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Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT)

Lookup NU author(s): Professor Nick ReynoldsORCiD



This is the final published version of an article that has been published in its final definitive form by John Wiley and Sons Inc., 2022.

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© 2021 British Association of Dermatologists. 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’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.

Publication metadata

Author(s): Cro S, Cornelius VR, Pink AE, Wilson R, Pushpa-Rajah A, Patel P, Abdul-Wahab A, August S, Azad J, Becher G, Chapman A, Dunnil G, Ferguson AD, Fogo A, Ghaffar SA, Ingram JR, Kavakleiva S, Ladoyanni E, Leman JA, Macbeth AE, Makrygeoegou A, Parslew R, Ryan AJ, Sharma A, Shipman AR, Sinclair C, Wachsmuth R, Woolf RT, Wright A, McAteer H, Barker JNWN, Burden AD, Griffiths CEM, Reynolds NJ, Warren RB, Lachmann HJ, Capon F, Smith CH

Publication type: Article

Publication status: Published

Journal: British Journal of Dermatology

Year: 2022

Volume: 186

Issue: 2

Pages: 245-256

Print publication date: 01/02/2022

Online publication date: 19/08/2021

Acceptance date: 14/07/2021

Date deposited: 24/02/2022

ISSN (print): 0007-0963

ISSN (electronic): 1365-2133

Publisher: John Wiley and Sons Inc.


DOI: 10.1111/bjd.20653

PubMed id: 34411292


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