The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection

• Published in: Journal of gastroenterology 2018-05, Vol.53 (5), p.679-688
• Main Authors: Zeuzem, Stefan, Serfaty, Lawrence, Vierling, John, Cheng, Wendy, George, Jacob, Sperl, Jan, Strasser, Simone, Kumada, Hiromitsu, Hwang, Peggy, Robertson, Michael, Wahl, Janice, Barr, Eliav, Talwani, Rohit, Platt, Heather
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adolescent; Adult; Aged; Amides; Analysis; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Benzofurans - adverse effects; Benzofurans - therapeutic use; Biliary Tract; Biological products industry; Carbamates; Chronic infection; Cirrhosis; Clinical trials; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Coinfection - complications; Colorectal Surgery; Cyclopropanes; Data processing; Drug Resistance, Viral - genetics; Female; Gangliosides; Gastroenterology; Genetic aspects; Genotype; Genotypes; Health aspects; Hepacivirus - genetics; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Hepatology; HIV Infections - complications; Humans; Imidazoles - adverse effects; Imidazoles - therapeutic use; Infection; Infections; Liver cirrhosis; Liver Cirrhosis - physiopathology; Liver Cirrhosis - virology; Male; Medical colleges; Medicine; Medicine & Public Health; Middle Aged; Original Article—Liver; Pancreas; Quinoxalines - adverse effects; Quinoxalines - therapeutic use; Retrospective Studies; Ribonucleic acid; RNA; Sulfonamides; Surgical Oncology; Sustained Virologic Response; Viral Load; Viral Nonstructural Proteins - genetics; Young Adult
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-018-1429-3

Background Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. Methods This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The primary end point of all studies was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA  800,000 IU/ml (705/728, 96.8%). Resistance-associated substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of participants at baseline. SVR12 was 99.6% (820/823) in participants without baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred after study medication was completed. Conclusions Elbasvir/grazoprevir for 12 weeks represents an effective treatment option for participants with HCV GT1b infection. SVR12 was high in all participant subgroups, including those with compensated cirrhosis, HIV co-infection, and high baseline viral load. ClinicalTrials.gov identifiers The trials discussed in this paper were registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER), NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive), NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990 (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C-SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).