Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial.

Abstract

BACKGROUND:

Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis.

OBJECTIVE:

We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab.

METHODS:

Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n = 248); or adalimumab (80 mg week 0, then 40 mg week 1, and every 2 weeks through week 23; n = 248). At week 28, guselkumab 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 90) responders were rerandomized to guselkumab or placebo with guselkumab after loss of response. Placebo→guselkumab responders and adalimumab responders received placebo, then guselkumab after loss of response. Nonresponders received guselkumab.

RESULTS:

At week 16, more patients receiving guselkumab achieved an Investigator Global Assessment (IGA) score 0/1 (cleared/minimal) (84.1% vs 8.5%) and PASI 90 (70.0% vs 2.4%) versus placebo (coprimary end points). Guselkumab was superior to adalimumab at week 16 (IGA score 0/1, 75% or greater improvement in PASI score from baseline, and PASI 90) and week 24 (IGA score 0/1 and 0, PASI 90, 100% improvement in PASI score from baseline) (P < .001). From weeks 28 to 48, better persistence of response was observed in guselkumab maintenance versus withdrawal groups (P < .001). Of adalimumab nonresponders who switched to guselkumab, 66.1% achieved PASI 90 at week 48. Guselkumab improved patient-reported outcomes. Adverse events were comparable among groups.

LIMITATIONS:

One-year follow-up limits retreatment data.

CONCLUSIONS:

Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders.

• Authors: Kristian Reich, April W Armstrong, Peter Foley, Michael Song, Yasmine Wasfi, Bruce Randazzo, Shu Li, Y-K Shen, Kenneth B Gordon
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 76 Issue 3 Pg. 418-431 (Mar 2017) ISSN: 1097-6787 [Electronic] United States
• PMID: 28057361 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Dermatologic Agents
• Interleukin-23
• Placebos
• guselkumab
• Adalimumab

Topics

• Adalimumab (adverse effects, therapeutic use)
• Adult
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Dermatologic Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Drug Substitution
• Female
• Humans
• Interleukin-23 (antagonists & inhibitors)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Placebos
• Psoriasis (drug therapy)
• Quality of Life
• Retreatment
• Severity of Illness Index
• Withholding Treatment