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

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 center dot 8 (10 center dot 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 center dot 65, 95% confidence interval (CI) -4 center dot 77 to 1 center dot 47; P = 0 center dot 30]. Similarly, secondary objective measures, including fresh pustule count (2 center dot 94, 95% CI -26 center dot 44 to 32 center dot 33; favouring anakinra), total pustule count (-30 center dot 08, 95% CI -83 center dot 20 to 23 center dot 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 center dot 80 (95% CI -10 center dot 76 to 3 center dot 16; P = 0 center dot 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.