Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study.
IL-17
guselkumab
resistant psoriatic plaque
secukinumab
ustekinumab
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
11
04
2023
received:
01
02
2023
accepted:
23
04
2023
medline:
23
10
2023
pubmed:
5
6
2023
entrez:
5
6
2023
Statut:
ppublish
Résumé
Interleukin (IL)-23-independent IL-17A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti-IL-12/23-refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL-17A (with secukinumab) versus selective IL-23 inhibition (with guselkumab) in patients with anti-IL-12/23 (ustekinumab)-refractory psoriatic plaques. A 16-week, randomized, open-label, parallel-group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1-10. Patients were randomized 1:1 to receive secukinumab 300 mg (n = 20) or guselkumab 100 mg (n = 20). Biopsies from one refractory ('target plaque') were obtained at baseline and Week 16. The primary endpoint was the proportion of patients whose ustekinumab-refractory target plaque achieved clear/almost clear status (TCS 0-2) at Week 16. Transcriptomic and histological analyses were conducted on target plaques to determine the molecular effects of direct IL-17A versus selective IL-23 inhibition. At Week 16, target plaque clear/almost clear status was achieved in 60.0% of patients treated with secukinumab versus 40.0% of patients treated with guselkumab (p = 0.1715). Molecular analyses identified that secukinumab modulated a greater proportion of psoriasis disease transcriptome genes (72.1% vs. 48.0%) and resulted in more histological responders (72.2% vs. 53.3%) compared with guselkumab. Secukinumab demonstrated a greater clinical and molecular effect on ustekinumab-refractory psoriatic plaques versus guselkumab. These results are consistent with the hypothesis that IL-23-independent IL-17 mechanisms may be relevant to the inflammation driving refractory manifestations of psoriasis.
Substances chimiques
Antibodies, Monoclonal
0
guselkumab
089658A12D
Interleukin-17
0
Interleukin-23
0
secukinumab
DLG4EML025
Ustekinumab
FU77B4U5Z0
Banques de données
ClinicalTrials.gov
['NCT03553823']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1834-1847Informations de copyright
© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.
Références
Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018;55(3):379-390. doi:10.1007/s12016-018-8702-3
Raychaudhuri SK, Saxena A, Raychaudhuri SP. Role of IL-17 in the pathogenesis of psoriatic arthritis and axial spondyloarthritis. Clin Rheumatol. 2015;34(6):1019-1023. doi:10.1007/s10067-015-2961-7
Reich K, Warren RB, Coates LC, Di Comite G. Long term efficacy and safety of secukinumab in the treatment of the multiple manifestations of psoriatic disease. J Eur Acad Dermatol Venereol. 2019;34(6):1161-1173. doi:10.1111/jdv.16124
Griffiths CEM, Barker JNWN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263-271. doi:10.1016/S0140-6736(07)61128-3
Fletcher JM, Moran B, Petrasca A, Smith CM. IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. Clin Exp Immunol. 2020;201(2):121-134. doi:10.1111/cei.13449
Liu T, Li S, Ying S, et al. The IL-23/IL-17 pathway in inflammatory skin diseases: from bench to bedside. Front Immunol. 2020;11:594735. doi:10.3389/fimmu.2020.594735
Cheuk S, Wiken M, Blomqvist L, et al. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014;192(7):3111-3120. doi:10.4049/jimmunol.1302313
Ortega C, Fernandez AS, Carrillo JM, et al. IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol. 2009;86(2):435-443. doi:10.1189/JLB.0109046
Hijnen D, Knol EF, Gent YY, et al. CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-gamma, IL-13, IL-17, and IL-22. J Invest Dermatol. 2013;133(4):973-979. doi:10.1038/jid.2012.456
Papotto PH, Ribot JC, Silva-Santos B. IL-17+ γδ T cells as kick-starters of inflammation. Nat Immunol. 2017;18(6):604-611. doi:10.1038/ni.3726
Pisarska MM, Dunne MR, O'Shea D, Hogan AE. Interleukin-17 producing mucosal associated invariant T cells - emerging players in chronic inflammatory diseases? Eur J Immunol. 2020;50(8):1098-1108. doi:10.1002/eji.202048645
Coquet JM, Chakravarti S, Kyparissoudis K, et al. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci USA. 2008;105(32):11287-11292. doi:10.1073/pnas.0801631105
Bernink JH, Ohne Y, Teunissen MBM, et al. c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies. Nat Immunol. 2019;20(8):992-1003. doi:10.1038/s41590-019-0423-0
Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605-1613. doi:10.4049/jimmunol.1800013
Carrier Y, Ma H-L, Ramon HE, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines In vitro and In vivo: implications in psoriasis pathogenesis. J Invest Dermatol. 2011;131(12):2428-2437. doi:10.1038/jid.2011.234
Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest. 2006;116(5):1218-1222. doi:10.1172/jci28508
Cole S, Murray J, Simpson C, et al. Interleukin (IL)-12 and IL-18 synergize to promote MAIT cell IL-17A and IL-17F production independently of IL-23 signaling. Front Immunol. 2020;11:585134. doi:10.3389/fimmu.2020.585134
Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10(7):479-489. doi:10.1038/nri2800
Ishigame H, Kakuta S, Nagai T, et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009;30(1):108-119. doi:10.1016/j.immuni.2008.11.009
Liu J, Chang HW, Huang ZM, et al. Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8(+) T cells in autoimmunity and cancer. J Allergy Clin Immunol. 2021;147(6):2370-2380. doi:10.1016/j.jaci.2020.11.028
Ehst B, Wang Z, Leitenberger J, et al. Synergistic induction of IL-23 by TNFalpha, IL-17A, and EGF in keratinocytes. Cytokine. 2021;138:155357. doi:10.1016/j.cyto.2020.155357
Appel H, Maier R, Wu P, et al. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther. 2011;13(3):R95. doi:10.1186/ar3370
Bissonnette R, Nigen S, Langley RG, et al. Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial. J Eur Acad Dermatol Venereol. 2014;28(10):1298-1305. doi:10.1111/jdv.12272
Paulissen SM, van Hamburg JP, Davelaar N, Asmawidjaja PS, Hazes JM, Lubberts E. Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23. J Immunol. 2013;191(3):1364-1372. doi:10.4049/jimmunol.1300274
Deodhar A, Gensler LS, Sieper J, et al. Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of Ustekinumab in axial Spondyloarthritis. Arthrit Rheumatol. 2019;71(2):258-270. doi:10.1002/art.40728
Baeten D, Østergaard M, Wei JC-C, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis. 2018;77(9):1295-1302. doi:10.1136/annrheumdis-2018-213328
Jack C, Mashiko S, Arbour N, Bissonnette R, Sarfati M. Persistence of interleukin (IL)-17A+ T lymphocytes and IL-17A expression in treatment-resistant psoriatic plaques despite ustekinumab therapy. Br J Dermatol. 2017;177(1):267-270. doi:10.1111/bjd.15029
Kulig P, Musiol S, Freiberger SN, et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun. 2016;7:13466. doi:10.1038/ncomms13466
Blauvelt A, Papp KA, Griffiths CEM, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405-417. doi:10.1016/j.jaad.2016.11.041
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418-431. doi:10.1016/j.jaad.2016.11.042
Tomalin LE, Russell CB, Garcet S, et al. Short-term transcriptional response to IL-17 receptor-A antagonism in the treatment of psoriasis. J Allergy Clin Immunol. 2020;145(3):922-932. doi:10.1016/j.jaci.2019.10.041
Brodmerkel C, Li K, Garcet S, et al. Modulation of inflammatory gene transcripts in psoriasis vulgaris: differences between ustekinumab and etanercept. J Allergy Clin Immunol. 2019;143(5):1965-1969. doi:10.1016/j.jaci.2019.01.017
Swindell WR, Sarkar MK, Liang Y, et al. RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin. Sci Rep. 2017;7(1):18045. doi:10.1038/s41598-017-18404-9
Mauro D, Macaluso F, Fasano S, Alessandro R, Ciccia F. ILC3 in axial spondyloarthritis: the gut angle. Curr Rheumatol Rep. 2019;21(7):37. doi:10.1007/s11926-019-0834-9
Blauvelt A, Armstrong AW, Langley RG, et al. Efficacy of guselkumab versus secukinumab in subpopulations of patients with moderate-to-severe plaque psoriasis: results from the ECLIPSE study. J Dermatol Treat. 2022;33(4):2317-2324. doi:10.1080/09546634.2021.1959504
Krueger JG, Wharton KA Jr, Schlitt T, et al. IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis. J Allergy Clin Immunol. 2019;144(3):750-763. doi:10.1016/j.jaci.2019.04.029
Lauffer F, Jargosch M, Baghin V, et al. IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema. J Eur Acad Dermatol Venereol. 2020;34(4):800-809. doi:10.1111/jdv.16126
Augustin M, Reich K, Yamauchi P, et al. Secukinumab dosing every two weeks demonstrated superior efficacy compared with dosing every four weeks in patients with psoriasis weighing 90 kg or more: results of a randomised controlled trial. Br J Dermatol. 2022;186(6):942-954. doi:10.1111/bjd.20971