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

• Published in: JID innovations Vol. 4; no. 5; p. 100287
• Main Authors: Blauvelt, Andrew, Langley, Richard G., Branigan, Patrick J., Liu, Xuejun, Chen, Yanqing, DePrimo, Samuel, Ma, Keying, Scott, Brittney, Campbell, Kim, Muñoz-Elías, Ernesto J., Papp, Kim A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-09-2024; Elsevier
• Subjects: Adalimumab; Biomarkers; Guselkumab; IL-23/IL-17 pathway; Original; Psoriasis; IL-23/IL-17 pathway; Psoriasis; PSTR; DEG; LS; MDC; HLS; PD; FDR; GSVA; Biomarkers; T17; Adalimumab; FC; ADA; NL; Guselkumab
• ISSN: 2667-0267; 2667-0267
• DOI: 10.1016/j.xjidi.2024.100287

Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23–driven IL-17–producing T cell and other IL-23 receptor–positive IL-17–producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1.
Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA.
Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (P < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all P < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway–associated and psoriasis-associated genes.
These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. Trial registration:ClinicalTrials.govClinicalTrials.gov (NCT02207231).