Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study.

Autor: Krueger J; Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York, USA., Langley RG; Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada., Nigen S; Sima Recherche, Université de Montréal, Montreal, Quebec, Canada., Kasparek T; Novartis Pharma AG, Basel, Switzerland., Di Comite G; Novartis Pharma K.K., Tokyo, Japan., Ortmann CE; Novartis Pharma AG, Basel, Switzerland., Garcet S; Laboratory of Investigative Dermatology, The Rockefeller University, New York, New York, USA., Kolbinger F; Novartis Institutes for BioMedical Research, Basel, Switzerland., Reich K; Translational Research in Inflammatory Skin Disease, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk: angličtina
Zdroj: Experimental dermatology [Exp Dermatol] 2023 Oct; Vol. 32 (10), pp. 1834-1847. Date of Electronic Publication: 2023 Jun 05.
DOI: 10.1111/exd.14828
Abstrakt: 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.
(© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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