法国病毒性肝病研究所Fabien Zoulim团队研究了布尔韦肽联合聚乙二醇干扰素治疗慢性丁型肝炎的疗效与安全性。相关论文发表在2024年6月6日出版的《新英格兰医学杂志》上。

在一项3期临床试验中，布尔韦肽单药治疗导致慢性丁型肝炎患者出现病毒学缓解。指南建议将聚乙二醇干扰素（聚乙二醇干扰素）α-2a作为该疾病的标签外治疗方法。布尔韦肽和聚乙二醇干扰素α-2a联合治疗的作用，特别是在有限治疗方面，尚不清楚。

在这项2b期开放标签试验中，研究组随机分配患者单独接受聚乙二醇干扰素α-2a（每周180μg）治疗48周；每日剂量为2 mg或10 mg的布尔韦肽加聚乙二醇干扰素α-2a（每周180μg），持续48周，随后每日剂量相同的布尔韦肽持续48周；或单独每日剂量为10mg的布尔韦肽96周。所有患者在治疗结束后随访48周。主要终点是治疗结束后24周检测不到的丁型肝炎病毒（HDV）RNA水平。10 mg布尔韦肽加聚乙二醇干扰素α-2a组和10 mg布尔韦肽单药治疗组间进行主要比较。

共有24名患者单独接受聚乙二醇干扰素α-2a治疗，50名接受2 mg和50名接受10 mg布尔韦肽加聚乙二醇干扰素α2a治疗，50名接受10 mg布尔韦肽单药治疗。在治疗结束后24周，聚乙二醇干扰素α-2a组17%的患者、2mg布尔韦肽加聚乙二醇干扰素α2a组32%的患者、10mg布尔韦肽加聚乙二醇干扰素β-2a组46%的患者和10mg布尔韦肽组12%的患者检测不到HDV RNA。

在初步比较中，组间差异为34个百分点（95%置信区间，15至50；P<0.001）。在治疗结束后48周，聚乙二醇干扰素α-2a组25%的患者、2mg布尔韦肽加聚乙二醇干扰素α2a组26%的患者、10mg布尔韦肽加聚乙二醇干扰素β-2a组46%的患者和10mg布尔韦肽组12%的患者检测不到HDV RNA。最常见的不良事件是白细胞减少、中性粒细胞减少和血小板减少。大多数不良事件的严重程度为1级或2级。

研究结果表明，就治疗结束后24周检测不到的HDV RNA水平而言，10 mg布尔韦肽加聚乙二醇干扰素α-2a的组合优于布尔韦肽单药治疗。

附：英文原文

Title: Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D

Author: Tarik Asselah, Vladimir Chulanov, Pietro Lampertico, Heiner Wedemeyer, Adrian Streinu-Cercel, Victor Pantea, Stefan Lazar, Gheorghe Placinta, George S. Gherlan, Pavel Bogomolov, Tatyana Stepanova, Viacheslav Morozov, Vladimir Syutkin, Olga Sagalova, Dmitry Manuilov, Renee-Claude Mercier, Lei Ye, Ben L. Da, Grace Chee, Audrey H. Lau, Anu Osinusi, Marc Bourliere, Vlad Ratziu, Stanislas Pol, Marie-Nolle Hilleret, Fabien Zoulim

Issue&Volume: 2024-06-06

Abstract:

BACKGROUND

In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear.

METHODS

In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 μg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 μg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group.

RESULTS

A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity.

CONCLUSIONS

The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment.

DOI: NJ202406060000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2314134