A clinical trial reports effectiveness of guselkumab in patients with moderate-to-sever plaque psoriasis, easing symptoms to a greater extent than current adalimumab therapy.
Both interleukin-12 and interleukin-23 signaling pathways are increased in psoriatic lesions. These molecules have pro-inflammatory effects related to the symptoms of psoriasis. Therefore antibodies that target these molecules have the potential to reduce the inflammatory symptoms associated with psoriasis.
Guselkumab is a monoclonal antibody that binds to and inhibits signaling of interleukin-23. Based on the results of a previous phase 1 study of guselkumab, a phase 2 study was conducted to test various doses of guselkumab, while also comparing it with another treatment currently used for psoriasis, adalimumab.
The study, reported in the New England Journal of Medicine, included 293 patients with moderate-to-severe- plaque psoriasis, who were either treated with guselkumab (at various doses), placebo, or adalimumab. After 16 weeks of treatment, participants treated with all doses of guselkumab showed significant improvements in disease severity compared with the placebo group. In the highest dose group, 83% of patients had significant improvements, compared with only 7% in the placebo group. Treatment with guselkumab was also superior to treatment with adalimumab; 58% of participants had significant improvement in adalimumab group. The improvements seen in patients treated with guselkumab were maintained for up to 40 weeks.
The trial demonstrates that anti-interleukin-23 therapy with guselkumab is effective at improving the symptoms of moderate-to-severe plaque psoriasis. The improvements are significantly greater than seen when patients are treated with adalimumab.
Worldwide phase 3 trials are currently underway by Janssen Pharmaceuticals to assess the safety and effectiveness of guselkumab for treatment of moderate to severe plaque psoriasis. See below for links to these studies.
Gordon, KB, Duffin, KC, Bissonnette, R, Prinz, JC, Wasfi, Y, Li, S, Shen, Y-K, Szapary, P, Randazzo, B, Reich, K. “A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis” N Engl J Med 2015; 373:136-144. July 9, 2015 DOI: 10.1056/NEJMoa1501646
clinicaltrials.gov “A Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis With Randomized Withdrawal and Retreatment (VOYAGE 2)” Available from: https://www.clinicaltrials.gov/ct2/show/study/NCT02207244?term=guselkumab&recr=Open&no_unk=Y&rank=1&show_locs=Y#locn Last Accessed: July 17, 2015.
clinicaltrials.gov “A Study of Guselkumab in Participants With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab (NAVIGATE)” Available from: https://www.clinicaltrials.gov/ct2/show/NCT02203032?term=guselkumab&recr=Open&no_unk=Y&rank=5 Last Accessed: July 17, 2015.
clinicaltrials.gov “An Efficacy and Safety of CNTO 1959 (Guselkumab) in Participants With Moderate to Severe Plaque-type Psoriasis” Available from: https://www.clinicaltrials.gov/ct2/show/NCT02325219?term=guselkumab&recr=Open&no_unk=Y&rank=6 Last Accessed: July 17, 2015.
Image courtesy of stockimages at FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD