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.
['Cro|Suzie|S|http://orcid.org/0000-0002-6113-1173', 'Smith|Catherine|C|', 'Wilson|Rosemary|R|', 'Cornelius|Victoria|V|']
D000075522:Adaptive Clinical Trials as Topic D003627:Data Interpretation, Statistical D003879:Dermatologic Agents D004311:Double-Blind Method D006801:Humans D053590:Interleukin 1 Receptor Antagonist Protein D011565:Psoriasis D016032:Randomized Controlled Trials as Topic D012720:Severity of Illness Index D012867:Skin D013997:Time Factors D016896:Treatment Outcome D014945:Wound Healing
Psoriasis Anakinra Statistical analysis plan Palmoplantar pustulosis Adaptive trial Randomised controlled trial