HLA-C*06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program

• DOI: 10.1016/j.jid.2016.06.631
• Publication Date: 2016-07-30T01:24:54Z
• Authors: Katherine Li; C. Chris Huang; Bruce Randazzo; Shu Li; Philippe Szapary; Mark Curran; Kim Campbell; Carrie Brodmerkel
• Keywords: Adult; Male; Adolescent; Dermatology; HLA-C Antigens; Biochemistry; Interleukin-23; Risk Assessment; Drug Administration Schedule; 03 medical and health sciences; Sex Factors; 0302 clinical medicine; Double-Blind Method; Confidence Intervals; Humans; Psoriasis; Molecular Targeted Therapy; Child; Molecular Biology; Alleles; Analysis of Variance; Dose-Response Relationship, Drug; Age Factors; Cell Biology; Prognosis; 3. Good health; Female

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).