Guselkumab Efficacy after Withdrawal Is Associated with Suppression of Serum IL-23-Regulated IL-17 and IL-22 in Psoriasis: VOYAGE 2 Study

TY - JOUR

T1 - Guselkumab Efficacy after Withdrawal Is Associated with Suppression of Serum IL-23-Regulated IL-17 and IL-22 in Psoriasis: VOYAGE 2 Study

AU - Gordon, Kenneth B

AU - Armstrong, April W

AU - Foley, Peter

AU - Song, Michael

AU - Shen, Yaung-Kaung

AU - Li, Shu

AU - Muñoz-Elías, Ernesto J

AU - Branigan, Patrick

AU - Liu, Xuejun

AU - Reich, Kristian

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019/12

Y1 - 2019/12

N2 - BACKGROUND: Guselkumab selectively inhibits IL-23 and in psoriasis, produces high clinical responses, including durable maintenance after treatment withdrawal in some patients. The relationships between IL-23 blockade, serum markers downstream of IL-23 signaling, and withdrawal were explored with guselkumab in VOYAGE 2.METHODS: At week 28, patients with ≥90% Psoriasis Area and Severity Index improvement from baseline (PASI 90) were rerandomized to withdrawal and received placebo (n = 182), or maintenance therapy (n = 193). The guselkumab withdrawal group reinitiated guselkumab upon loss of ≥50% of week- 28 PASI improvement or by week 72. Cytokine changes associated with psoriasis recurrence (serum IL-17A, IL-17F, IL-22, and IL-23) after withdrawal were evaluated.RESULTS: Efficacy in the guselkumab maintenance group was sustained through week 72, whereas efficacy diminished in the guselkumab withdrawal group (PASI 90, 86.0% vs. 11.5%). After 20 weeks of retreatment, 80.4% of guselkumab withdrawal patients achieved PASI 90 responses versus baseline. Maintenance of response after withdrawal was associated with suppression of IL-17A, IL-17F, and IL-22. Increases in cytokine levels had poor predictive power for psoriasis reoccurrence as these increases lagged behind increases in PASI scores.CONCLUSION: Upon guselkumab withdrawal, most patients lost clinical response and regained responses with retreatment. Correlation of IL-23 signaling serum cytokines increased with disease recurrence, supporting the role of IL-23 in expansion and maintenance of CD4+ T helper type 17, T helper type 22, and related CD8+ T-cell subsets producing IL-17A, IL-17F, and IL-22.

AB - BACKGROUND: Guselkumab selectively inhibits IL-23 and in psoriasis, produces high clinical responses, including durable maintenance after treatment withdrawal in some patients. The relationships between IL-23 blockade, serum markers downstream of IL-23 signaling, and withdrawal were explored with guselkumab in VOYAGE 2.METHODS: At week 28, patients with ≥90% Psoriasis Area and Severity Index improvement from baseline (PASI 90) were rerandomized to withdrawal and received placebo (n = 182), or maintenance therapy (n = 193). The guselkumab withdrawal group reinitiated guselkumab upon loss of ≥50% of week- 28 PASI improvement or by week 72. Cytokine changes associated with psoriasis recurrence (serum IL-17A, IL-17F, IL-22, and IL-23) after withdrawal were evaluated.RESULTS: Efficacy in the guselkumab maintenance group was sustained through week 72, whereas efficacy diminished in the guselkumab withdrawal group (PASI 90, 86.0% vs. 11.5%). After 20 weeks of retreatment, 80.4% of guselkumab withdrawal patients achieved PASI 90 responses versus baseline. Maintenance of response after withdrawal was associated with suppression of IL-17A, IL-17F, and IL-22. Increases in cytokine levels had poor predictive power for psoriasis reoccurrence as these increases lagged behind increases in PASI scores.CONCLUSION: Upon guselkumab withdrawal, most patients lost clinical response and regained responses with retreatment. Correlation of IL-23 signaling serum cytokines increased with disease recurrence, supporting the role of IL-23 in expansion and maintenance of CD4+ T helper type 17, T helper type 22, and related CD8+ T-cell subsets producing IL-17A, IL-17F, and IL-22.

U2 - 10.1016/j.jid.2019.05.016

DO - 10.1016/j.jid.2019.05.016

M3 - SCORING: Journal article

C2 - 31207232

VL - 139

SP - 2437-2446.e1

JO - J INVEST DERMATOL

JF - J INVEST DERMATOL

SN - 0022-202X

IS - 12

ER -