Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 19;186(2):245-256.
doi: 10.1111/bjd.20653. Online ahead of print.

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

S Cro  1 , V R Cornelius  1 , A E Pink  2 , R Wilson  2 , A Pushpa-Rajah  2 , P Patel  2 , A Abdul-Wahab  3 , S August  4 , J Azad  5 , G Becher  6 , A Chapman  7 , G Dunnil  8 , A D Ferguson  9 , A Fogo  10 , S A Ghaffar  11 , J R Ingram  12 , S Kavakleiva  13 , E Ladoyanni  14 , J A Leman  15 , A E Macbeth  16 , A Makrygeoegou  6 , R Parslew  17 , A J Ryan  18 , A Sharma  19 , A R Shipman  20 , C Sinclair  21 , R Wachsmuth  22 , R T Woolf  2 , A Wright  23 , H McAteer  24 , J N W N Barker  25 , A D Burden  26 , C E M Griffiths  27 , N J Reynolds  28 , R B Warren  29 , H J Lachmann  29 , F Capon  30 , C H Smith  2 ; APRICOT Study Group
Affiliations

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

S Cro et al. Br J Dermatol. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
CONSORT flow chart. ITT, intention to treat. aTwo participants were randomized in error and were subsequently found to be ineligible. They were not offered treatment and were immediately withdrawn from the study, and excluded from all analyses. bOne participant withdrew from the trial in week 1. One participant was lost to follow‐up and withdrawn after week 4. cOne participant withdrew at week 8. Numbers withdrawn from the trial are cumulative.
Figure 2
Figure 2
(a) Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI); (b) fresh pustule count; (c) total pustule count; and (d) Dermatology Life Quality Index (DLQI) over the 12‐week follow‐up period. Error bars represent 95% confidence intervals.
Figure 3
Figure 3
Adverse events by MedDRA (Medical Dictionary for Regulatory Activities) system organ class. CI, confidence interval.
See this image and copyright information in PMC

Comment in

References

    1. Navarini AA, Burden AD, Capon F et al. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol 2017; 31:1792–9. - PubMed
    1. National Health Service Psoriasis – overview. Available at: https://www.nhs.uk/conditions/psoriasis/ (last accessed 29 October 2020).
    1. Griffiths CE, Christophers E, Barker JN et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol 2007; 156:258–62. - PubMed
    1. Bhutani T, Patel T, Koo B et al. A prospective, interventional assessment of psoriasis quality of life using a nonskin‐specific validated instrument that allows comparison with other major medical conditions. J Am Acad Dermatol 2013; 69:e79–88. - PubMed
    1. Sampogna F, Gisondi P, Melchi CF et al. Prevalence of symptoms experienced by patients with different clinical types of psoriasis. Br J Dermatol 2004; 151:594–9. - PubMed