Journal of Investigative Dermatology ( IF 6.5 ) Pub Date : 2020-02-21 , DOI: 10.1016/j.jid.2020.01.025 Joel M Gelfand 1 , Daniel B Shin 1 , Kristina Callis Duffin 2 , April W Armstrong 3 , Andrew Blauvelt 4 , Stephen K Tyring 5 , Alan Menter 6 , Scott Gottlieb 7 , Benjamin N Lockshin 8 , Eric L Simpson 9 , Farid Kianifard 10 , Rajendra Prasad Sarkar 11 , Elisa Muscianisi 10 , Jennifer Steadman 10 , Mark A Ahlman 12 , Martin P Playford 13 , Aditya A Joshi 13 , Amit K Dey 13 , Thomas J Werner 1 , Abass Alavi 1 , Nehal N Mehta 13
Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose–positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was –0.053 (95% confidence interval = –0.169 to 0.064; P = 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P = 0.0063) and ferritin (P = 0.0354), and an increase in fetuin-A (P = 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
中文翻译:
苏金单抗治疗中重度斑块状银屑病 (VIP-S) 主动脉血管炎症的随机安慰剂对照试验。
银屑病是一种慢性免疫介导的疾病,与心血管事件和死亡率的风险增加有关。苏金单抗选择性地中和 IL-17A,并已报告在各种银屑病疾病表现中具有高疗效和良好的安全性。在为期 12 周的随机、安慰剂对照、双盲治疗期之后,中度至重度银屑病患者接受了 40 周苏金单抗治疗。在第 0、12 和 52 周使用18 F-2 -氟脱氧葡萄糖 - 正电子发射断层扫描/计算机断层扫描成像和基于血液的心脏代谢评估血管炎症。 苏金单抗从基线到第 12 周的主动脉炎症变化差异(n = 46) 与安慰剂 (n =45) 为 –0.053(95% 置信区间 = –0.169 至 0.064;P = 0.37)。与安慰剂相比,苏金单抗治疗观察到总胆固醇、低密度脂蛋白和低密度脂蛋白颗粒略有增加,但炎症、肥胖、胰岛素抵抗或糖尿病的预测指标没有变化。在第 52 周,TNF-α ( P = 0.0063) 和铁蛋白 ( P = 0.0354) 减少,胎球蛋白-A 增加 ( P =0.0024),与基线相比,苏金单抗治疗观察到。与基线相比,苏金单抗治疗未观察到主动脉炎症或晚期脂蛋白表征、肥胖或胰岛素抵抗的显着变化。治疗 52 周后,苏金单抗对主动脉血管炎症和心脏代谢疾病的生物标志物表现出中性影响。