Vunakizumab

The spleen is the principal site of immune hematopoiesis and a major target of Streptococcus agalactiae (S. agalactiae) attack in Nile tilapia (Oreochromis niloticus). However, the immune-regulatory mechanisms employed by this organ against S. agalactiae remain unclear. In this study, integrated transcriptomic analysis of spleen tissue identified 27 genes-among them the core cytokines IL-6, CXCL3 and IL1R2-that responded to S. agalactiae challenge. Genome-wide mining subsequently revealed a total of 27 IL-family members in Nile tilapia. Synteny and chromosomal location analyses indicated that expansion of the family was associated with tandem and whole-genome duplication events. The expression levels of IL-1β, IL-8, CXCL3, and IL-34 were higher than those of other IL-family members in tilapia spleen. Following S. agalactiae infection, IL-6, IL-8, IL-8L, IL-12a, and IL-17D were significantly up-regulated, whereas CXCL3 was markedly down-regulated at 24 h post-infection (hpi). Functional enrichment analysis showed that the 27 genes that respond to S. agalactiae were over-represented in the IL-17 signaling pathway. Co-treatment of primary spleen cells with an IL-17A antagonist attenuated the S. agalactiae-induced up-regulation of IL-6, IL-8, and IL8-like. Bisulfite-sequencing PCR further revealed that putative CpG islands within the IL-17D promoter were demethylated in the spleen following S. agalactiae infection. Collectively, this study provides a theoretical framework for understanding IL-mediated immune regulation in the tilapia spleen during S. agalactiae infection.

Vunakizumab (anti-interleukin-17A antibody) has shown favorable efficacy and safety in treating moderate-to-severe plaque psoriasis. The morbidity and severity of psoriasis vary in different regions of China.

This post-hoc exploratory analysis aims to investigate the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis across different regions of China.

This post-hoc exploratory analysis used data from a phase III trial (NCT04839016), with 461 patients receiving vunakizumab categorized into North (n = 118), Central (n = 252), and South (n = 91) China groups.

Psoriasis area and severity index (PASI)75/90/100 and static physician's global assessment (sPGA) 0/1 response rates were similar among the three groups at week 12 (W12). Additionally, W12-W52 sustained PASI 75/90/100 and sPGA 0/1 response rates were also similar among groups. Similar improvements in patient-reported outcomes, including dermatology life quality index, itch-numerical rating scale, EuroQol-5D, and short form-36, were observed in the three groups. The incidence of adverse events was 80.5%, 90.1%, and 90.1% in the North, Central, and South China groups, respectively.

The efficacy and safety of vunakizumab are not affected by different regions of China in patients with moderate-to-severe plaque psoriasis.