Anakinra for palmoplantar pustulosis: results from a randomized, double‐blind, multicentre, two‐staged, adaptive placebo‐controlled trial (APRICOT)*
Suzie Cro, Victoria Cornelius, Andrew Pink, Rebecca Wilson, Angela Pushpa‐Rajah, Prakash A. Patel, Alya Abdul‐Wahab, S. August, J. Azad, G Becher, Anna Chapman, Giles Dunnill, Adam Ferguson, A. Fogo, S.A. Ghaffar, John R Ingram, Svetlana Kavakleiva, E. Ladoyanni, Joyce Leman, A. E. Macbeth, Areti Makrygeorgou, Richard Parslew, Alan J. Ryan, Amit Sharma, Alexa R. Shipman, Catriona Sinclair, Rachel Wachsmuth, Richard Woolf, Andrew Wright, Helen McAteer, Juliet N. Barker, A. David Burden, C.E.M. Griffiths, Nick J. Reynolds, Richard B. Warren, Helen J. Lachmann, Francesca Capon, Catherine Smith, the APRICOT Study Group, Davide Altamura, Vincent Piguet, Roberto Verdolini, Marc Wallace, Kavitha Sundararaj, Nisha Arujuna, Charlotte Fleming, Ruth Lamb, J. H. Dodds, Sonia Baryschpolec, Hywel Cooper
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.