyeildin@its.jnj.com
authors: Newman
authors: N
authors: Yeilding
authors: Philippe
authors: P
authors: Szapary
authors: Carrie
authors: C
authors: Brodmerkel
authors: Jacqueline
authors: J
authors: Benson
authors: Michael
authors: M
authors: Plotnick
authors: Honghui
authors: H
authors: Zhou
authors: Kavitha
authors: K
authors: Goyal
authors: Brad
authors: B
authors: Schenkel
authors: Jill
authors: J
authors: Giles-Komar
authors: Mary Ann
authors: MA
authors: Mascelli
authors: Cynthia
authors: C
authors: Guzzo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015195:Drug Design; D055808:Drug Discovery / Q000639:trends; D005544:Forecasting; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000276:immunology; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D011565:Psoriasis / Q000188:drug therapy*; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D053759:Interleukin-23; D018664:Interleukin-12; D000069549:Ustekinumab