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
Oregon Medical Research Center, Portland, Oregon, USA.
Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
JID Innov. 2024 Jun 5;4(5):100287. doi: 10.1016/j.xjidi.2024.100287. eCollection 2024 Sep.
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 ( < .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 < .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. ClinicalTrials.govClinicalTrials.gov (NCT02207231).
银屑病是一种免疫介导的炎症性疾病，其特征在于白细胞介素-23（IL-23）驱动的产生白细胞介素-17（IL-17）的T细胞以及其他表达IL-23受体的产生IL-17的细胞反应被激活。在治疗中度至重度银屑病方面，用古塞库单抗选择性阻断IL-23p19优于用阿达木单抗（ADA）阻断肿瘤坏死因子-α（TNF-α）。目的：在VOYAGE 1研究中比较了古塞库单抗与ADA对银屑病患者的药效学反应。
在基线以及治疗后4、24和48周，对患者亚组进行炎症细胞因子血清水平评估（n = 118），并收集皮损和非皮损皮肤活检样本（n = 38），以评估古塞库单抗与ADA的药效学反应。
与基线相比，至第4周时，古塞库单抗使血清IL-17A、IL-17F和IL-22水平迅速降低，这些降低在第24周和第48周时仍持续存在（P <.001）。与ADA相比，古塞库单抗在第48周时使IL-17A和IL-22降低的幅度更大，在第4、24和48周时使IL-17F降低的幅度更大（均P <.05）。在皮肤中，古塞库单抗降低了IL-23/IL-17途径相关基因和银屑病相关基因的表达。
这些数据详细描述了使用美国食品药品监督管理局（FDA）批准剂量的古塞库单抗和ADA，随着时间推移在人体血液和组织中对IL-23p19和TNF-α抑制的药效学抗炎反应。ClinicalTrials.gov注册号：ClinicalTrials.gov（NCT02207231）。
