Long-Term Efficacy of Guselkumab for the Treatment of Moderate-to-Severe Psoriasis: Results from the Phase 3 VOYAGE 1 Trial Through Two Years
August 2018 | Volume 17 | Issue 8 | Original Article | 826 | Copyright © August 2018
Christopher E.M. Griffiths MD,a Kim A. Papp MD,b Alexa B. Kimball MD,c Bruce Randazzo MD,d Michael Song MD,d Shu Li PhD,d Yaung-Kaung Shen PhD,d Andrew Blauvelt MDe
aDermatology Centre, Salford Royal Hospital, University of Manchester, Manchester; NIHR Biomedical Research Centre, Manchester, UK bK. Papp Clinical Research and Probity Research Inc., Waterloo, Ontario, Canada cHarvard Medical School, Boston, MA dJanssen Research & Development, LLC, Spring House, PA eOregon Medical Research Center, Portland, OR
Background: Due to the chronic nature of psoriasis, it is important to assess the sustained response of treatments over time.
Objective: To assess the efficacy of continuous treatment with guselkumab (an interleukin-23 blocker) through two years in the phase 3 VOYAGE 1 trial.
Methods: Patients were randomized to placebo, guselkumab, or adalimumab at baseline. Placebo-randomized patients crossed over to guselkumab at week 16 (placebo→guselkumab) and adalimumab-randomized patients crossed over to guselkumab at week 52 (adalimumab→guselkumab); all patients received open-label guselkumab beyond week 52. Efficacy was assessed based on the Psoriasis Area and Severity Index (PASI; proportion of patients achieving ≥75%, 90%, or 100% improvement [PASI 75/90/100]) and the Investigator’s Global Assessment (IGA; proportion achieving nearly clear [IGA 0/1] or completely clear [IGA 0]). As pre-specified, efficacy data were analyzed using non-responder imputation (NRI; patients with missing data counted as non-responders) after applying treatment failure rules (TFR; patients meeting TFR counted as non-responders thereafter) through week 48 and by applying TFR only from week 52 through 100. All endpoints were also analyzed using NRI and As Observed methodology for the guselkumab group through week 100.
Results: The clinical responses were maintained through week 100 based on all three analyses. Based on pre-specified analyses, proportions of patients who achieved PASI 75, PASI 90, PASI 100, IGA 0/1, and IGA 0 were 94.8%, 82.1%, 49.0%, 82.4%, and 53.8%, respectively, at week 100. Results were similar for the placebo→guselkumab and adalimumab→guselkumab groups at week 100. As expected, proportions of patients achieving these endpoints were similar based on As Observed analyses and slightly lower when the more conservative NRI rules were applied.
Conclusions: High levels of efficacy were maintained through two years of continuous treatment among guselkumab-treated patients, and efficacy improved through two years among adalimumab-treated patients who crossed over to guselkumab at one year.J Drugs Dermatol. 2018;17(8):826-832.
Psoriasis is a chronic immune-mediated disease with predominant skin involvement. Multiple randomized studies of biologic agents have demonstrated the need for continual treatment.1-9 Open-label extensions of clinical trials conducted to assess established biologic agents, including anti-tumor necrosis factor (TNF)-α agents and ustekinumab (an interleukin (IL)-12/23 inhibitor), have shown that many patients will maintain efficacy for years with continuous treatment.10-12 A review of these studies, however, has suggested that up to one-third of patients may lose response through up to almost four years of follow-up, with greater loss associated with anti-TNF-α agents compared with ustekinumab.13Higher drug survival rates for ustekinumab compared with TNF-α blockers have also been observed, with discontinuation of both treatments driven mainly by loss of efficacy.14-16 The loss of efficacy may be related to a variety of factors, including immunogenicity, mechanism of action, accessibility of dose escalation, metabolism of drug, or variability in compliance. More limited, but promising, long-term efficacy data beyond one year are available for newer biologics targeting IL-17.17-19 Therefore, it is critical to monitor new therapies for sustained response, including high levels of efficacy, in both long-term extensions of clinical trials and studies reflecting real-world data.