Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).
Suzie Cro,Victoria Cornelius,Andrew Pink,Rosemary Wilson,A. Pushpa-Rajah,Prakash Patel,A. Abdul-Wahab,Suzannah August,J Azad,G. Becher,A. Chapman,G. Dunnil,A.D. Ferguson,A. Fogo,S.A. Ghaffar,John R. Ingram,S. Kavakleiva,E. Ladoyanni,J.A. Leman,A. E. Macbeth,A. Makrygeoegou,R Parslew,Anthony J. Ryan,Anil Sharma,Alexa R. Shipman,C. Sinclair,R. Wachsmuth,R T Woolf,Andrew Wright,H. McAteer,Jonathan Barker,A D Burden,Christopher E.M. Griffiths,Nick J. Reynolds,R.B. Warren,Helen J. Lachmann,Francesca Capon,Catherine H. Smith +37 more
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In this article, anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in Pustulosis (PPP) using a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial.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.read more
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Journal ArticleDOI
Pustular Psoriasis: From Pathophysiology to Treatment
Giovanni Genovese,Chiara Moltrasio,Nicoletta Cassano,Carlo Alberto Maronese,Gino A. Vena,Angelo V. Marzano +5 more
TL;DR: Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base as discussed by the authors.
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IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications
Helena Iznardo,Lluís Puig +1 more
TL;DR: Treatment targeting of IL-1 pathways has been studied, and several monoclonal antibodies are currently being assessed in clinical trials, and promising results have been obtained with anti-IL-36R spesolimab and imsidolimAB in pustular psoriasis, and their efficacy is being tested in other conditions.
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Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis.
Danielle McCluskey,Natashia Benzian-Olsson,Satveer K. Mahil,Nina Karoliina Hassi,Christian Wohnhaas,A. David Burden,Christopher E.M. Griffiths,John R. Ingram,Nick J. Levell,R Parslew,Andrew Pink,Nick J. Reynolds,Richard B. Warren,Sudha Visvanathan,Patrick Baum,Jonathan Barker,Catherine H. Smith,Francesca Capon +17 more
TL;DR: In this paper , the authors applied bulk and single-cell RNA sequencing (RNA-Seq) methods to the analysis of skin biopsy samples and peripheral blood mononuclear cells.
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Anakinra for Refractory Pustular Psoriasis: A Phase II, Open Label, Dose-Escalation Trial.
Haley B. Naik,Dominique C. Pichard,Daniella M. Schwartz,Michelle O'Brien,Matthew Masciocchi,Julie D. Thompson,H. Nida Sen,Seth M. Steinberg,Sandra A. Mitchell,Adriana Almeida de Jesus,Timothy H. McCalmont,A. K. Dubey,Rachel Rosenstein,Zuoming Deng,Raphaela Goldbach-Mansky,Nehal N. Mehta,Edward W. Cowen +16 more
TL;DR: Mostafa A. Dand N. Smolen et al. as mentioned in this paper evaluated the recombinant IL-1Ra anakinra for pustular psoriasis and characterized extracutaneous disease manifestations.
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Eliminating Ambiguous Treatment Effects Using Estimands
TL;DR: In this paper , an estimand is defined as a clear description of what the treatment effect represents, thus saving readers the necessity of trying to infer this from study methods and potentially getting it wrong.
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