Guselkumab Efficacy after Withdrawal Is Associated with Suppression of Serum IL-23-Regulated IL-17 and IL-22 in Psoriasis: VOYAGE 2 Study
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Guselkumab Efficacy after Withdrawal Is Associated with Suppression of Serum IL-23-Regulated IL-17 and IL-22 in Psoriasis: VOYAGE 2 Study. / Gordon, Kenneth B; Armstrong, April W; Foley, Peter; Song, Michael; Shen, Yaung-Kaung; Li, Shu; Muñoz-Elías, Ernesto J; Branigan, Patrick; Liu, Xuejun; Reich, Kristian.
In: J INVEST DERMATOL, Vol. 139, No. 12, 12.2019, p. 2437-2446.e1.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -