Journal ArticleDOI
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem,Reem Ghalib,K. Rajender Reddy,Paul J. Pockros,Ziv Ben Ari,Yue Zhao,Deborah D. Brown,Shuyan Wan,Mark J. DiNubile,Bach-Yen Nguyen,Michael N. Robertson,Janice Wahl,Eliav Barr,Joan R. Butterton +13 more
TLDR
Grazoprevir and elbasvir were evaluated in a randomized, blinded, placebo-controlled trial in treatment-naive patients with hepatitis C virus (HCV) infection.Abstract:
BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.read more
Citations
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Journal ArticleDOI
Meta-analysis of the Efficacy and Safety of Grazoprevir and Elbasvir for the Treatment of Hepatitis C Virus Infection
TL;DR: Recently, the US Food and Drug Administration approved a fixed-dose combination of grazoprevir and elbasvir (GE), the new DAAs, for the treatment of HCV infection caused by genotype (GT) 1 or 4 viruses, with or without ribavirin (R).
Journal ArticleDOI
Hepatitis C: Down but Not Out.
TL;DR: These findings provide hope that HCV infection is now a fully treatable condition that, with sufficient efforts, can be eliminated as an important medical problem in the United States.
Journal ArticleDOI
Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study.
Ewa Janczewska,Mateusz Franciszek Kołek,Beata Lorenc,Jakub Klapaczyński,Magdalena Tudrujek-Zdunek,Marek Sitko,Włodzimierz Mazur,Dorota Zarębska-Michaluk,Iwona Buczyńska,Dorota Dybowska,Agnieszka Czauż-Andrzejuk,Hanna Berak,Rafał Krygier,Jerzy Jaroszewicz,Jolanta Citko,Anna Piekarska,Beata Dobracka,Łukasz Socha,Zbigniew Deroń,Łukasz Laurans,Jolanta Białkowska-Warzecha,Olga Tronina,Brygida Adamek,Krzysztof Tomasiewicz,Krzysztof Simon,Małgorzata Pawłowska,Waldemar Halota,Robert Flisiak +27 more
TL;DR: In this article, the authors analyzed factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting and found that the most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index.
Journal ArticleDOI
A profiling study of a newly developed HCVcc strain PR63cc's sensitivity to direct-acting antivirals
TL;DR: This study systemically analyzed the DAA sensitivity of a new HCVcc strain and identified critical RAVs not only important for monitoring the emergence of drug‐resistant mutations of current DAA therapies, but also valuable for developing next‐generation DAAs.
Journal ArticleDOI
Pharmacokinetic and pharmacodynamic evaluation of daclatasvir, asunaprevir plus beclabuvir as a fixed-dose co-formulation for the treatment of hepatitis C.
TL;DR: DCV-TRIO is neither pangenotypic nor potent enough against GT-1a, regardless of the presence or absence of cirrhosis, and this co-formulation might still have a place in the treatment of non-cirrhotic patients infected withGT-1b provided that massive access to treatment is facilitated.
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Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis
Kris V. Kowdley,Stuart C. Gordon,K. Rajender Reddy,Lorenzo Rossaro,David E. Bernstein,Eric Lawitz,Mitchell L. Shiffman,Eugene R. Schiff,Reem Ghalib,Michael J. Ryan,Vinod K. Rustgi,Mario Chojkier,Robert Herring,Adrian M. Di Bisceglie,Paul J. Pockros,G. Mani Subramanian,Di An,Evguenia S. Svarovskaia,Robert H. Hyland,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,David Pound,Michael W. Fried +24 more
TL;DR: Leadipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis, and results indicated noninferiority of the 8-week ledipas Viral-SofosBuvir regimen.
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Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.
Jordan J. Feld,Kris V. Kowdley,Eoin Coakley,Samuel H. Sigal,David R. Nelson,Darrell H. G. Crawford,Ola Weiland,Humberto Aguilar,Junyuan Xiong,Tami Pilot-Matias,Barbara DaSilva-Tillmann,Lois Larsen,Thomas Podsadecki,B. Bernstein +13 more
TL;DR: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.
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