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HLA - C*06:02 等位基因与对白细胞介素 - 12/23 抑制的反应:优特克单抗 3 期银屑病项目的结果

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

作者信息

Li Katherine, Huang C Chris, Randazzo Bruce, Li Shu, Szapary Philippe, Curran Mark, Campbell Kim, Brodmerkel Carrie

机构信息

Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.

Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.

出版信息

J Invest Dermatol. 2016 Dec;136(12):2364-2371. doi: 10.1016/j.jid.2016.06.631. Epub 2016 Jul 29.

Abstract

Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C06:02 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-C06:02-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-C06:02-positive than HLA-C06:02-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-C06:02-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).

摘要

多项小型研究表明,人类白细胞抗原(HLA)-Cw6(C06:02)等位基因的存在可能是乌司奴单抗治疗反应改善的一个预测指标。本研究旨在评估在乌司奴单抗治疗中重度银屑病的3期研究的大量患者队列中,HLA-C06:02等位基因与乌司奴单抗治疗反应之间的关联。在这项回顾性研究中,HLA-C06:02阳性和阴性患者对乌司奴单抗均表现出良好反应(分别为86%和76%,在第24周时银屑病面积和严重程度指数[PASI 75]较基线至少改善75%)。在第12周和第24周时,达到PASI 75/90反应的HLA-C06:02阳性患者比例略高于HLA-C06:02阴性患者。阳性和阴性患者之间最大的反应差异(17.9%)出现在PASI 75(第12周),在后期时间点,PASI 90(第24周时为11.8%)和PASI 100(第28周时为10.2%)的差异较小。已证实HLA-C06:02阳性与HLA-C*06:02阴性患者对乌司奴单抗的反应存在差异;然而,这种差异较小,尤其是在较高反应率阈值(PASI 90/100)和后期时间点(第24/28周)。

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