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

Cro, S. et al. (2022) Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT). British Journal of Dermatology, 186(2), pp. 245-256. (doi: 10.1111/bjd.20653) (PMID:34411292)

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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’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.

Item Type:Articles
Additional Information:This project is funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership (NIHR EME 13/ 50/17 APRICOT). The study drug and placebo were supplied by Swedish Orphan Biovitrum (SOBI). In addition, funding from the Psoriasis Association (RG2/10) is acknowledged. Support for the study was received from the Department of Health via the NIHR BioResource Clinical Research Facility and comprehensive Biomedical Research Centre awards to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust (guysbrc-2012-1). C.E.M.G. and R.B.W. are supported, in part, by the NIHR Manchester Biomedical Research Centre. N.J.R. is supported, in part, by the NIHR Newcastle Biomedical Research Centre, the NIHR Newcastle In Vitro Diagnostics Co-operative and is a NIHR Senior Investigator. APRICOT is an investigatorled project.
Keywords:Dermatology
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: 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.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:British Journal of Dermatology
Publisher:Wiley
ISSN:0007-0963
ISSN (Online):1365-2133
Published Online:19 August 2021
Copyright Holders:Copyright © 2021 The Author(s)
First Published:First published in British Journal of Dermatology 186(2): 245-256
Publisher Policy:Reproduced under a Creative Commons License

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