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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2314134

摘要内容如下：

背景

在一项3期临床试验中，Bulevirtide单药治疗在慢性肝炎患者中产生了病毒学应答。聚乙二醇化干扰素（Peginterferon）α-2a被指南推荐为该疾病的标示外治疗。布来韦肽和聚乙二醇干扰素α-2a联合治疗的作用，特别是在有限治疗中的作用尚不清楚。

方法

在这项2B期开放标签试验中，我们将患者随机分配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的布来韦肽联合聚乙二醇干扰素α-2a（每周180μg）治疗48周，随后给予相同每日剂量的布来韦肽治疗48周；或单用布来韦肽每日10mg，共96周。治疗结束后随访48周。主要终点是治疗结束后24周检测不到丁型肝炎病毒（HDV）RNA水平。主要比较10 mg布列韦肽联合聚乙二醇干扰素α-2a治疗组和10 mg布列韦肽单药治疗组。

结果

共有24名患者单独接受聚乙二醇干扰素α-2a治疗，50名患者接受2 mg和50名患者接受10 mg布列韦肽联合聚乙二醇干扰素α-2a治疗，50名患者接受10 mg布列韦肽单药治疗。治疗结束后24周，在聚乙二醇干扰素α-2a组中17%的患者检测不到HDV RNA，在2-mg Bulevirtide+聚乙二醇干扰素α-2a组中32%的患者检测不到HDV RNA，在10-mg Bulevirtide+聚乙二醇干扰素α-2a组中46%的患者检测不到HDV RNA，在10-mg Bulevirtide组中12%的患者检测不到HDV RNA。对于主要比较，组间差异为34个百分点（95%置信区间，15至50；P<0.001）。治疗结束后48周，聚乙二醇干扰素α-2a组中25%的患者检测不到HDV RNA，2-mg布列韦肽+聚乙二醇干扰素α-2a组中26%的患者检测不到HDV RNA，10-mg布列韦肽+聚乙二醇干扰素α-2a组中46%的患者检测不到HDV RNA，10-mg布列韦肽组中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。

结论

在治疗结束后24周，10 mg Bulevirtide联合聚乙二醇干扰素α-2a治疗在检测不到HDV RNA水平方面优于Bulevirtide单药治疗。（由Gilead Sciences资助；MYR 204 ClinicalTrials.gov编号，NCT03852433。）

英文原文如下：

Abstracts

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. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.).

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