一项确定阿那白滞素治疗脓疱型银屑病疗效的小样本、随机、安慰剂对照试验：APRICOT试验研究方案
A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial.
作者信息
Cornelius Victoria, Wilson Rosemary, Cro Suzie, Barker Jonathan, Burden David, Griffiths Christopher E M, Lachmann Helen, McAteer Helen, Reynolds Nick, Pink Andrew, Warren Richard B, Capon Francesca, Smith Catherine
机构信息
Imperial Clinical Trials Unit, School of Public Health, Imperial College London, Stadium House, 68 Wood Lane, London, W12 7RH, UK.
St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, 9th Floor Tower Wing, Guy's Hospital, London, UK.
出版信息
Trials. 2018 Aug 29;19(1):465. doi: 10.1186/s13063-018-2841-y.
BACKGROUND
Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis.
METHODS/DESIGN: We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2.
DISCUSSION
We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis.
TRIAL REGISTRATION
ISRCTN13127147 . Registered on 1st August 2016. EudraCT, 2015-003600-23 . Registered on 1st April 2016.
背景
掌跖脓疱病是一种罕见但疼痛且使人衰弱的疾病。在所有银屑病表型变体中，就症状和功能损害而言，它始终排名最高。在过去10年中，随着生物疗法的出现，斑块型银屑病的治疗发生了革命性变化，但脓疱型银屑病的治疗选择仍然极为有限。基于提示白细胞介素（IL）-1在脓疱型银屑病中起关键致病作用的机制研究结果，我们推测阿那白滞素（IL-1阻断剂）将是脓疱型银屑病的有效治疗方法。
方法/设计：我们将进行一项两阶段、适应性、双盲、随机、安慰剂对照试验，以检验以下假设：阿那白滞素通过皮下注射每日自行给药，持续8周，将对掌跖脓疱病（脓疱型银屑病的一种局限性形式，通常累及手掌和/或脚底）产生治疗益处。将收集20周的安全性结果。总共64名参与者将按1:1的比例随机分配至阿那白滞素组或安慰剂组。在第1阶段结束时，将做出是否进入第2阶段的决定。该决定将在24名参与者被随机分组并随访8周后做出，且将基于两个治疗组中观察到的平均结果值的排序。在第1阶段结束时，还将评估结果测量的可靠性和数据收集方法，并为第2阶段确认主要结果。
讨论
我们采用了一种适应性方法，即在完成一项有足够效力的疗效试验之前获取概念验证数据，因为脓疱型银屑病是一种罕见疾病，不存在用于检测变化的经过验证的结果测量方法，且该人群中阿那白滞素的安全性数据有限。据我们所知，这将是第一项随机对照试验，将为IL-1阻断剂治疗脓疱型银屑病的疗效和安全性提供有价值的证据。
试验注册
ISRCTN13127147。于2016年8月1日注册。EudraCT，2015-003600-23。于2016年4月1日注册。
Zotero 插件