ARC-520 或 JNJ-3989 有限治疗后的长期乙型肝炎表面抗原反应

IF 23 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Pub Date : 2024-09-12 DOI:10.1136/gutjnl-2024-333026
Lung Yi Mak, Christine I Wooddell, Oliver Lenz, Thomas Schluep, James Hamilton, Heather L Davis, Xianhua Mao, Wai-Kay Seto, Michael Biermer, Man-Fung Yuen
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引用次数: 0

摘要

背景与目的 RNA 干扰已在慢性乙型肝炎(CHB)感染患者中得到广泛应用。我们的目的是鉴定小干扰 RNA(siRNA)对乙型肝炎表面抗原(HBsAg)抑制的长期疗效。方法 我们对在本中心接受 siRNA(ARC-520 或 JNJ-73763989 (JNJ-3989))联合核苷类似物(NUC)治疗的 CHB 患者进行了前瞻性随访。参加者中包括 15 名每月注射 4 次 ARC-520 的患者、38 名每周注射 1 次、2 次或 4 次 JNJ-3989 的患者,以及 5 名在之前的临床试验中注射安慰剂的患者。根据原始方案进行连续血液采样,每 24 周完成一次,直至最后一次随访(LFU),平均持续时间为 52.5 个月。结果 在 53 名接受 NUC+siRNA 治疗的参与者中(平均年龄 46.8 岁,基线 HBsAg 3.08 log,83% 曾接受过 NUC 治疗,34% 乙肝 e 抗原+),达到 HBsAg 血清清除率或在最低点时达到 100 IU/mL,或距最后一次给药时间≤24 周时能维持或达到 HBsAg <100 IU/mL(LFU)的患者比例分别为:在 LFU 时,HBsAg <100 IU/mL;在 LFU 时,HBsAg <100 IU/mL;在 LFU 时,HBsAg <100 IU/mL。与安慰剂受试者相比,siRNA受试者的HBsAg年总体下降速度更快(0.08 vs 0.21 log IU/mL/年),这主要归功于第一年的变化。年龄与 LFU 的 HBsAg 下降呈负相关(r=-0.427,p=0.001)。结论 短期 siRNA 治疗可抑制 HBsAg 表达,对部分参与者的疗效可延长至 6 年。与该研究相关的所有数据均包含在文章中或作为在线补充信息上传。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989
Background and aims RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression. Methods We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months. Results Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or <100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg <100 IU/mL and >100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg <100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=−0.427, p=0.001). Conclusion Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants. All data relevant to the study are included in the article or uploaded as online supplemental information.
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来源期刊
Gut
Gut 医学-胃肠肝病学
CiteScore
45.70
自引率
2.40%
发文量
284
审稿时长
1.5 months
期刊介绍: Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts. As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.
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