Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis

Kowdley, Kris V.; Gordon, Stuart C.; Reddy, K. Rajender; Rossaro, Lorenzo; Bernstein, David; Lawitz, Eric; Shiffman, Mitchell L.; Schiff, Eugene R.; Ghalib, Reem; Ryan, Michael J.; Rustgi, Vinod K.; Chojkier, Mario; Herring, Robert; Bisceglie, Adrian M. Di; Pockros, Paul J.; Subramanian, G. Mani; An, Di; Svarovskaia, Evguenia S.; Hyland, Robert H.; Pang, Phillip S.; Symonds, William T.; McHutchison, John G.; Muir, Andrew J.; Pound, David; Fried, Michael

doi:10.1056/nejmoa1402355

Cited by 1,042 publications

(964 citation statements)

References 11 publications

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“…The ION-3 study 48 (647 treatment-naive noncirrhotic patients) evaluated the role of further shortening the duration of LDV/SOF therapy (12 weeks vs. 8 weeks, with or without RBV), while SVR rates were 93 to 95% across all arms. However, for patients with HCV RNA of more than 6 million international Units (IU)/ml, relapse rates were higher with 8-week therapy compared to 12-week therapy in the RBV free arms.…”

Section: Genotypementioning

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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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: Genotypementioning

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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“…Safety and efficacy of SOF‐containing HCV regimens have been formally evaluated in over 10,000 patients in registration studies5, 6 and real‐world cohorts 7, 8, 9. Overall, the use of SOF appears safe with few significant toxicities reported.…”

Section: Introductionmentioning

confidence: 99%

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Cox-North

Hawkins

Rossiter

et al. 2017

Hepatology Communications

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Sofosbuvir (SOF) is a nonstructural 5B polymerase inhibitor with activity in all hepatitis C virus (HCV) genotypes and is the backbone of many anti‐HCV drug regimens. SOF is converted into inactive metabolites that undergo renal excretion. Patients with an estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 may experience increased drug exposure and thus potential toxicities along with decreased efficacy due to dose reduction or drug discontinuation. This is a single‐center study evaluating safety and effectiveness of SOF‐based regimens in patients with severe renal dysfunction, defined as eGFR <30 mL/minute/1.73 m2, including those receiving concurrent hemodialysis. Data were collected from patients with HCV and severe renal dysfunction who started full‐dose (400 mg) SOF‐based antiviral therapy ± ribavirin between April 2014 and February 2016. Medical records were reviewed for demographics, medical history, laboratory, radiologic imaging, echocardiography, transplant status, and liver pathologic findings. Twenty‐nine patients were identified; 12 had cirrhosis and 4 of those had decompensated cirrhosis. Fourteen patients had undergone transplantation of liver and/or kidney and were on calcineurin inhibitors, with 42% requiring dose increases or decreases while on therapy. All patients attained viral suppression on treatment, and 97% had a sustained viral response at 12 weeks posttreatment. There were no early treatment discontinuations. One death occurred posttreatment from a non‐ST elevation myocardial infarction in a patient with a history of coronary artery disease and ischemic cardiomyopathy. Conclusion: SOF‐based regimens appear safe in a broad range of patients with severe renal dysfunction, including those with decompensated cirrhosis and liver transplant. To confirm these retrospective findings, prospective studies that include SOF and SOF metabolite measurements coupled with prospective serial monitoring of electrocardiograms and echocardiograms are needed. (Hepatology Communications 2017;1:248‐255)

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“…The efficacy of treatment is based on clinical trial data, with successful treatment defined as a sustained viral response (SVR) at 12 weeks after the end of therapy 13, 14. Calculation of SVR rates is shown in Supporting Information Appendix 6.…”

Section: Methodsmentioning

confidence: 99%

Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in medicare and non‐medicare populations

Wittenborn

Brady

Dougherty

et al. 2017

Hepatology Communications

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We forecast the health and budgetary impact of hepatitis C (HCV) treatment on the Medicare program based on currently observed rates of treatment among Medicare and non‐Medicare patients and identify the impact of higher rates of treatment among non‐Medicare populations. We developed a computer microsimulation model to conduct an epidemiologic forecast, a budgetary impact analysis, and a cost‐effectiveness analysis of the treatment of HCV based on three scenarios: 1) no treatment, 2) continuation of current‐treatment rates, and 3) treatment rates among non‐Medicare patients increased to match that of Medicare patients. The simulated population is based on National Health and Nutrition Examination Survey data. HCV progression rates and costs were calculated in Surveillance, Epidemiology, and End Results Program Medicare 5% claims data from the Chronic Hepatitis Cohort Study and published literature. We estimate that 13.6% of patients with HCV in the United States are enrolled in Medicare, but 75% will enter Medicare in the next 20 years. Medicare patients were over 5 times as likely to be treated in 2014‐2015 as other patients. Medicare paid over $9 billion in treatment costs in both 2015 and 2016 and will total $28.4 billion from 2017‐2026. Increasing treatment rates among non‐Medicare patients would lead to 234,000 more patients being treated, reduce HCV mortality by 19%, and decrease Medicare costs by $18.6 billion from 2017‐2026. We find that treatment remains cost‐effective under most assumptions, costing $31,718 per quality adjusted life year gained. Conclusion: Medicare treats a disproportionately large share of HCV patients. Continued low rates of treatment among non‐Medicare HCV patients will result in both reduced and deferred treatment, shifting future treatment costs to Medicare while increasing overall medical management costs, morbidity, and mortality. (Hepatology Communications 2017;1:99‐109)

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Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis

Cited by 1,042 publications

References 11 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

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in medicare and non‐medicare populations

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