美国北卡罗来纳大学Evan S. Dellon团队研究了抗Siglec-8抗体治疗嗜酸性胃炎和十二指肠炎的疗效。2020年10月22日，《新英格兰医学杂志》发表了该成果。
嗜酸性胃炎和十二指肠炎的特征是胃肠道粘膜嗜酸性粒细胞增多、慢性症状、生活质量受损和缺乏有效治疗方法。肥大细胞激活可能是发病机理之一。AK002（lirentelimab）是一种抗Siglec-8抗体，可消除嗜酸性粒细胞并抑制肥大细胞，在动物模型中显示出可用于治疗嗜酸性胃炎和十二指肠炎的潜力。
在这项临床2期试验中，研究组招募患有症状性嗜酸性胃炎、嗜酸性十二指肠炎或两种疾病都有的成年人，将其随机分配，分别接受低剂量AK002、高剂量AK002或安慰剂治疗，每月输注4次。主要终点是胃肠道嗜酸性粒细胞计数的变化。次要终点是治疗缓解（总症状评分降低30％以上，胃肠道嗜酸性粒细胞计数降低75％以上）和总症状评分的变化。
在接受随机分组的65位患者中，43位被分配接受AK002治疗，22位被分配接受安慰剂治疗。治疗结束后，AK002组的胃肠道嗜酸性粒细胞计数的平均百分比降低了86%，而安慰剂组增加了9％。AK002组中有63％的患者治疗缓解，显著高于安慰剂组（5%）。
AK002组中总症状评分平均降低了48％，安慰剂组降低了22％，差异显著。两组间的不良事件发生率相差不大。但AK002组中有60%的患者发生轻至中度输注相关反应，显著高于安慰剂组（23％）。
总之，对于患有嗜酸性胃炎或十二指肠炎的患者，与安慰剂相比，AK002治疗可显著降低胃肠道嗜酸性粒细胞计数，缓解症状，但输注相关反应更常见。
附：英文原文
Title: Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis
Author: Evan S. Dellon, M.D., M.P.H.,, Kathryn A. Peterson, M.D.,, Joseph A. Murray, M.D.,, Gary W. Falk, M.D.,, Nirmala Gonsalves, M.D.,, Mirna Chehade, M.D., M.P.H.,, Robert M. Genta, M.D.,, John Leung, M.D.,, Paneez Khoury, M.D.,, Amy D. Klion, M.D.,, Sabine Hazan, M.D.,, Michael Vaezi, M.D.,, Adam C. Bledsoe, M.D.,, Sandy R. Durrani, M.D.,, Chao Wang, Ph.D.,, Camilla Shaw, B.S.N., R.N.,, Alan T. Chang, B.S.,, Bhupinder Singh, M.D.,, Amol P. Kamboj, M.D.,, Henrik S. Rasmussen, M.D., Ph.D.,, Marc E. Rothenberg, M.D., Ph.D.,, and Ikuo Hirano, M.D.
Issue&Volume: 2020-10-22
Abstract:
Background
Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti–Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.
Methods
In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.
Results
Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was 86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, 98 percentage points; 95% confidence interval [CI], 121 to 76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was 48% with AK002 and 22% with placebo (least-squares mean difference, 26 percentage points; 95% CI, 44 to 9; P=0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).
Conclusions
In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo.
DOI: 10.1056/NEJMoa2012047
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2012047
The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于美国麻省医学协会，最新IF：176.079
官方网址：http://www.nejm.org/
投稿链接：http://www.nejm.org/page/author-center/home
本期文章：《新英格兰医学杂志》：Vol.383 No.17
