Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C
Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C
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DOI：
10.14218/jcth.2019.00018
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发表时间：
2019-07
影响因子：
3.6
通讯作者：
Lai Wei;J. Shang;Yuanji Ma;Xiaoyuan Xu;Yan Huang;Y. Guan;Z. Duan;Wenhong Zhang;Zhiliang Gao;Ming-xiang Zhang;Jun Li;J. Jia;Yongfeng Yang;Xiaofeng Wen;Mao-rong Wang;Z. Jia;B. Ning;Yongping Chen;Y. Qi;Jie Du;Jianning Jiang;Lixin Tong;Yao Xie;Jinzi J. Wu
中科院分区：
文献类型：
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作者：
Lai Wei;J. Shang;Yuanji Ma;Xiaoyuan Xu;Yan Huang;Y. Guan;Z. Duan;Wenhong Zhang;Zhiliang Gao;Ming-xiang Zhang;Jun Li;J. Jia;Yongfeng Yang;Xiaofeng Wen;Mao-rong Wang;Z. Jia;B. Ning;Yongping Chen;Y. Qi;Jie Du;Jianning Jiang;Lixin Tong;Yao Xie;Jinzi J. Wu
摘要背景和目的：基因型（GT）1仍然是中国丙型肝炎病毒（HCV）GT的主要类型。超过80%的中国患者携带干扰素敏感的CC等位基因IFNL 4 rs 12979860，这有利于基于干扰素的治疗方案。这项III期临床试验旨在评估利托那韦加强的丹诺匹韦联合聚乙二醇干扰素α-2a和利巴韦林方案治疗12周的中国大陆未经治疗的HCV GT 1感染无肝硬化患者的疗效和安全性。研究方法：这项单组、多中心、III期MANASA研究（NCT 03020082）入组了141例未经治疗的非丙型肝炎病毒GT 1中国患者（年龄≥18岁）。患者接受利托那韦增强的丹诺匹韦（100 mg/100 mg）每日两次联合皮下注射每周一次的聚乙二醇干扰素α-2a（180 μg）和口服利巴韦林（1000/1200 mg/天体重<75/≥75 kg），持续12周。主要终点是治疗结束后12周的持续病毒学应答率。次要终点是安全性结局、耐受性、随时间推移的病毒学应答和复发率。结果：141例患者均为HCV GT 1感染者，其中GT 1b亚型占97.9%（123/141）。单核苷酸多态性检测结果显示，IFNL 4 rs 12979860 CC基因型占87.2%（123/141）。总体而言，140例患者完成了12周治疗，97.1%（136/140）的患者在12周时达到了持续病毒学应答（符合方案人群组，95%置信区间：92.9-99.2%）。仅发生药物相关严重不良事件。大多数不良事件为1级和2级丙氨酸氨基转移酶升高或肝功能障碍。一名患者因车祸中头部严重受伤而停止治疗。结论：利托那韦加强的丹诺匹韦加聚乙二醇干扰素α-2a和利巴韦林三联方案在非丙型肝炎病毒GT 1感染的中国患者中治疗12周后产生了97.1%的持续病毒学应答率，并且安全且耐受性良好。试用注册Clinical-Trials.gov标识符：NCT 03020082
Abstract Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9–99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082