VISIBLE: Significant serum cytokine reduction achieved with guselkumab in participants with psoriasis and skin of color

Summary: Levels of disease-driving cytokines are typically elevated in the skin and blood of patients with psoriasis (PsO). VISIBLE, a Phase 3b study, is evaluating efficacy & safety of guselkumab (GUS) in participants (pts) with moderate-to-severe PsO across all skin tones. These post-hoc analyses evaluated the effects of GUS on targeted serum cytokines. VISIBLE pts with plaque (Cohort A) or scalp (Cohort B) PsO were randomized 3:1 to receive GUS 100mg at Week (W) 0, 4, and Q8W or PBO→GUS at W16. Serum cytokine levels (IL-17A, IL-17F, IL-22, BD-2) were measured at baseline (W0) and W4/16/48 in 151 GUS and 50 PBO pts in both cohorts and up to 29 healthy controls (HCs). Serum IL-17F, IL-22, and BD-2 levels were significantly higher at W0 in VISIBLE pts vs HCs. GUS treatment led to significant reductions (log2 fold change from W0 ranging from -0.8 to –5.7) in serum IL-17F, IL-22, and BD-2 through W48 and in PBO→GUS after W16. W0 IL-17F, IL-22, and BD-2 levels significantly correlated (p<0.05) with Psoriasis Area and Severity Index (PASI) and Psoriasis Scalp Severity Index (PSSI) scores. Greater reduction in BD-2 from W0 was associated with W16 PASI90 and PSSI90 response in Cohort A&B pts, respectively. Low PsO BSA (2%−<10%) at W0 in Cohort B was associated with significantly less reduction in IL-17F and BD-2 levels at W16 & W48. No significant differences in serum cytokine changes were noted in subgroups by BMI, sex, or psoriatic arthritis. This serum cytokine study in skin of color PsO pts showed that GUS provided early and sustained serum cytokine reductions through W48. Additional studies may inform our understanding on similarities & differences in pts with PsO from diverse backgrounds. Shawn Kwatra¹, George Han², Jason Hawkes³, Aaron Farberg⁴, B Ungar², T Lee⁵, V Moulton⁵, H Moncrieffe⁵, Monica W. Leung⁶, R Panchakshari⁶, K Rowland⁵, T Alkousakis⁵, O Choi⁵, Jordan Talia², J North⁷ 1. University of Maryland, Baltimore, MD, United States. 2. Icahn School of Medicine at Mt Sinai, NY, NY, United States. 3. Oregon Medical Research Ctr, Portland, OR, United States. 4. Bare Dermatology, Dallas, TX, United States. 5. J&J, Horsham & Spring House, PA, United States. 6. J&J, San Diego, CA, United States. 7. UCSF, San Francisco, CA, United States. Clinical Research: Interventional Research