Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study
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Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study. / Krueger, James; Langley, Richard G; Nigen, Simon; Kasparek, Torben; Di Comite, Gabriele; Ortmann, Christine-Elke; Garcet, Sandra; Kolbinger, Frank; Reich, Kristian.
In: EXP DERMATOL, Vol. 32, No. 10, 10.2023, p. 1834-1847.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study
AU - Krueger, James
AU - Langley, Richard G
AU - Nigen, Simon
AU - Kasparek, Torben
AU - Di Comite, Gabriele
AU - Ortmann, Christine-Elke
AU - Garcet, Sandra
AU - Kolbinger, Frank
AU - Reich, Kristian
N1 - © 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - Humans
KW - Antibodies, Monoclonal/therapeutic use
KW - Double-Blind Method
KW - Interleukin-17
KW - Interleukin-23
KW - Psoriasis/pathology
KW - Severity of Illness Index
KW - Treatment Outcome
KW - Ustekinumab
U2 - 10.1111/exd.14828
DO - 10.1111/exd.14828
M3 - SCORING: Journal article
C2 - 37272375
VL - 32
SP - 1834
EP - 1847
JO - EXP DERMATOL
JF - EXP DERMATOL
SN - 0906-6705
IS - 10
ER -