用阿那白滞素治疗脓疱性银屑病：一项适应性两阶段随机安慰剂对照试验第 1 阶段的统计分析计划。

Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial.

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 and Kings College London, 9th Floor Tower Wing, Guy's Hospital, London, SE1 9RT, UK.

出版信息

Trials. 2018 Oct 3;19(1):534. doi: 10.1186/s13063-018-2914-y.

DOI:10.1186/s13063-018-2914-y

PMID:30285894

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6169096/

Abstract

BACKGROUND

Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease. It is known to affect quality of life at a level comparable to that from major medical and psychiatric illness, yet current treatment options are remarkably limited. Recent evidence however suggests that interleukin-1 (IL-1) blockade with anakinra will deliver therapeutic benefit in PPP.

METHODS

Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) is a two-staged, adaptive, double-blind, randomised placebo-controlled trial which aims to test the hypothesis that IL-1 blockade with anakinra will deliver therapeutic benefit in PPP. During stage 1 a total of 24 patients will be randomised (1:1) to receive either placebo or anakinra. The two candidate primary outcomes are fresh pustule count (across palms and soles) and the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score, recorded at baseline and at weeks 1, 4 and 8. Analysis at the end of stage 1 will compare treatment arms to ensure sufficient efficacy and safety in order to progress to stage 2. The primary outcome for stage 2 will also be identified following an assessment of the reliability and discriminative ability of fresh pustule count and PPPASI. The trial is powered to detect efficacy and will recruit an additional 40 patients in stage 2 (n = 64 in total). Analysis will follow the intention-to-treat principle and analyse patients as randomised.

DISCUSSION

This manuscript describes the important features of the small population trial design for APRICOT and the pre-specified statistical analysis plan for stage 1. The statistical analysis plan has been developed prior to data extraction and in compliance with international guidelines. It will increase the transparency of the data analysis for the APRICOT trial. The findings of the trial will help to clarify the role of anakinra in the treatment of PPP.

TRIAL REGISTRATION

ISCRTN, ISCRTN13127147 . Registered on 1 August 2016. EudraCT Number 2015-003600-23 . Registered on 1 April 2016.

摘要

背景

掌跖脓疱病（PPP）是一种罕见的慢性炎症性皮肤病。已知它会对生活质量产生影响，程度可与重大的医疗和精神疾病相媲美，但目前的治疗选择却非常有限。然而，最近的证据表明，白细胞介素-1（IL-1）阻滞剂阿那白滞素在 PPP 中具有治疗作用。

方法

阿那白滞素治疗脓疱性银屑病：对照试验的反应（APRICOT）是一项两阶段、适应性、双盲、随机、安慰剂对照试验，旨在检验阿那白滞素阻断 IL-1 是否会对 PPP 产生治疗作用的假设。在第一阶段，共有 24 名患者将被随机（1:1）分为接受安慰剂或阿那白滞素。两个候选的主要结局是新鲜脓疱计数（手掌和足底）和掌跖脓疱病面积和严重程度指数（PPPASI）评分，分别在基线、第 1、4 和 8 周记录。在第一阶段结束时的分析将比较治疗组，以确保有足够的疗效和安全性，从而进入第二阶段。第二阶段的主要结局也将在评估新鲜脓疱计数和 PPPASI 的可靠性和区分能力后确定。该试验有足够的效能来检测疗效，将在第二阶段招募另外 40 名患者（总共 64 名患者）。分析将遵循意向治疗原则，并按随机分组分析患者。