通用型索磷布韦联合达卡他韦以及索磷布韦/维帕他韦治疗丙型肝炎病毒3型感染患者的疗效与安全性:来自巴基斯坦的真实世界结果

Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan.

作者信息

Mushtaq Saima, Akhter Tayyab Saeed, Khan Amjad, Sohail Aamir, Khan Arshad, Manzoor Sobia

机构信息

Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical College and Allied Hospitals, Rawalpindi, Pakistan.

出版信息

Front Pharmacol. 2020 Sep 2;11:550205. doi: 10.3389/fphar.2020.550205. eCollection 2020.

Abstract

BACKGROUND

Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3.

METHODS

Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan.

RESULTS

Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 3.8%, = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35-8.46,  = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49-109.6, = <0.001). Skin rash (51 44%) and oral ulcers (45 40%) were high in patients receiving SOF-DCV then SOF-VEL.

CONCLUSIONS

Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.

摘要

背景

直接抗病毒药物(DAA)治疗方案对慢性丙型肝炎病毒(HCV)感染非常有效。然而,基因3型(GT3)HCV患者的反应欠佳。本研究旨在确定哪种基于DAA的治疗方案是GT3患者的最佳选择。

方法

多家政府和私立三级医疗机构参与了这项针对接受DAA治疗的HCV-GT3患者的真实研究。在巴基斯坦国家丙型肝炎项目中评估了仿制索磷布韦+达卡他韦±利巴韦林(SOF+DCV±RBV)和索磷布韦/维帕他韦±利巴韦林(SOF/VEL±RBV)的疗效和安全性。

结果

在1388名参与者中,70%的患者在政府三级医疗机构接受SOF+DCV治疗,30%的患者在私立三级医疗机构接受SOF/VEL治疗。总体持续病毒学应答(SVR)率为95.5%。慢性HCV患者中,SOF+DCV(94.4%)和SOF/VEL(94.7%)在12周时的SVR率相当。然而,在接受SOF/VEL+RBV治疗的肝硬化患者中,24周时的SVR率高于接受SOF+DCV+RBV治疗的患者(88%对83%)。SOF-DCV方案的无应答者高于SOF-VEL方案(4.1%对3.8%,P=0.05)。在多变量模型中,非SVR的显著预测因素是年龄>60岁(比值比[OR]4.46;95%CI,2.35-8.46,P<0.001)和肝硬化(OR 53.91;95%CI,26.49-109.6,P<0.001)。接受SOF-DCV治疗的患者出现皮疹(51%对44%)和口腔溃疡(45%对40%)的比例高于接受SOF-VEL治疗的患者。

结论

总体而言,仿制SOF+DCV±RBV和SOF/VEL±RBV的SVR12率同样高。然而,SOF/VEL+RBV在肝硬化患者中的SVR率高于SOF+DCV+RBV。无论采用何种治疗方案,高龄和肝硬化都是SVR几率降低的显著预测因素。此外,这些治疗方案在慢性HCV患者中耐受性良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4be/7493013/c8ec89488201/fphar-11-550205-g001.jpg

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