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

Abstract

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.

• Authors: Kenneth B Gordon, April W Armstrong, Peter Foley, Michael Song, Yaung-Kaung Shen, Shu Li, Ernesto J Muñoz-Elías, Patrick Branigan, Xuejun Liu, Kristian Reich
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 139 Issue 12 Pg. 2437-2446.e1 (12 2019) ISSN: 1523-1747 [Electronic] United States
• PMID: 31207232 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Interleukin-17
• Interleukin-23
• Interleukins
• guselkumab

Topics

• Antibodies, Monoclonal, Humanized (pharmacology)
• Biomarkers (blood)
• Double-Blind Method
• Follow-Up Studies
• Humans
• Interleukin-17 (blood)
• Interleukin-23 (antagonists & inhibitors, blood)
• Interleukins (blood)
• Psoriasis (blood, drug therapy, pathology)
• Recurrence
• Severity of Illness Index
• Treatment Outcome
• Withholding Treatment
• Interleukin-22