Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response.
Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response.
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DOI：
10.1053/j.gastro.2016.08.004
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发表时间：
2016-12
期刊：
影响因子：
29.4
通讯作者：
HCV-TARGET Study Group
中科院分区：
文献类型：
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作者：
Terrault NA;Zeuzem S;Di Bisceglie AM;Lim JK;Pockros PJ;Frazier LM;Kuo A;Lok AS;Shiffman ML;Ben Ari Z;Akushevich L;Vainorius M;Sulkowski MS;Fried MW;Nelson DR;HCV-TARGET Study Group
雷迪帕韦和索磷布韦的组合已被批准用于治疗基因 1 型丙型肝炎病毒 (HCV) 感染，包括针对未接受过治疗的无肝硬化且 HCV RNA 基线水平<600 万 IU/mL 的患者的 8 周治疗方案。我们分析了一项多中心、前瞻性、观察性研究的数据，以确定使用含有雷迪帕韦和索磷布韦的方案治疗 12 周 (SVR12) 后真实世界的持续病毒学应答，并确定与治疗失败相关的因素。我们收集了 HCV-TARGET 研究的 2099 名参与者的数据，其中包含完整的病毒学数据（符合方案人群）。我们分析了 1788 名接受雷迪帕韦-索磷布韦治疗的患者（282 名患者接受 8 周，910 名患者接受 12 周，510 名患者接受 24 周，86 名患者接受不同持续时间）和 311 名接受雷迪帕韦-索磷布韦加利巴韦林治疗的患者（212 名患者接受 12 周，81 名患者接受 24 周，18 名患者接受其他持续时间）的数据来估计 SVR12（ 95% 置信区间 [CI]）和逻辑回归方法来识别预测 SVR12 的因素。总体研究人群中 25% 是黑人，66% 患有 HCV 基因型 1A 感染，41% 患有肝硬化，50% 有治疗经验，30% 在治疗开始时接受质子泵抑制剂。在符合方案人群中，接受雷迪帕韦-索磷布韦治疗 8 周的患者中有 96% 实现了 SVR12（95% CI，93%–98%），接受药物治疗 12 周的患者中有 97% 实现了 SVR12（95% CI，96%–98%），接受药物治疗 24 周的患者中有 95% 的患者实现了 SVR12（95% CI，93%–97%）。在同时接受利巴韦林治疗的患者中，97% 接受药物治疗 12 周的患者（95% CI，94%–99%）和 95% 接受药物治疗 24 周的患者（95% CI，88%–99%）实现了 SVR12。在 586 名符合 8 周治疗资格的患者中，只有 255 名（44%）接受了 8 周的药物治疗。符合资格并接受 8 周治疗的患者的 SVR12 率与符合 8 周治疗但接受 12 周治疗的患者相似（96%；95% CI，92%–99% vs 98%；95% CI，95%–99%）。预测 SVR12 的因素包括较高的白蛋白（≤3.5 g/dL）、较低的总胆红素（≥1.2 g/dL）、无肝硬化以及未使用质子泵抑制剂。含有雷迪帕韦和索磷布韦的治疗方案对于在不同临床实践环境中接受治疗的多种 HCV 基因型 1 感染患者非常有效。这些现实世界的结果支持了对符合条件的患者扩大使用 8 周治疗方案。改变质子泵抑制剂的使用可能会提高 SVR 率。 ClinicalTrials.gov 编号NCT01474811。
The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%–98%), 97% receiving the drugs for 12 weeks (95% CI, 96%–98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%–97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%–99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%–99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%–99% vs 98%; 95% CI, 95%–99%). Factors that predicted SVR12 were higher albumin (≤3.5 g/dL), lower total bilirubin (≥1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.