Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy

BackgroundPsoriasis is an immune-mediated inflammatory disease characterized by activation of interleukin (IL)-23–driven IL-17–producing T cell and other IL-23 receptor+ IL-17–producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of tumor necrosis factor-α (TNF-α) with adalimumab in treating moderate-to-severe psoriasis.ObjectivePharmacodynamic (PD) responses of guselkumab versus adalimumab were compared in patients with psoriasis in VOYAGE 1.DesignInflammatory cytokine serum levels were assessed (n=118) and lesional and nonlesional skin biopsies were collected (n=38) in patient subsets at baseline, 4/24/48-weeks post-treatment to evaluate PD responses of guselkumab versus adalimumab.ResultsGuselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by Week 4 versus baseline that were maintained through Weeks 24 and 48 (p<0.001). The magnitude of reduction of IL-17A and IL-22 at Week 48, and IL-17F at Weeks 4/24/48 were greater with guselkumab versus adalimumab (all p<0.05). In skin, guselkumab reduced expression of IL-23/IL-17 pathway-associated and psoriasis-associated genes.ConclusionThese data provide extensive characterization of PD anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with clinically approved doses of guselkumab and adalimumab.