title: HLA-C*06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program.
abstract: Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs. 76%, respectively, achieved at least a 75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] at week 24). A modestly higher proportion of HLA-C*06:02-positive than HLA-C*06:02-negative patients achieved PASI 75/90 responses at weeks 12 and 24. The largest response difference between the positive and negative patients (17.9%) was observed for PASI 75 (week 12), with smaller differences noted at later time points for PASI 90 (11.8% at week 24) and PASI 100 (10.2% at week 28). A differential response to ustekinumab has been confirmed in HLA-C*06:02-positive versus HLA-C*06:02-negative patients; however, this difference is modest, particularly at the higher response rate thresholds (PASI 90/100) and later time points (weeks 24/28).
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Li
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: C Chris
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Randazzo
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Szapary
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Curran
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. Electronic address: CBrodmer@its.jnj.com.
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D002648:Child; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015236:HLA-C Antigens / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D011379:Prognosis; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D018570:Risk Assessment; D012737:Sex Factors; D016896:Treatment Outcome; D000069549:Ustekinumab / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D053759:Interleukin-23; D000069549:Ustekinumab