TY - JOUR
T1 - Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin
T2 - A phase III randomized controlled trial
AU - Sperl, Jan
AU - Horvath, Gabor
AU - Halota, Waldemar
AU - Ruiz-Tapiador, Juan Arenas
AU - Streinu-Cercel, Anca
AU - Jancoriene, Ligita
AU - Werling, Klara
AU - Kileng, Hege
AU - Koklu, Seyfettin
AU - Gerstoft, Jan
AU - Urbanek, Petr
AU - Flisiak, Robert
AU - Leiva, Rafael
AU - Kazenaite, Edita
AU - Prinzing, Renate
AU - Patel, Sushma
AU - Qiu, Jingjun
AU - Asante-Appiah, Ernest
AU - Wahl, Janice
AU - Nguyen, Bach-Yen
AU - Barr, Eliav
AU - Platt, Heather L
N1 - Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background & Aims 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.
AB - Background & Aims 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.
KW - Journal Article
U2 - 10.1016/j.jhep.2016.07.050
DO - 10.1016/j.jhep.2016.07.050
M3 - Journal article
C2 - 27542322
SN - 0168-8278
VL - 65
SP - 1112
EP - 1119
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 6
ER -
