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
Direct-acting antivirals: the endgame for hepatitis C?
TL;DR: Directly-acting antivirals have finally allowed all patients to be potentially cured from chronic hepatitis C (HCV) infection and availability of potent and safe antiviral drugs combined with improvement of worldwide access to treatment could finally lead to HCV elimination in the next decades.
Book ChapterDOI
Overview of Direct-Acting Antiviral Drugs and Drug Resistance of Hepatitis C Virus.
Darrick K. Li,Raymond T. Chung +1 more
TL;DR: It is anticipated that the incidence of treatment failure will continue to decrease in frequency with the development of drug regimens with increasing potency, barrier to resistance, and genotypic efficacy.
Journal ArticleDOI
Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
Velia Chiara Di Maio,Valeria Cento,Ilaria Lenci,Marianna Aragri,Piera Rossi,Silvia Barbaliscia,M. Melis,Gabriella Verucchi,Carlo Magni,Elisabetta Teti,Ada Bertoli,F.P. Antonucci,Maria Concetta Bellocchi,Valeria Micheli,C. Masetti,Simona Landonio,Simona Francioso,Francesco Santopaolo,Adriano M. Pellicelli,Vincenza Calvaruso,Laura Gianserra,Massimo Siciliano,Dante Romagnoli,Raffaele Cozzolongo,Antonio Grieco,Jacopo Vecchiet,Filomena Morisco,Manuela Merli,Giuseppina Brancaccio,Antonio Di Biagio,Elisabetta Loggi,Claudio Maria Mastroianni,Valeria Pace Palitti,Pierluigi Tarquini,Massimo Puoti,Gloria Taliani,Loredana Sarmati,Antonino Picciotto,Vincenzo Vullo,Nicola Caporaso,M. Paoloni,Caterina Pasquazzi,Giuliano Rizzardini,Giustino Parruti,Antonio Craxì,Sergio Babudieri,Massimo Andreoni,Mario Angelico,Carlo Federico Perno,Francesca Ceccherini-Silberstein +49 more
TL;DR: This study aimed to characterize the presence of clinically relevant RASs to all classes in real‐life DAA failures, and found that all classes of DAA patients had at least one RAS in their treatment regimens.
Journal ArticleDOI
Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature.
TL;DR: New DILI biomarkers, specifically microRNA-122 and keratin-18, appear to have the necessary predictive value to determine the prognosis and outcome of patients with paracetamol-induced acute liver failure (ALF), and may be of great benefit in deciding who requires N-acetylcysteine (NAC), and for what duration.
Journal ArticleDOI
Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis
Ira M. Jacobson,Eric Lawitz,Paul Y. Kwo,Christophe Hézode,Cheng Yuan Peng,Anita Y. M. Howe,Peggy Hwang,Janice Wahl,Michael N. Robertson,Eliav Barr,Barbara Haber +10 more
TL;DR: Baseline tests for resistance-associated substitutions (RASs) led to an individualized approach for selecting treatment duration and established a need for ribavirin for patients with HCV genotype 1a infection and RASs, regardless of treatment history.
References
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The use of confidence or fiducial limits illustrated in the case of the binomial
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Sofosbuvir for previously untreated chronic hepatitis C infection
Eric Lawitz,Alessandra Mangia,David L. Wyles,Maribel Rodriguez-Torres,Tarek Hassanein,Stuart C. Gordon,Michael Schultz,M. Davis,Zeid Kayali,K. Rajender Reddy,Ira M. Jacobson,Kris V. Kowdley,L. Nyberg,G. Mani Subramanian,Robert H. Hyland,Sarah Arterburn,Deyuan Jiang,John McNally,Diana M. Brainard,William T. Symonds,John G. McHutchison,Aasim Sheikh,Zobair M. Younossi,Edward Gane +23 more
TL;DR: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks.
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Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Nezam H. Afdhal,Stefan Zeuzem,Paul Y. Kwo,Mario Chojkier,Norman Gitlin,Massimo Puoti,Manuel Romero-Gómez,Jean-Pierre Zarski,Kosh Agarwal,Peter Buggisch,Graham R. Foster,Norbert Bräu,Maria Buti,Ira M. Jacobson,G. Mani Subramanian,Xiao Ding,Hongmei Mo,Jenny C. Yang,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,Alessandra Mangia,Patrick Marcellin +23 more
TL;DR: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection.
Journal ArticleDOI
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.
Journal ArticleDOI
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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