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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The cost-effectiveness of testing for NS5a resistance-associated polymorphisms at baseline in genotype 1a-infected (treatment-naïve and treatment-experienced) subjects treated with all-oral elbasvir/grazoprevir regimens in the United States.
TL;DR: The presence of baseline NS5A resistance‐associated variants (RAVs) impacted treatment response in HCV genotype 1a (GT1a)‐infected patients treated with elbasvir/grazoprevir (EBR/GZR) for 12 weeks, but not patientstreated with EBR/ GZR and ribavirin (RBV) for 16 weeks.
Journal ArticleDOI
Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don't Change a Thing
TL;DR: How the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use are discussed.
Journal ArticleDOI
Current and Evolving Treatments of Genotype 1 Hepatitis C Virus.
TL;DR: The field of direct-acting antiviral therapies for HCV infection continues to advance at a rapid pace, and many more potential treatment regimens are being investigated.
Journal ArticleDOI
Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan.
Zobair M. Younossi,Zobair M. Younossi,Atsushi Tanaka,Yuichiro Eguchi,Linda Henry,R. Beckerman,Masashi Mizokami +6 more
TL;DR: Treatment of HCV GT1b with all‐oral direct‐acting anti‐virals in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.
Journal ArticleDOI
Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.
Lucia Macken,Lucia Macken,William Gelson,M. Priest,G. Abouda,Stephen T. Barclay,Andrew Fraser,Brendan Healy,William L. Irving,Sumita Verma,Sumita Verma +10 more
TL;DR: This real‐world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post‐treatment, with lower baseline serum creatinine being associated with recompensation.
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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
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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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