格卡瑞韦和哌仑他韦治疗丙型肝炎病毒合并严重肾功能损害患者。
Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment.
机构信息
From the Liver Unit, Auckland City Hospital, Auckland, New Zealand (E.G.); the Texas Liver Institute, University of Texas Health, San Antonio (E.L.); AbbVie, North Chicago, IL (D.P., C.C., Y.L., M.K., F.J.M.); the Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens (G.P.); the James J. Peters Veterans Affairs Medical Center, Bronx, and Icahn School of Medicine at Mount Sinai, New York - both in New York (N.B.); Imperial College Healthcare, London (A.B.); Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris (S.P.), and Centre Hospitalier Universitaire de Grenoble, Grenoble (V.L.) - both in France; the Internal Medicine and Hepatology Unit, University of Salerno, Salerno (M.P.), Humanitas Clinical and Research Center, Rozzano (M.C.), and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Università di Milano, Milan (M.C.) - all in Italy; Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Brussels (C.M.); University of British Columbia, Vancouver, Canada (E.M.Y.); and the Department of Medicine, University of Florida, Gainesville (D.R.N.).
出版信息
N Engl J Med. 2017 Oct 12;377(15):1448-1455. doi: 10.1056/NEJMoa1704053.
BACKGROUND
Chronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options.
METHODS
We conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment.
RESULTS
Among the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response.
CONCLUSIONS
Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number, NCT02651194 .).
背景
与没有感染 HCV 的慢性肾脏病患者相比，慢性丙型肝炎病毒（HCV）感染在患有慢性肾脏病的患者中更为常见。患有 HCV 感染的慢性肾脏病患者进展为终末期肾病的风险高于没有 HCV 感染的慢性肾脏病患者。同时患有 HCV 感染和晚期慢性肾脏病的患者的治疗选择有限。
方法
我们进行了一项多中心、开放性、3 期临床试验，以评估 NS3/4A 蛋白酶抑制剂 glecaprevir 和 NS5A 抑制剂 pibrentasvir 联合治疗 12 周在 HCV 基因型 1、2、3、4、5 或 6 感染且伴有代偿性肝脏疾病（伴有或不伴有肝硬化）的成年人中的疗效和安全性，这些患者有严重的肾功能损害、依赖透析或两者兼有。患者患有 4 期或 5 期慢性肾脏病，以前未接受过 HCV 感染治疗，或以前接受过干扰素或聚乙二醇干扰素、利巴韦林、索非布韦或这些药物的联合治疗。主要终点是治疗结束后 12 周时持续病毒学应答。
结果
在这项试验中，共有 104 名患者入组，其中 52%的患者感染基因型 1，16%的患者感染基因型 2，11%的患者感染基因型 3，19%的患者感染基因型 4，2%的患者感染基因型 5 或 6。持续病毒学应答率为 98%（104 例患者中的 102 例；95%置信区间，95 至 100）。在治疗期间没有患者发生病毒学失败，在治疗结束后也没有患者发生病毒学复发。至少有 10%的患者报告有瘙痒、疲劳和恶心等不良反应。有 24%的患者报告有严重的不良事件。有 4 名患者因不良事件提前终止试验治疗；其中 3 名患者有持续病毒学应答。
结论
glecaprevir 和 pibrentasvir 治疗 12 周可使患有 4 期或 5 期慢性肾脏病和 HCV 感染的患者获得较高的持续病毒学应答率。（由 AbbVie 资助；ClinicalTrials.gov 编号，NCT02651194）。
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