Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis

Gastroenterology

Volumn 152, Issue 6, 2017, Pages 1372-1382.e2

  Jacobson, Ira M ^a   Lawitz, Eric ^b   Kwo, Paul Y ^c   Hézode, Christophe ^d   Peng, Cheng Yuan ^e   Howe, Anita Y M ^f   Hwang, Peggy ^f   Wahl, Janice ^f   Robertson, Michael ^f   Barr, Eliav ^f   Haber, Barbara A ^f  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^c INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d HENRI MONDOR HOSPITAL   (France)

^e CHINA MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^f MERCK RESEARCH LABORATORIES   (United States)

Author keywords

ALT; Fibrosis; NS5A; Virus Mutation

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; ELBASVIR PLUS GRAZOPREVIR; NONSTRUCTURAL PROTEIN 5A; RIBAVIRIN; VIRUS RNA; 2-(PYRROLIDIN-2-YL)-5-(2-(4-(5-(PYRROLIDIN-2-YL)-1H-IMIDAZOL-2-YL)PHENYL)BENZOFURAN-5-YL)-1H-IMIDAZOLE; ANTIVIRUS AGENT; BENZOFURAN DERIVATIVE; DRUG COMBINATION; IMIDAZOLE DERIVATIVE; MK-5172; NS-5 PROTEIN, HEPATITIS C VIRUS; QUINOXALINE DERIVATIVE; VIRAL PROTEIN;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL THERAPY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; COLITIS; CONTROLLED CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; DECOMPENSATED LIVER CIRRHOSIS; DEPRESSION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; FEMALE; HEADACHE; HEPATITIS C; HEPATITIS C VIRUS GENOTYPE 1; HEPATITIS C VIRUS GENOTYPE 4; HEPATITIS C VIRUS GENOTYPE 6; HUMAN; INSOMNIA; LIVER CIRRHOSIS; LYMPHOMA; MAJOR CLINICAL STUDY; MALE; NAUSEA; PORTAL VEIN THROMBOSIS; PRIORITY JOURNAL; RASH; SUSTAINED VIROLOGIC RESPONSE; TACHYCARDIA; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; UTERUS BLEEDING; ANTIVIRAL RESISTANCE; BLOOD; COMBINATION DRUG THERAPY; COMPLICATION; DRUG COMBINATION; GENETICS; HEPACIVIRUS; HEPATITIS C, CHRONIC; MIDDLE AGED; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RETREATMENT; RETROSPECTIVE STUDY; VERY ELDERLY; VIROLOGY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; ANTIVIRAL AGENTS; BENZOFURANS; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG COMBINATIONS; DRUG RESISTANCE, VIRAL; DRUG THERAPY, COMBINATION; FEMALE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; IMIDAZOLES; LIVER CIRRHOSIS; MALE; MIDDLE AGED; QUINOXALINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RETREATMENT; RETROSPECTIVE STUDIES; RIBAVIRIN; RNA, VIRAL; SUSTAINED VIROLOGIC RESPONSE; VIRAL NONSTRUCTURAL PROTEINS; YOUNG ADULT;

EID: 85018219352     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2017.01.050     Document Type: Article

References (31)

