抗Siglec-8抗體治療嗜酸性胃炎和十二指腸炎療效顯著
作者：
小柯機器人發布時間：2020/10/25 22:06:32
美國北卡羅來納大學Evan S. Dellon團隊研究了抗Siglec-8抗體治療嗜酸性胃炎和十二指腸炎的療效。2020年10月22日，《新英格蘭醫學雜誌》發表了該成果。
嗜酸性胃炎和十二指腸炎的特徵是胃腸道黏膜嗜酸性粒細胞增多、慢性症狀、生活質量受損和缺乏有效治療方法。肥大細胞激活可能是發病機理之一。AK002（lirentelimab）是一種抗Siglec-8抗體，可消除嗜酸性粒細胞並抑制肥大細胞，在動物模型中顯示出可用於治療嗜酸性胃炎和十二指腸炎的潛力。
在這項臨床2期試驗中，研究組招募患有症狀性嗜酸性胃炎、嗜酸性十二指腸炎或兩種疾病都有的成年人，將其隨機分配，分別接受低劑量AK002、高劑量AK002或安慰劑治療，每月輸注4次。主要終點是胃腸道嗜酸性粒細胞計數的變化。次要終點是治療緩解（總症狀評分降低30％以上，胃腸道嗜酸性粒細胞計數降低75％以上）和總症狀評分的變化。
在接受隨機分組的65位患者中，43位被分配接受AK002治療，22位被分配接受安慰劑治療。治療結束後，AK002組的胃腸道嗜酸性粒細胞計數的平均百分比降低了86%，而安慰劑組增加了9％。AK002組中有63％的患者治療緩解，顯著高於安慰劑組（5%）。
AK002組中總症狀評分平均降低了48％，安慰劑組降低了22％，差異顯著。兩組間的不良事件發生率相差不大。但AK002組中有60%的患者發生輕至中度輸注相關反應，顯著高於安慰劑組（23％）。
總之，對於患有嗜酸性胃炎或十二指腸炎的患者，與安慰劑相比，AK002治療可顯著降低胃腸道嗜酸性粒細胞計數，緩解症狀，但輸注相關反應更常見。
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