Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Via Alessandro Manzoni 113, Rozzano-Milan, 20089, Italy.
Skin Pathology Laboratory, IRCCS Istituto Clinico Humanitas, Via Alessandro Manzoni 113, Rozzano-Milan, 20089, Italy.
Br J Dermatol. 2018 Nov;179(5):1072-1080. doi: 10.1111/bjd.16705. Epub 2018 Aug 14.
Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers.
To evaluate the efficacy and safety of secukinumab 300 mg in HLA-Cw6-positive (Cw6-POS) and HLA-Cw6-negative (Cw6-NEG) patients with moderate-to-severe chronic plaque-type psoriasis.
SUPREME was a 24-week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks.
In total, 434 patients were recruited: 185 (42·6%) were Cw6-POS and 246 (56·7%) were Cw6-NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6-POS 42·7 ± 13·1; Cw6-NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6-POS 20·7 ± 8·99; Cw6-NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6-POS and 79·7% of Cw6-NEG patients (difference 0·76; 95% confidence interval -7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6-POS 1·36 ± 3·58; Cw6-NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment-emergent adverse events [Cw6-POS 42·7%; Cw6-NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI.
Determination of HLA-Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA-Cw6 status.
了解遗传变异对于预测治疗反应很重要，并且是确定银屑病治疗新的药物遗传学和药物基因组学靶点的基础。关于司库奇尤单抗与遗传标志物的疗效相关数据有限。
评估司库奇尤单抗 300mg 在 HLA-Cw6 阳性（Cw6-POS）和 HLA-Cw6 阴性（Cw6-NEG）中重度慢性斑块型银屑病患者中的疗效和安全性。
SUPREME 是一项为期 24 周的 IIIb 期研究，延长至 72 周。主要终点是 16 周后达到银屑病面积严重程度指数（PASI）90 缓解率。
共纳入 434 例患者：185 例（42.6%）为 Cw6-POS，246 例（56.7%）为 Cw6-NEG（3 例未评估）。平均（±SD）年龄为 45.2±13.2 岁（Cw6-POS：42.7±13.1；Cw6-NEG：47.2±12.9）。两组基线 PASI 评分相当[Cw6-POS：20.7±8.99；Cw6-NEG：21.5±9.99（P=0.777）]。第 16 周时，80.4%的 Cw6-POS 患者和 79.7%的 Cw6-NEG 患者达到 PASI90（差异 0.76；95%置信区间-7.04 至 8.23）。第 16 周时，绝对 PASI 无显著差异（Cw6-POS：1.36±3.58；Cw6-NEG：1.18±2.29）。司库奇尤单抗的总体安全性与先前报道一致。治疗中出现的不良事件发生率无统计学差异[Cw6-POS：42.7%；Cw6-NEG：49.6%（P=0.295）]。司库奇尤单抗治疗可实现较高的 PASI90 缓解率，且绝对 PASI 快速降低。
对于司库奇尤单抗治疗，确定 HLA-Cw6 状态是不必要的，因为无论 HLA-Cw6 状态如何，它都具有高度的疗效。
