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

• Published in: Journal of the American Academy of Dermatology Vol. 76; no. 3; pp. 418 - 431
• Main Authors: Reich, Kristian, Armstrong, April W., Foley, Peter, Song, Michael, Wasfi, Yasmine, Randazzo, Bruce, Li, Shu, Shen, Y.-K., Gordon, Kenneth B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: adalimumab; Adalimumab - adverse effects; Adalimumab - therapeutic use; Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Dermatologic Agents - adverse effects; Dermatologic Agents - therapeutic use; Dermatology; Double-Blind Method; Drug Substitution; efficacy; Female; guselkumab; Humans; interleukin-23; Interleukin-23 - antagonists & inhibitors; Maintenance Chemotherapy; Male; Middle Aged; Placebos; psoriasis; Psoriasis - drug therapy; Quality of Life; Retreatment; safety; Severity of Illness Index; switching; VOYAGE 1; VOYAGE 2; Withholding Treatment; switching; DLQI; PASI 90; IGA; PASI; IL; AE; PASI 75; ISR; NMSC; guselkumab; adalimumab; efficacy; interleukin-23; PASI 100; PSSD; q8w; VOYAGE 2; VOYAGE 1; MACE; psoriasis; safety; SAE; Psoriasis Symptoms and Signs Diary; injection site reaction; Psoriasis Area and Severity Index; 100% improvement in Psoriasis Area and Severity Index score from baseline; Investigator Global Assessment; 75% or greater improvement in Psoriasis Area and Severity Index score from baseline; major adverse cardiovascular event; serious adverse event; interleukin; 90% or greater improvement in Psoriasis Area and Severity Index score from baseline; adverse event; every 8 weeks; Dermatology Life Quality Index; nonmelanoma skin cancer
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2016.11.042

Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis. 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. 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. 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. One-year follow-up limits retreatment data. Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders.