Krueger, James G, Langley, Richard G, Nigen, Simon, Kasparek, Torben, Di Comite, Gabriele, Ortmann, Christine-Elke, Garcet, Sandra, Kolbinger, Frank and Reich, Kristian (2023) Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study. Experimental dermatology, 32 (10). pp. 1834-1847.

Abstract

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.

Item Type:	Article
Date Deposited:	16 Apr 2024 00:46
Last Modified:	16 Apr 2024 00:46
URI:	https://oak.novartis.com/id/eprint/53154