Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
Center for Outcomes Research Liver Diseases, Washington, District of Columbia.
Clin Gastroenterol Hepatol. 2018 Apr;16(4):567-574.e6. doi: 10.1016/j.cgh.2017.11.023. Epub 2017 Nov 16.
BACKGROUND & AIMS: Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12).
We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period.
There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05).
In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.
慢性丙型肝炎病毒（HCV）感染有许多肝内和肝外表现，可以通过患者报告的结局（PRO）来衡量。我们测量了使用最近开发的泛基因型方案治疗 HCV 期间以及治疗结束后 12 周时持续病毒学应答（SVR12）时 PRO 的变化。
我们从两项多中心、双盲、国际 3 期索非布韦、维帕他韦和 voxilaprevir 试验中收集了 PRO 数据，这些试验纳入了以前接受过直接作用抗病毒药物治疗的慢性 HCV 感染患者（任何基因型，59% HCV 基因型 1，43%代偿性肝硬化）（POLARIS-1 和 POLARIS-4）。445 例患者接受了索非布韦、维帕他韦和 voxilaprevir 的联合治疗，151 例患者接受了索非布韦和维帕他韦联合治疗，152 例患者接受了安慰剂治疗。患者在基线、治疗期间和随访期间完成了 SF-36、FACIT-F、CLDQ-HCV 和 WPAI:SHP 问卷。
各组基线临床或人口统计学特征或 PRO 评分无差异（均 P >.05）。接受索非布韦、维帕他韦和 voxilaprevir 联合治疗的组胃肠道症状发生率高于接受索非布韦和维帕他韦或安慰剂的组（P =.0001）。接受索非布韦和维帕他韦治疗的患者中，90.1%达到 SVR12，而接受索非布韦、维帕他韦和 voxilaprevir 治疗的患者中，96.9%达到 SVR12（P =.0008）。治疗 12 周后，两组的某些 PRO 评分均有所改善（0-100 评分增加 2.5 分或 9.1 分；P <.05），但安慰剂组无变化。治疗结束后，所有 PRO 评分的增加均持续或增加（治疗结束后 12 周时增加高达 11.1 分，24 周时增加高达 16.6 分）（除 2 项 PRO 外，所有均 P <.05）。索非布韦和维帕他韦组与索非布韦、维帕他韦和 voxilaprevir 组之间的 PRO 无差异（均 P >.05）。多变量分析显示，在调整临床和人口统计学因素以及基线 PRO 评分后，与安慰剂相比，接受治疗与更高的 PRO 评分相关（高达 5.1 的β）（P <.05）。
在对患有任何基因型慢性 HCV 感染的 2 项 3 期临床试验数据进行分析时，我们发现与安慰剂相比，索非布韦、维帕他韦联合或不联合 voxilaprevir 可提高 PRO 评分。这些发现表明这些方案在治疗期间和 SVR 后具有全面的获益。
