聚乙二醇干扰素α-2a 联合利巴韦林治疗慢性丙型肝炎
Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.
机构信息
From the Digestive Disease Institute, Virginia Mason Medical Center, Seattle (K.V.K.); Henry Ford Health Systems, Detroit (S.C.G.); University of Pennsylvania, Philadelphia (K.R.R.); University of California Davis Medical Center, Sacramento (L.R.), University of California at San Diego Medical Center, San Diego (M.C.), Scripps Clinic, La Jolla (P.J.P.), and Gilead Sciences, Foster City (G.M.S., D.A., E.S., R.H.H., P.S.P., W.T.S., J.G.M.) - all in California; Hofstra North Shore-Long Island Jewish School of Medicine, Manhasset, NY (D.E.B.); Texas Liver Institute and University of Texas Health Science Center, San Antonio (E.L.), and Texas Clinical Research Institute, Arlington (R.G.) - both in Texas; Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News (M.L.S.), Digestive and Liver Disease Specialists, Norfolk (M.R.), and Metropolitan Liver Diseases, Fairfax (V.R.) - all in Virginia; Center for Liver Diseases, School of Medicine, University of Miami, Miami (E.S.); Quality Medical Research, Nashville (R.H.); Saint Louis University, St. Louis (A.M.D.); Duke University Medical Center, Durham (A.J.M.), and University of North Carolina, Chapel Hill (M.W.F.) - both in North Carolina; and Indianapolis Gastroenterology Research Foundation, Indianapolis (D.P.).
出版信息
N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10.
BACKGROUND
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.
METHODS
In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy.
RESULTS
The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events.
CONCLUSIONS
Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.).
背景
接受核苷酸聚合酶抑制剂索磷布韦联合 NS5A 抑制剂雷迪帕韦治疗 12 周的丙型肝炎病毒（HCV）感染患者，观察到持续病毒学应答率较高。本研究检查了该方案 8 周的治疗。
方法
在这项 3 期、开放标签研究中，我们将 647 例未经治疗的无肝硬化的 HCV 基因型 1 感染患者随机分为 3 组，分别接受雷迪帕韦和索磷布韦（雷迪帕韦-索磷布韦）治疗 8 周，雷迪帕韦-索磷布韦联合利巴韦林治疗 8 周，或雷迪帕韦-索磷布韦治疗 12 周。主要终点是治疗结束后 12 周时的持续病毒学应答。
结果
8 周雷迪帕韦-索磷布韦组的持续病毒学应答率为 94%（95%可信区间[CI]，90 至 97），8 周雷迪帕韦-索磷布韦联合利巴韦林组为 93%（95%CI，89 至 96），12 周雷迪帕韦-索磷布韦组为 95%（95%CI，92 至 98）。与 8 周雷迪帕韦-索磷布韦组的持续病毒学应答率相比，12 周组的应答率高 1 个百分点（97.5%CI，-4 至 6），而接受利巴韦林联合 8 周雷迪帕韦-索磷布韦治疗组的应答率低 1 个百分点（95%CI，-6 至 4）；这些结果表明，基于 12 个百分点的非劣效性边界，8 周雷迪帕韦-索磷布韦方案具有非劣效性。与其他两组相比，利巴韦林组更常见不良事件。没有患者因不良事件而停止接受仅 8 周雷迪帕韦-索磷布韦治疗。
结论
对于无肝硬化的 HCV 基因型 1 感染初治患者，雷迪帕韦-索磷布韦治疗 8 周与持续病毒学应答率较高相关。在方案中加入利巴韦林或将治疗时间延长至 12 周与额外获益无关。（由吉利德科学公司资助；ION-3 ClinicalTrials.gov 编号，NCT01851330）。
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