Background & Aims

The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis.

Methods

We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.

Results

Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively.

Conclusions

In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.

中文翻译：

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在对未接受过治疗的丙型肝炎病毒感染患者的综合分析中，八周的 Glecaprevir/Pibrentasvir 治疗是安全有效的。

背景与目标

直接作用的抗病毒组合 glecaprevir/pibrentasvir 已获得美国食品和药物管理局的批准，可用于治疗未接受过治疗且无肝硬化或代偿期肝硬化的丙型肝炎病毒 (HCV) 感染患者 8 周。我们对试验数据进行了综合分析，以评估 8 周 glecaprevir/pibrentasvir 在未接受过治疗的无肝硬化或代偿期肝硬化患者中的总体疗效和安全性。

方法

我们汇集了来自 8 项 2 期或 3 期试验的数据，这些患者接受了 8 周 glecaprevir/pibrentasvir 治疗的 HCV 基因型 1 至 6 感染、无肝硬化或代偿期肝硬化的初治患者。

结果

在 1248 名患者中，343 名（27%）患有肝硬化。大多数患者是白人（80%），有 HCV 基因 1 型感染（47%）或基因 3 型感染（22%）；中位年龄为54岁。治疗后第 12 周持续病毒学应答的总体比率在意向治疗 (ITT) 中为 97.6% (1218 of 1248)，在改良 ITT 人群中为 99.3% (1218 of 1226)。当我们排除代偿期肝硬化的基因型 3 感染患者（与欧洲标签一致）时，治疗后第 12 周的持续病毒学应答率在 ITT 中为 97.6%，在改良 ITT 人群中为 99.4%。在 ITT 人群中发生了 8 例病毒学失败（7 例发生在无肝硬化患者中，1 例发生在肝硬化患者中）。病毒学失败与晚期肝病的标志物或感兴趣的人群（当前饮酒、阿片类药物替代疗法、注射吸毒史和严重肾功能损害）。58% 的患者发生治疗中出现的不良事件 (AE)。最常见的 AE (>10%) 是头痛 (12%) 和疲劳 (12%)。导致 glecaprevir/pibrentasvir 停药的严重 AE 和 AE 分别在 2% 和不到 1% 的患者中报告。

结论

在对 8 项试验数据的汇总分析中，我们发现 8 周的 glecaprevir/pibrentasvir 治疗对患有或不患有肝硬化的 HCV 基因型 1 至 6 感染的初治患者有效且耐受性良好。