Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
19 Aug 2021
19 Aug 2021
Historique:
accepted:
14
07
2021
pubmed:
20
8
2021
medline:
20
8
2021
entrez:
19
8
2021
Statut:
aheadofprint
Résumé
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. To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. 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. 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. No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.
Sections du résumé
BACKGROUND
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
OBJECTIVE
To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP.
METHODS
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
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
CONCLUSIONS
No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.
Identifiants
pubmed: 34411292
doi: 10.1111/bjd.20653
pmc: PMC9255857
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Efficacy and Mechanism Evaluation Programme
ID : NIHR EME 13/50/17 APRICOT
Organisme : The Psoriasis Association
ID : RG2/10
Organisme : 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
ID : guysbrc-2012-1
Organisme : Swedish Orphan Biovitrum
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2021 British Association of Dermatologists.
Références
Cochrane Database Syst Rev. 2020 Jan 20;1:CD011628
pubmed: 31958161
Ann Intern Med. 2010 Jul 6;153(1):66-7
pubmed: 20621920
J Am Acad Dermatol. 2009 Jun;60(6):1024-31
pubmed: 19467374
Pediatrics. 2013 Oct;132(4):e1043-7
pubmed: 24019411
N Engl J Med. 2019 Mar 7;380(10):981-983
pubmed: 30855749
Trials. 2020 Feb 10;21(1):158
pubmed: 32041649
N Engl J Med. 2009 Jun 4;360(23):2426-37
pubmed: 19494218
J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1792-1799
pubmed: 28585342
JAMA Dermatol. 2018 Mar 1;154(3):309-316
pubmed: 29417135
Br J Dermatol. 2019 May;180(5):1069-1076
pubmed: 30155885
J Dermatolog Treat. 2022 Feb;33(1):73-86
pubmed: 32279586
J Am Acad Dermatol. 2013 Aug;69(2):e79-88
pubmed: 23207011
J Neuroinflammation. 2017 Jan 21;14(1):16
pubmed: 28109186
Arch Dermatol. 2012 Mar;148(3):297-9
pubmed: 22431771
Ann Rheum Dis. 2012 Jun;71(6):1098-100
pubmed: 22219141
Br J Dermatol. 2014 Sep;171(3):646-9
pubmed: 24684162
Curr Opin Immunol. 2017 Dec;49:1-8
pubmed: 28738209
Trials. 2018 Aug 29;19(1):465
pubmed: 30157880
Ann Dermatol Venereol. 2017 Mar;144(3):169-175
pubmed: 28242094
Br J Dermatol. 2001 Oct;145(4):546-53
pubmed: 11703279
J Am Acad Dermatol. 2019 May;80(5):1344-1352
pubmed: 30716404
J Allergy Clin Immunol. 2019 Mar;143(3):1021-1026
pubmed: 30036598
Br J Dermatol. 2004 Sep;151(3):594-9
pubmed: 15377345
Br J Dermatol. 2014 Jan;170(1):202-4
pubmed: 23909475
Br J Dermatol. 2007 Feb;156(2):258-62
pubmed: 17223864
Dermatol Ther (Heidelb). 2021 Apr;11(2):571-585
pubmed: 33661508
Stat Med. 2020 Sep 20;39(21):2815-2842
pubmed: 32419182
Br J Dermatol. 2020 Apr;182(4):889-899
pubmed: 31286480