Bissonnette R, Nigen S, Langley R G, Lynde C W, Tan J, Fuentes-Duculan J, Krueger J G
Innovaderm Research Inc., Montreal, QC, Canada.
J Eur Acad Dermatol Venereol. 2014 Oct;28(10):1298-305. doi: 10.1111/jdv.12272. Epub 2013 Sep 24.
Palmo-plantar pustular psoriasis (PPPP) and palmo-plantar pustulosis (PPP) are chronic skin diseases with significant impact on quality of life.
The purpose of this study was to study the efficacy of ustekinumab in PPPP and PPP and gain more knowledge on the pathophysiology and the role of the interleukin-23 (IL-23) signalling pathway in these diseases.
Thirty-three patients with either PPPP (20) or PPP (13) and seven volunteers with normal palmo-plantar skin were recruited. Patients with PPP or PPPP were randomised (1 : 1) to receive either an anti IL-12/IL-23 antibody (ustekinumab 45 mg) or placebo at day 0 and week 4 with subsequent placebo cross-over to ustekinumab at week 16. The primary endpoint was the proportion of patients randomized to ustekinumab achieving a 50% improvement in the Palmo-Plantar Pustular Area and Severity Index (PPPASI-50) as compared to placebo. Skin biopsies of the palms and soles of normal subjects and patients with PPP or PPPP were performed and analysed by RT-PCR and immunohistochemistry.
There was no statistically significant difference in the proportion of patients randomised to ustekinumab as compared to those randomised to placebo achieving PPPASI-50 at week 16 for patients with PPPP (10%, 20%; P = 1.000) or PPP (20%, 37.5%; P = 1.000) respectively. Compared to normal subjects an 89-fold increase in IL-17A expression was found in palms/soles of patients with PPPP (P = 0.006) and a 190-fold increase for patients with PPP (P = 0.051). There were no statistically significant changes in cytokine expression at week 16 in the palms and soles of patients with PPP or PPPP.
Taken together these results suggest that ustekinumab at a dose of 45 mg has limited efficacy in PPPP and PPP. IL-17A may have a more important role than IL-23 in patients with PPPP and PPP. Conclusions are limited by the small sample size of this study.
掌跖脓疱型银屑病（PPPP）和掌跖脓疱病（PPP）是对生活质量有重大影响的慢性皮肤病。
本研究旨在探讨优特克单抗治疗PPPP和PPP的疗效，并进一步了解这些疾病的病理生理学以及白细胞介素-23（IL-23）信号通路的作用。
招募了33例PPPP患者（20例）或PPP患者（13例）以及7名掌跖皮肤正常的志愿者。PPP或PPPP患者被随机分组（1:1），在第0天和第4周接受抗IL-12/IL-23抗体（优特克单抗45mg）或安慰剂治疗，随后在第16周安慰剂交叉换用优特克单抗。主要终点是与安慰剂相比，随机接受优特克单抗治疗的患者在掌跖脓疱面积和严重程度指数（PPPASI-50）上改善50%的患者比例。对正常受试者以及PPP或PPPP患者的手掌和脚底进行皮肤活检，并通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学进行分析。
对于PPPP患者（10%，20%；P = 1.000）或PPP患者（20%，37.5%；P = 1.000），在第16周时，随机接受优特克单抗治疗的患者与随机接受安慰剂治疗的患者达到PPPASI-50的比例无统计学显著差异。与正常受试者相比，PPPP患者手掌/脚底的IL-17A表达增加了89倍（P = 0.006），PPP患者增加了190倍（P = 0.051）。PPP或PPPP患者手掌和脚底在第16周时细胞因子表达无统计学显著变化。
综合这些结果表明，45mg剂量的优特克单抗在PPPP和PPP中的疗效有限。在PPPP和PPP患者中，IL-17A可能比IL-23发挥更重要的作用。本研究样本量小，结论有限。
