Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection

Lawitz, Eric; Mangia, Alessandra; Wyles, David L.; Rodrı́guez-Torres, Maribel; Hassanein, Tarek; Gordon, Stuart C.; Schultz, Michael; Davis, Mitchell; Kayali, Zeid; Reddy, K. Rajender; Jacobson, Ira M.; Kowdley, Kris V.; Nyberg, Lisa M.; Subramanian, G. Mani; Hyland, Robert H.; Arterburn, Sarah; Jiang, Deyuan; McNally, John; Brainard, Diana M.; Symonds, William T.; McHutchison, John G.; Sheikh, Aasim; Younossi, Zobair M.; Gane, Edward

doi:10.1056/nejmoa1214853

Cited by 1,612 publications

(1,609 citation statements)

References 17 publications

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“…In the NEUTRINO trial, treatment-naive GT-1, 4, 5, and 6 patients who were treated for 12 weeks with SOF with Peg-IFNa/RBV, non-CC IL28B GT (SVR 12: 87% vs. 98%), and cirrhosis (80% vs. 92%) were significantly associated with reduced response on multivariate analysis. 19 Detection of liver fibrosis and cirrhosis: Though liver biopsy remains the 'gold standard,' liver cirrhosis is usually diagnosed on the basis of a combination of clinical, biochemical, sonographic, and endoscopic criteria. This approach is reliable for detecting compensated cirrhosis with portal hypertension but not in the absence of portal hypertension.…”

Section: Assessment Prior To Treatmentmentioning

confidence: 99%

“…Six trials have addressed the issue of SOF and RBV therapy, with or without Peg-IFNa, in the management of GT-1. These include the NIH SPARE, 30 ELECTRON, 31 NEUTRINO, 19 QUANTUM, 32 ATOMIC, 33 and PROTON 34 trials. All the trials enrolled treatmentnaive patients of GT-1, except for the one arm of treatment-experienced GT-1 patients in the ELECTRON trial (n = 10).…”

Section: Ns5b-i Ravsmentioning

confidence: 99%

See 1 more Smart Citation

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

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Section: Assessment Prior To Treatmentmentioning

confidence: 99%

Section: Ns5b-i Ravsmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…Regional differences in the cost of HCV therapies may lead to continued use of interferon-based regimens for the foreseeable future. Regimens that have been approved for treating genotype-1 infection include sofosbuvir plus PegIFN and RBV [35] and simeprevir plus PegIFN and RBV [25,27]. For patients ineligible for interferon, sofosbuvir plus simeprevir with or without RBV is recommended [36].…”

Section: Discussionmentioning

confidence: 99%

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection

Ferenci

Asselah

Foster

et al. 2015

Journal of Hepatology

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Background & Aims:The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. Methods: Patients were randomly assigned (1:2:2) to PegIFN/ RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Results: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p <0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. Conclusions: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg. Ó

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“…43 Total costs of HCV medication guidelines by the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) as of January 2015 with cure rates from clinical trials is summarized in Table 1. 28,29,44,31,32,45 For the purposes of calculating total medication costs, we assumed entirely interferon-free regimens with the highest SVRs from clinical trials across all genotypes, given the current community standard of care. For genotypes 1 and 4, we calculated total drug costs of a SOF/LDV regimen, with varying duration of 8 to 24 weeks based on fibrosis and treatment history for genotype 1 patients.…”

Section: Methodsmentioning

confidence: 99%

“…SVRs as high as 97 % were achieved in genotype 2 patients with SOF+RBV combination therapy. 28,29 In the fall of 2014, SOF and ledipasvir (LDV) together were approved as a fixed-dosed combination and SOF+SMV were approved as combination therapy. More recently, the FDA has approved the co-formulated ombitasvir, paritaprevir, and ritonavir with dasabuvir regimen (OBV/PTV/r+DSV) for genotype 1 patients and those with advanced cirrhosis, also eliminating RBV in some cases.…”

Section: Introductionmentioning

confidence: 99%

A Budget Impact Analysis of Newly Available Hepatitis C Therapeutics and the Financial Burden on a State Correctional System

et al. 2015

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Hepatitis C virus (HCV) infection continues to disproportionately affect incarcerated populations. New HCV drugs present opportunities and challenges to address HCVin corrections. The goal of this study was to evaluate the impact of the treatment costs for HCV infection in a state correctional population through a budget impact analysis comparing differing treatment strategies. Electronic and paper medical records were reviewed to estimate the prevalence of hepatitis C within the Rhode Island Department of Corrections. Three treatment strategies were evaluated as follows: (1) treating all chronically infected persons, (2) treating only patients with demonstrated fibrosis, and (3) treating only patients with advanced fibrosis. Budget impact was computed as the percentage of pharmacy and overall healthcare expenditures accrued by total drug costs assuming entirely interferon-free therapy. Sensitivity analyses assessed potential variance in costs related to variability in HCV prevalence, genotype, estimated variation in market pricing, length of stay for the sentenced population, and uptake of newly available regimens. Chronic HCV prevalence was estimated at 17 % of the total population. Treating all sentenced inmates with at least 6 months remaining of their sentence would cost about $34 million-13 times the pharmacy budget and almost twice the overall healthcare budget. Treating inmates with advanced fibrosis would cost about $15 million. A hypothetical 50 % reduction in total drug costs for future therapies could cost $17 million to treat all eligible inmates. With immense costs projected with new treatment, it is unlikely that correctional facilities will have the capacity to treat all those afflicted with HCV. Alternative payment strategies in collaboration with outside programs may be necessary to curb this epidemic. In order to improve care and treatment delivery, drug costs also need to be seriously reevaluated to be more accessible and equitable now that HCV is more curable.

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Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection

Cited by 1,612 publications

References 17 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection

A Budget Impact Analysis of Newly Available Hepatitis C Therapeutics and the Financial Burden on a State Correctional System

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