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

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.