Kenneth B Gordon1, April W Armstrong2, Peter Foley3, Michael Song4, Yaung-Kaung Shen4, Shu Li4, Ernesto J Muñoz-Elías4, Patrick Branigan4, Xuejun Liu4, Kristian Reich5. 1. Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 2. University of Southern California, Los Angeles, California, USA. 3. The University of Melbourne, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Probity Medical Research Inc., Skin & Cancer Foundation Inc., Carlton, Victoria, Australia. 4. Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. 5. Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Skinflammation Center, Hamburg, Germany; Dermatologikum Berlin, Berlin, Germany. Electronic address: k.reich@uke.de.
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.
RCT Entities:
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: K B Gordon; M Lebwohl; K A Papp; H Bachelez; J J Wu; R G Langley; A Blauvelt; B Kaplan; M Shah; Y Zhao; R Sinvhal; K Reich Journal: Br J Dermatol Date: 2021-11-24 Impact factor: 11.113
Authors: Marie Masson Regnault; Jason Shourick; Fatma Jendoubi; Marie Tauber; Carle Paul Journal: Am J Clin Dermatol Date: 2022-04-30 Impact factor: 6.233
Authors: Andrew Blauvelt; Craig L Leonardi; Melinda Gooderham; Kim A Papp; Sandra Philipp; Jashin J Wu; Atsuyuki Igarashi; Mary Flack; Ziqian Geng; Tianshuang Wu; Anne Camez; David Williams; Richard G Langley Journal: JAMA Dermatol Date: 2020-06-01 Impact factor: 10.282