Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

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

Authors: Victoria Cornelius, Rosemary Wilson, Suzie Cro, Jonathan Barker, David Burden, Christopher E. M. Griffiths, Helen Lachmann, Helen McAteer, Nick Reynolds, Andrew Pink, Richard B. Warren, Francesca Capon, Catherine Smith

Published in: Trials | Issue 1/2018

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
Navarini AA, Burden AD, Capon F, Mrowietz U, Puig L, Köks S, Kingo K, Smith C, Barker JN, ERASPEN Network. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792–9.CrossRef
2.
Sampogna F, Gisondi P, Melchi CF, Amerio P, Girolomoni G, Abeni D, IDI Multipurpose Psoriasis Research on Vital Experiences Investigators. Prevalence of symptoms experienced by patients with different clinical types of psoriasis. Br J Dermatol. 2004;151(3):594–9.CrossRef
3.
Farley E, Masrour S, McKey J, Menter A. Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009;60(6):1024–31.CrossRef
4.
Sampogna F, Tabolli S, Soderfeldt B, Axtelius B, Aparo U, Abeni D; IDI Multipurpose Psoriasis Research on Vital Experiences Investigators. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol. 2006;154(5):844–849.CrossRef
5.
Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, Ding J, Li Y, Tejasvi T, Gudjonsson JE, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44(12):1341–8.CrossRef
6.
Bissonnette R, Nigen S, Langley RG, Lynde CW, Tan J, Fuentes-Duculan J, Krueger JG. Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial. J Eur Acad Dermatol Venereol. 2014;28(10):1298–305.CrossRef
7.
8.
Marsland AM, Chalmers RJ, Hollis S, Leonardi-Bee J, Griffiths CE. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2006;1:CD001433.
9.
Smith CH, Jabbar-Lopez ZK, Yiu ZZ, Bale T, Burden AD, Coates LC, Cruickshank M, Hadoke T, MacMahon E, Murphy R, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628–636. https://​doi.​org/​https://​doi.​org/​10.​1111/​bjd.​15665.CrossRef
10.
Li M, Han J, Lu Z, Li H, Zhu K, Cheng R, Jiao Q, Zhang C, Zhu C, Zhuang Y, et al. Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized pustular psoriasis and psoriasis vulgaris. J Invest Dermatol. 2013;133(11):2637–9.CrossRef
11.
Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V, Knight J, Spain SL, Nestle FO, Burden AD, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet. 2011;89(3):432–7.CrossRef
12.
Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, Zribi J, Bal E, Cluzeau C, Chrabieh M, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(7):620–8.CrossRef
13.
Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, Bossuyt X, Boutten A, Bienvenu J, Duquesne A, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54.CrossRef
14.
Balow JE Jr, Ryan JG, Chae JJ, Booty MG, Bulua A, Stone D, Sun HW, Greene J, Barham B, Goldbach-Mansky R, et al. Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. Ann Rheum Dis. 2013;72(6):1064–70.CrossRef
15.
Viguier M, Guigue P, Pages C, Smahi A, Bachelez H. Successful treatment of generalized pustular psoriasis with the interleukin-1-receptor antagonist anakinra: lack of correlation with IL1RN mutations. Ann Intern Med. 2010;153(1):66–7.CrossRef
16.
Huffmeier U, Watzold M, Mohr J, Schon MP, Mossner R. Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol. 2014;170(1):202–4.CrossRef
17.
Rossi-Semerano L, Piram M, Chiaverini C, De Ricaud D, Smahi A, Kone-Paut I. First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics. 2013;132(4):e1043–7.CrossRef
18.
Lutz V, Lipsker D. Acitretin- and tumor necrosis factor inhibitor-resistant Acrodermatitis continua of Hallopeau responsive to the interleukin 1 receptor antagonist anakinra. Arch Dermatol. 2012;148(3):297–9.CrossRef
19.
Tauber M, Viguier M, Alimova E, Petit A, Liote F, Smahi A, Bachelez H. Partial clinical response to anakinra in severe palmoplantar pustular psoriasis. Br J Dermatol. 2014;171(3):646–9.CrossRef
20.
Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7.CrossRef
21.
Bhushan M, Burden AD, McElhone K, James R, Vanhoutte FP, Griffiths CE. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2001;145(4):546–53.CrossRef
22.
Finlay AY, Khan GK. Dermatology life quality index (DLQI)—a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–6.CrossRef
23.
EuroQol G. EuroQol – a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208.CrossRef
24.
Lassus A, Geiger JM. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Br J Dermatol. 1988;119(6):755–9.CrossRef
25.
Bland JM, Altman DG. Agreement between methods of measurement with multiple observations per individual. J Biopharm Stat. 2007;17(4):571–82.CrossRef
26.
Parmar MK, Sydes MR, Morris TP. How do you design randomised trials for smaller populations? A framework. BMC Med. 2016;14:183.CrossRef
Metadata
Title
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
Authors
Victoria Cornelius
Rosemary Wilson
Suzie Cro
Jonathan Barker
David Burden
Christopher E. M. Griffiths
Helen Lachmann
Helen McAteer
Nick Reynolds
Andrew Pink
Richard B. Warren
Francesca Capon
Catherine Smith
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2841-y

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Open-label randomized controlled trial to compare wound dressings for patients undergoing hip and knee arthroplasty: study protocol for a randomized controlled trial

Commentary

New guidance to improve sample size calculations for trials: eliciting the target difference

Study protocol

Electronic nicotine devices to aid smoking cessation by alcohol- and drug-dependent clients: protocol for a pilot randomised controlled trial

Study protocol

Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial

Study protocol

Twenty weeks of isometric handgrip home training to lower blood pressure in hypertensive older adults: a study protocol for a randomized controlled trial

Study protocol

Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial