Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

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• 作者：Jan Sperl¹ ; ^{jase@medicon.cz" class="auth_mail" title="E-mail the corresponding author} ; Gabor Horvath² ; Waldemar Halota³ ; Juan Arenas Ruiz-Tapiador⁴ ; Anca Streinu-Cercel⁵ ; Ligita Jancoriene⁶ ; Klara Werling⁷ ; Hege Kileng⁸ ; Seyfettin Koklu⁹ ; Jan Gerstoft¹⁰ ; Petr Urbanek¹¹ ; Robert Flisiak¹² ; Rafael Leiva¹³ ; Edita Kazenaite¹⁴ ; Renate Prinzing¹⁵ ; Sushma Patel¹⁵ ; Jingjun Qiu¹⁵ ; Ernest Asante-Appiah¹⁵ ; Janice Wahl¹⁵ ; Bach-Yen Nguyen¹⁵ ; Eliav Barr¹⁵ ; Heather L. Platt¹⁵
• 关键词：Hepatitis ; Randomized ; Therapy
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：65
• 期：6
• 页码：1112-1119
• 全文大小：772 K

文摘

Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection.

Methods

This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000 IU/ml were randomized to receive 12 weeks of EBR/GZR 50 mg/100 mg once daily (n = 129) or sofosbuvir (400 mg once daily) plus PR (n = 128). Primary efficacy objective was sustained virologic response 12 weeks after the end of therapy (SVR12, HCV RNA <15 IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event.

Results

The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6–15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than −10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, −35.5% to −19.6%; p <0.001]).

Conclusions

EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR.

Lay summary

The combination of elbasvir/grazoprevir for 12 weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12 weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations.

Clinical trial registration

Clinical trials.gov Identifier: NCT02358044.