Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.
Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.
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Glecaprevir和Pibrentasvir进行12周的丙型肝炎病毒基因型感染和事先直接作用抗病毒药治疗。
DOI：
10.1002/hep.29081
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Mensa FJ
中科院分区：
文献类型：
--
作者：
Poordad F;Felizarta F;Asatryan A;Sulkowski MS;Reindollar RW;Landis CS;Gordon SC;Flamm SL;Fried MW;Bernstein DE;Lin CW;Liu R;Lovell SS;Ng TI;Kort J;Mensa FJ
尽管针对慢性丙型肝炎病毒（HCV）感染的直接作用抗病毒（DAA）疗法已证明持续病毒学应答率很高，但病毒学失败仍可能发生，可能导致病毒耐药性的出现，从而降低后续治疗的有效性。对于先前含有 DAA 的方案失败的患者，特别是那些使用非结构蛋白 5A 抑制剂的患者，治疗选择是有限的，并且仍然是一个未得到满足的医疗需求领域。这项 2 期开放标签研究 (MAGELLAN-1) 评估了 glecaprevir (GLE) + pibrentasvir (PIB) ± 利巴韦林 (RBV) 对于既往接受含 HCV DAA 治疗病毒学失败的 HCV 基因型 1 感染患者的疗效和安全性。总共 50 名无肝硬化患者被随机分为三组：200 mg GLE + 80 mg PIB（A 组）、300 mg GLE + 120 mg PIB 加 800 mg 每日一次 RBV（B 组）或 300 mg GLE + 120 mg PIB 无 RBV（C 组）。通过意向治疗分析，A、B 和 C 组的患者在治疗后第 12 周达到持续病毒学缓解的比例分别为 100%（6/6，95% 置信区间 61-100）、95%（21/22，95% 置信区间 78-99）和 86%（19/22，95% 置信区间 67-95）。 A 组中没有患者发生病毒学失败，B 组和 C 组各有 1 名患者发生病毒学失败（C 组有 2 名患者失访）。大多数不良事件的严重程度较轻；没有观察到与研究药物相关的严重不良事件，也没有观察到丙氨酸氨基转移酶、总胆红素或血红蛋白的相关实验室异常。结论：GLE 和 PIB 联合治疗基因 1 型 HCV 感染且既往 DAA 治疗失败的患者非常有效且耐受性良好； RBV 联合给药并没有提高疗效。 （肝病学 2017 年；66：389–397）。
Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397).
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影响因子：
29.4
作者：
Gane, Edward;Poordad, Fred;Mensa, Federico J.
通讯作者：
Mensa, Federico J.
DOI：
10.3390/v7122968
发表时间：
2015-12-18
期刊：
Viruses
影响因子：
--
作者：
Ahmed A;Felmlee DJ
通讯作者：
Felmlee DJ
影响因子：
13.5
作者：
Messina, Jane P.;Humphreys, Isla;Flaxman, Abraham;Brown, Anthony;Cooke, Graham S.;Pybus, Oliver G.;Barnes, Eleanor
通讯作者：
Barnes, Eleanor
影响因子：
6.7
作者：
Horner SM;Naggie S
通讯作者：
Naggie S
影响因子：
4.9
作者：
Ng TI;Krishnan P;Pilot-Matias T;Kati W;Schnell G;Beyer J;Reisch T;Lu L;Dekhtyar T;Irvin M;Tripathi R;Maring C;Randolph JT;Wagner R;Collins C
通讯作者：
Collins C