All-Oral Direct-Acting Agent Daclatasvir Plus Asunaprevir for Chronic Genotype 1b Hepatitis C Virus Infection Patients: Real-World Experience of Virologic Response and Side Effects

• Main Authors: Hsuan-Yi Chen, 陳宣怡
• Other Authors: 林俊哲
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/2m99sr

碩士 === 中山醫學大學 === 醫學研究所 === 104 === Introduction: All-oral direct-acting agent dual therapy with Daclatasvir plus Asunaprevir (DCV+ASV) achieved high sustained virological responses (SVR) in genotype 1b (GT-1b) HCV patients in the HALLMARK-DUAL1 study and Phase 3 Japanese study2,3. DCV + ASV is approved in several countries including Taiwan in March, 2016, Japan, Korea, and Latin America, Eastern Europe. In this study, real-world experience of DCV+ASV dual therapy in HCV GT-1b patients was reported. Purpose: To evaluate the efficacy and safety of DCV+ASV therapy in GT-1b HCV infected Taiwanese patients in real-world. Method: Fifty GT-1b HCV infection patients received dual therapy were enrolled at two hospitals in central Taiwan. Five patients (10%) were excluded due to existence of baseline resistance-associated variants (RAVs). Outcomes from 27 patients, who had received 24 weeks dual therapy and been followed up for 24 weeks after end of treatment, were recorded and analyzed. Sustained virologic response at post-treatment week 12 and week 24(SVR12/SVR24) and safety profiles were evaluated. The results were compared with those from HALLMARK-DUAL study. Result: In the real-world group, the mean age was 57 years old ( male/female: 5/ 4); 63% (17/27) patients had advanced liver fibrosis or compensated cirrhosis; 56% patients were treatment-experienced. Virologic response(defined as HCV RNA < LLOQ )at week 4 was 89% (24/27) in the real-world group and74% (477/643) in phase 3 clinical trial group. SVR12 rate was higher than the phase 3 clinical trial group (93 % vs. 84%). SVR12 rates were100% (12/12), 89% (8/9) and 83% (5/6)in treatment-naive, ineligible/intolerant and non-responder patients, respectively. Patients with advanced liver disease or cirrhosis, experience of previous treatment, and higher baseline viral load (HCV RNA ≥ 800,000 IU/mL) had lower SVR 12. The results were similar to those from phase 3 study. Common adverse events included dizziness ( 3/27), pyrexia ( 1/27) and fatigue ( 1/27).There were neither SAE nor AE leading to treatment discontinuation occurred. Conclusion: Daclatasvir plus Asunaprevir were well-tolerated and resulted in a higher SVR rate in the Taiwanese real-world GT-1b HCV patients without baseline NS5A RAVs.