Baseline Clinical, Hormonal and Molecular Markers Associated with Clinical Response to IL-23 Antagonism in Hidradenitis Suppurativa

Background: Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. Clinical trials of IL-23 antagonism have shown high variability leading to abandonment of various clinical trials. IL-23 is known to interact with sex hormones in. monocytes, dendritic cells, and T cells. Relationships of IL-23 clinical response in HS to hormonal and molecular markers of inflammation has not been previously assessed. Objectives: To assess whether baseline clinical, hormonal, or molecular markers are associated with clinical response to IL-23 antagonism with Risankizumab in Hidradenitis Suppurativa. Methods: 26 individuals with Hurley Stage 2/3 disease were administered Risankizumab 150mg Week 0,4,12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Results: Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone, and decreased levels of FSH. nCounter gene expression identified consistent differential expressed genes to previously published RNAseq datasets. Stratification by clinical responders/non responders identified differentially expressed genes included TRAT1, TPSAB1/2, LTA, IL17A, CXCR1 as well as hormonally responsive genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to non-responders. CD11c+ cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Baseline Data, Nanostring nCounter Human Fibrosis V2.0 Panel

背景：化脓性汗腺炎（Hidradenitis Suppurativa, HS）是一种复杂的炎症性疾病，目前其治疗应答预测仍颇具挑战。IL-23拮抗疗法的临床试验展现出较高的变异性，导致多项相关临床试验被迫中止。已知IL-23可在单核细胞、树突状细胞及T细胞中与性激素发生相互作用，但此前尚未有研究评估化脓性汗腺炎患者的IL-23临床应答与炎症的激素及分子标志物之间的关联。
研究目标：旨在评估基线临床、激素或分子标志物是否与化脓性汗腺炎患者接受瑞斯金珠单抗（Risankizumab）的IL-23拮抗治疗的临床应答相关。
研究方法：纳入26例Hurley分期2/3期的化脓性汗腺炎患者，于第0、4、12周给予150mg瑞斯金珠单抗治疗。采集患者基线性激素水平及皮肤活检标本。于第16周通过HiSCR评估临床应答情况，并对比应答者与非应答者之间的差异。
研究结果：IL-23拮抗治疗的临床应答与男性性别、血清总睾酮水平升高及卵泡刺激素（FSH）水平降低显著相关。nCounter基因表达分析鉴定出与既往已发表的RNAseq数据集一致的差异表达基因。通过临床应答者与非应答者进行分层分析，鉴定出的差异表达基因包括TRAT1、TPSAB1/2、LTA、IL17A、CXCR1，以及PLPP4、MAPK10等激素应答基因。免疫组化结果显示，相较于非应答者，应答者体内CD11c、IL-17A及IL-17F阳性细胞数量显著升高。CD11c+细胞与血清总睾酮水平呈显著正相关，与血清FSH水平呈显著负相关。本研究的基线数据来自Nanostring nCounter Human Fibrosis V2.0 Panel（纳米String nCounter人类纤维化V2.0检测试剂盒）。