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

Cro, S., Cornelius, V. R., Pink, A. E., Wilson, R., Pushpa-Rajah, A., Patel, P., Abdul-Wahab, A., August, S., Azad, J., Becher, G., Chapman, A., Dunnil, G., Ferguson, A. D., Fogo, A., Ghaffar, S. A., Ingram, J. R., Kavakleiva, S., Ladoyanni, E., Leman, J. A., Macbeth, A. E., Makrygeoegou, A., Parslew, R., Ryan, A. J., Sharma, A., Shipman, A. R., Sinclair, C., Wachsmuth, R., Woolf, R. T., Wright, A., McAteer, H., Barker, J. N. W. N., Burden, A. D., Griffiths, C. E. M., Reynolds, N. J., Warren, R. B., Lachmann, H. J., Capon, F. and Smith, C. H 2021. Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two staged, adaptive placebo controlled trial (APRICOT). British Journal of Dermatology 10.1111/bjd.20653
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Abstract

Background Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease affecting the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. Objective To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit for PPP. Methods A randomised (1:1), double-blind, two-staged, adaptive, UK multi-centre, placebo-controlled trial. Participants had a diagnosis of PPP (>6 months) requiring systemic therapy. Treatment was eight weeks of anakinra or placebo via daily self-administered subcutaneous injections. The primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Results A total of 374 patients were screened and 64 were enrolled (31 anakinra, 33 placebo) with mean baseline PPPASI 17.8 (SD=10.5); PPP investigator’s global assessment severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in intention-to-treat analysis, -1.65, 95% CI [-4.77 to 1.47], p=0.300. 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, similarly did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect (CACE) for an individual who receives ≥90% total treatment (48% anakinra group), was -3.80, 95% CI [-10.76 to 3.16], p=0.285. No serious adverse events occurred. Conclusions No evidence for superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Publisher: Wiley
ISSN: 0007-0963
Date of First Compliant Deposit: 28 September 2021
Date of Acceptance: 19 August 2021
Last Modified: 16 Oct 2021 07:09
URI: http://orca.cardiff.ac.uk/id/eprint/144495

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