1. 1 Thein, H.-H., Yi, Q., Dore, G.J., et al. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology 48 (2008), 418–431.
2. 2 Xu, F., Moorman, A.C., Tong, X., et al., for the Chronic Hepatitis Cohort Study (CHeCS) Investigators. All-cause mortality and progression risks to hepatic decompensation and hepatocellular carcinoma in patients infected with hepatitis C virus. Clin Infect Dis 62 (2016), 289–297.
3. 3 Davis, G.L., Alter, M.J., El-Serag, H., et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138 (2010), 513–521.e6.
4. 4 Kutala, B.K., Guedj, J., Asselah, T., et al. Impact of treatment against hepatitis C virus on overall survival of naive patients with advanced liver disease. Antimicrob Agents Chemother 59 (2015), 803–810.
5. 5 Nyberg LM, Li X, Yang S-J, et al. The association of sustained virological response and all-cause mortality after interferon-based therapy for chronic hepatitis C (HCV) in a large U.S. community-based health care delivery system. Presented at The Liver Meeting 2015, November 13−17, 2015; San Francisco, CA.
6. 6 Hézode, C., Fontaine, H., Dorival, C., et al. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. Gastroenterology 147 (2014), 132–142.e4.
7. 7 Shiffman, M.L., Di Bisceglie, A.M., Lindsay, K.L., et al., and The HALT-C Trial Group. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 126 (2004), 1015–1023.
8. 8 European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol 66 (2017), 153–194.
9. 9 American Association for the Study of Liver Diseases/Infectious Disease Society of North America Web site. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Full report. Available at: http://www.hcvguidelines.org/full-report-view. Accessed August 23, 2016.
10. 10 Rockstroh, J.K., Nelson, M., Katlama, C., et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV 2 (2015), e319–e327.
11. 11 Zeuzem, S., Ghalib, R., Reddy, K.R., et al. Grazoprevir-elbasvir combination therapy for treatment–naive cirrhotic and noncirrhotic patients with chronic HCV genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 163 (2015), 1–13.
12. 12 Roth, D., Nelson, D.R., Bruchfeld, A., et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4−5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 386 (2015), 1537–1545.
13. 13 Forns, X., Gordon, S.C., Zuckerman, E., et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol 63 (2015), 564–572.
14. 14 Lawitz, E., Gane, E., Pearlman, B., et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 385 (2015), 1075–1086.
15. 15 Sulkowski, M., Hezode, C., Gerstoft, J., et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 385 (2015), 1087–1097.
16. 16 Summa, V., Ludmerer, S.W., McCauley, J.A., et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother 56 (2012), 4161–4167.
17. 17 Coburn, C.A., Meinke, P.T., Chang, W., et al. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem 8 (2013), 1930–1940.
18. 18 Lahser F, Liu R, Bystol K, et al. A combination containing MK-5172 (HCV N53 protease inhibitor) and MK-8742 (HCV NS5A inhibitor) demonstrates high barrier to resistance in HCV replicons. Presented at: The Liver Meeting 2012; November 9−13, 2012; Boston, MA.
19. 19 Kwo, P., Gane, E., Peng, C.-Y., et al. Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology 152 (2017), 164–175.e4.
20. 20 Dusheiko GM, Manns MP, Vierling JM, et al. Safety and tolerability of elbasvir/grazoprevir in patients with chronic hepatitis C: an integrated analysis of phase 2−3 trials. Presented at The Liver Meeting 2015, November 13-17, 2015; San Francisco, CA.
21. 21 Manns, M.P., Vierling, J.M., Bacon, B.R., et al. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology 147 (2014), 366–376.
22. 22 Buti, M., Gordon, S.C., Zuckerman, E., et al. Grazoprevir, elbasvir, and ribavirin for chronic hepatitis C virus genotype 1 infection after failure of pegylated interferon and ribavirin with an earlier-generation protease inhibitor: final 24-week results from C-SALVAGE. Clin Infect Dis 62 (2016), 32–36.
23. 23 Jacobson, I.M., Asante-Appiah, E., Wong, P., et al. Prevalence and impact of baseline-NS5A resistance associated variants (RAVs) on the efficacy of elbasvir/grazoprevir (EBR/GZR) against GT1a infection. Hepatology, 62, 2015, 1393A.
24. 24 Sarrazin, C., Dvory-Sobol, H., Svarovskaia, E.S., et al. Prevalence of resistance-associated substitutions in HCV NS5A, NS5B, or NS3 and outcomes of treatment with ledipasvir and sofosbuvir. Gastroenterology 151 (2016), 501–512.
25. 25 Reddy, K.R., Bourlière, M., Sulkowski, M., et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: an integrated safety and efficacy analysis. Hepatology 62 (2015), 79–86.
26. 26 Harvoni [package insert], 2014, Gilead Sciences Inc, Foster City, CA.
27. 27 Bourlière, M., Bronowicki, J.-P., de Ledinghen, V., et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 15 (2015), 397–404.
28. 28 Poordad, F., Hezode, C., Trinh, R., et al. ABT-450/r–ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 370 (2014), 1973–1982.
29. 29 Viekira XR [package insert], 2016, AbbVie Inc, North Chicago, IL.
30. 30 Epclusa [package insert], 2016, Gilead Sciences Inc, Foster City, CA.
31. 31 Zepatier [package insert], 2016, Merck & Co, Inc, Whitehouse Station, NJ.