title: Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.
abstract: BACKGROUND
  IL-23 expression is increased in psoriatic lesions and might regulate TH17 T-cell counts in patients with psoriasis.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine/Dermatology, UCLA School of Medicine, Los Angeles, Calif.
authors.forename: Howard
authors.initials: H
authors.lastname: Sofen
authors.affiliation: Dermatology, San Diego, Calif.
authors.forename: Stacy
authors.initials: S
authors.lastname: Smith
authors.affiliation: Oregon Medical Research Center, Portland, Ore.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Matheson
authors.affiliation: Department of Dermatology, St Louis University, St Louis, Mo.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Leonardi
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Cesar
authors.initials: C
authors.lastname: Calderon
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Katherine
authors.initials: K
authors.lastname: Li
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Kim
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Marciniak
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Wasfi
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pa.
authors.forename: Philippe
authors.initials: P
authors.lastname: Szapary
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address: jgk@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D001706:Biopsy; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood; D053759:Interleukin-23 / Q000037:antagonists & inhibitors*; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; C000588857:guselkumab
keywords: Histology; IL-23; Psoriasis Area and Severity Index; T cell; T(H)17; gene expression; guselkumab; psoriasis; serum; skin