@article{e96cf93111764ffb9eb78cee7ff4076d,
title = "Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT)",
abstract = "Background: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. Objectives: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. Methods: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Results: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator{\textquoteright}s global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [–1·65, 95% confidence interval (CI) –4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI –26·44 to 32·33; favouring anakinra), total pustule count (–30·08, 95% CI –83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was –3·80 (95% CI –10·76 to 3·16; P = 0·285). No serious adverse events occurred. Conclusions: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.",
author = "{the APRICOT Study Group} and S. Cro and Cornelius, {V. R.} and Pink, {A. E.} and R. Wilson and A. Pushpa-Rajah and P. Patel and A. Abdul-Wahab and S. August and J. Azad and G. Becher and A. Chapman and G. Dunnil and Ferguson, {A. D.} and A. Fogo and Ghaffar, {S. A.} and Ingram, {J. R.} and S. Kavakleiva and E. Ladoyanni and Leman, {J. A.} and Macbeth, {A. E.} and A. Makrygeoegou and R. Parslew and Ryan, {A. J.} and A. Sharma and Shipman, {A. R.} and C. Sinclair and R. Wachsmuth and Woolf, {R. T.} and A. Wright and H. McAteer and Barker, {J. N.W.N.} and Burden, {A. D.} and Griffiths, {C. E.M.} and Reynolds, {N. J.} and Warren, {R. B.} and Lachmann, {H. J.} and F. Capon and Smith, {C. H.}",
note = "Funding Information: We would like to thank all the patients who participated in APRICOT and who made this study possible. We thank the independent members of the APRICOT Trial Steering Committee (Professor Edel O{\textquoteright}Toole, Professor Herv{\'e} Bachelez, Dr Stephen Kelly and Mr David Britten) and the Data Monitoring Committee (Professor Deborah Symmons, Dr Mike Ardern‐Jones and Professor Simon Skene. We thank Giselle Folloni, who was a passionate advocate for the study on social media. We thank Emma Gray and Aysar Al‐Rawi, who were the study{\textquoteright}s Clinical Research Associates. We thank Ange Cape and the Guy{\textquoteright}s Hospital Pharmacy Manufacturing Unit for processing, labelling and coordinating distribution of the study{\textquoteright}s investigational medicinal product. We thank Caroline Murphy and the King{\textquoteright}s Clinical Trials Unit for their assistance with developing the electronic case report form and for their support in delivering the trial. We thank the Psoriasis Association for their ongoing support since the inception of this project and throughout. The APRICOT Team acknowledges the support of the National Institute for Health Research Clinical Research Network (NIHR CRN). The study was developed with support from the UK Dermatology Clinical Trials Network (UK DCTN). The UK DCTN is grateful to the British Association of Dermatologists and the University of Nottingham for their financial support of the network. This study was supported by the United Kingdom Clinical Research Collaboration‐registered King{\textquoteright}s Clinical Trials Unit at King{\textquoteright}s Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London, and the NIHR Evaluation, Trials and Studies Coordinating Centre. Thank you to the BADBIR (British Association of Dermatologists Biologic and Immunomodulators Register) pharmacovigilance team for providing MedDRA coding for adverse events. MedDRA (the Medical Dictionary for Regulatory Activities) terminology is the international medical terminology developed under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). MedDRA trademark is registered by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) on behalf of ICH. This report presents independent research commissioned by the NIHR. The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the National Health Service, the NIHR, the Medical Research Council, the NIHR Central Commissioning Facility, NIHR Evaluation, Trials and Studies Coordinating Centre, the NIHR Efficacy and Mechanism Evaluation programme or the Department of Health. {\textregistered} {\textregistered} {\textregistered} Publisher Copyright: {\textcopyright} 2021 British Association of Dermatologists",
year = "2021",
month = oct,
day = "12",
doi = "10.1111/bjd.20653",
language = "English",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "John Wiley & Sons, Ltd (10.1111)",
}