van de Kerkhof P, Guenther L, Gottlieb A B, Sebastian M, Wu J J, Foley P, Morita A, Goldblum O, Zhang L, Erickson J, Ball S, Rich P
Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Division of Dermatology, Department of Medicine, Western University, London, ON, Canada.
J Eur Acad Dermatol Venereol. 2017 Mar;31(3):477-482. doi: 10.1111/jdv.14033. Epub 2016 Dec 2.
Fingernail psoriasis is difficult to treat.
The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis.
This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept (50-mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160-mg starting dose. At Week 12, ixekizumab patients received open-label IXE Q4W through Week 60; placebo patients received a 160-mg starting ixekizumab dose and etanercept patients a 4-week placebo washout before starting IXE Q4W. Efficacy was assessed by mean per cent Nail Psoriasis Severity Index (NAPSI) improvement at Weeks 12 and 60.
Of 1346 patients in the UNCOVER-3 trial, this subgroup analysis included only patients with baseline fingernail psoriasis: 116 (60.1%) placebo, 236 (61.8%) etanercept, 228 (59.1%) IXE Q4W and 229 (59.5%) IXE Q2W. At Week 12, greater mean per cent NAPSI improvements were achieved in IXE Q4W (36.7%) and IXE Q2W (35.2%) vs. placebo (-34.3%, P < 0.001 each comparison) and etanercept (20.0%, P = 0.048 vs. Q4W, P = 0.072 vs. Q2W). At Week 60, mean per cent NAPSI improvement was >80% regardless of initial treatment. At Week 12 (nonresponder imputation), complete resolution (NAPSI = 0) was achieved in 19.7% (IXE Q4W), 17.5% (IXE Q2W), 4.3% (placebo, P < 0.001 each comparison) and 10.2% (etanercept, P < 0.05 each comparison) of patients. By Week 60, >50% of patients achieved complete resolution.
At Week 12, significant improvements in fingernail psoriasis were achieved with ixekizumab therapy. With IXE Q4W maintenance dosing, additional improvement was demonstrated through 60 weeks, and >50% of patients achieved complete resolution. Registered at clinicaltrials.gov: NCT01646177.
指甲银屑病难以治疗。
评估选择性靶向白细胞介素-17A的单克隆抗体司库奇尤单抗对指甲银屑病的疗效。
这项3期双盲试验（UNCOVER-3）将患者随机分为安慰剂组、依那西普组（每周两次，每次50毫克）或司库奇尤单抗组，司库奇尤单抗起始剂量为160毫克，之后每4周（IXE Q4W）或每2周（IXE Q2W）注射80毫克。在第12周时，司库奇尤单抗组患者接受开放标签的IXE Q4W治疗直至第60周；安慰剂组患者接受160毫克的司库奇尤单抗起始剂量，依那西普组患者在开始IXE Q4W治疗前接受4周的安慰剂洗脱期。通过第12周和第60周指甲银屑病严重程度指数（NAPSI）改善的平均百分比来评估疗效。
在UNCOVER-3试验的1346例患者中，该亚组分析仅纳入了基线时有指甲银屑病的患者：安慰剂组116例（60.1%），依那西普组236例（61.8%），IXE Q4W组228例（59.1%），IXE Q2W组229例（59.5%）。在第12周时，IXE Q4W组（36.7%）和IXE Q2W组（35.2%）的NAPSI改善平均百分比显著高于安慰剂组（-34.3%，每次比较P<0.001）和依那西普组（20.0%，与Q4W组比较P = 0.048，与Q2W组比较P = 0.072）。在第60周时，无论初始治疗如何，NAPSI改善平均百分比均>80%。在第12周（对无反应者进行估算），19.7%（IXE Q4W组）、17.5%（IXE Q2W组）、4.3%（安慰剂组，每次比较P<0.001）和10.2%（依那西普组，每次比较P<0.05）的患者实现了完全缓解（NAPSI = 0）。到第60周时，>50%的患者实现了完全缓解。
在第12周时，司库奇尤单抗治疗使指甲银屑病有显著改善。采用IXE Q4W维持给药，在60周内显示出进一步改善，且>50%的患者实现了完全缓解。在clinicaltrials.gov注册：NCT01646177。
