Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection

Sulkowski, Mark S.; Gardiner, David F.; Rodrı́guez-Torres, Maribel; Reddy, K. Rajender; Hassanein, Tarek; Jacobson, Ira M.; Lawitz, Eric; Lok, Anna S.; Hinestrosa, Federico; Thuluvath, Paul J.; Schwartz, Howard; Nelson, David R.; Everson, Gregory T.; Eley, Timothy; Wind‐Rotolo, Megan; Huang, Shenlin; Gao, Min; Hernandez, Dennis; McPhee, Fiona; Sherman, Diane L.; Hindes, R.; Symonds, William T.; Pasquinelli, Claudio; Grasela, Dennis M.

doi:10.1056/nejmoa1306218

Cited by 1,093 publications

(885 citation statements)

References 30 publications

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“…Sulkowski et al 54 evaluated the role of DCV/SOF with or without RBV in HCV in the AI444-040 trial. In part 1 of the trial, 88 treatment-naive patients (44 with GT-1 and 44 with GT-2 or 3) were treated with DCV/SOF, with or without weight-based RBV for 24 weeks.…”

Section: Genotypementioning

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: Genotypementioning

confidence: 99%

“…23,54 While SOF/RBV therapy has excellent efficacy in HCV GT-2, many patients may not be able to tolerate RBV. These patients may benefit from combination therapy with DCV and SOF.…”

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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“…Ezzel együtt, daclatasvir és proteáz gátló kombinációja esetén mindenképpen indokolt a leggyakoribb mutánsok szűrővizsgálata, mert jelenlétükben az SVR csak 40%, míg ha ilyen bázispoli-morfi zmus nem észlelhető, az SVR 80% feletti [25]. A daclatasvir-sofosbuvir kombináció esetén a bázispoli-morfi zmus jelentősége viszont teljesen elhanyagolható és előszűrése nem ajánlott [26].…”

Section: Ns5a-gátlókunclassified

“…A rezisztens mutánsok elvben kimutathatatlanná válhat-tak, mégis elsősorban olyan kombináció preferálandó, amelyben nincsen NS3/4A proteázgátló, a lehetséges keresztrezisztencia miatt. A sofosbuvir-daclatasvir, illetve a sofosbuvir-ledipasvir kombináció viszont egyaránt kifejezetten hatékony volt ebben a betegcsoportban [26,27]. A paritaprevir-dasabuvir-ombitasvir kombinációval egyelőre ebben a betegcsoportban még nem állnak rendelkezésre adatok.…”

Section: Hcv-bázispolimorfi Zmus éS Gyógyszer-rezisztencia a Klinikaiunclassified

A hepatitis C-vírus-bázispolimorfizmus jelentősége a kezelésben

Tornai

2015

Orvosi Hetilap

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A krónikus C-vírus hepatitis kezelése az elmúlt huszonöt évben igen jelentős fejlődésen ment keresztül. Az 1-es genotípusú betegek gyógyulási aránya a pegilált interferon és ribavirin kettős kombinációval elérhető 40-50%-ról a direkt ható antivirális szerek bevezetésével szignifi kánsan növekedett. A direkt ható antivirális szerek három nagy csoportja ismert, amelyek a vírus szaporodásának különböző fázisában fejtik ki hatásukat, a vírus nem strukturális fehérjéinek működését gátolják (NS3/4A proteáz, NS5A protein és NS5B polimeráz). A hepatitis C-vírus rendkívül gyorsan szaporodik és ennek kapcsán folyamatosan képződnek mutánsok, amelyek rezisztensek lehetnek a direkt ható antivirális terápiára. Mivel a kezelés előtt ezek már jelen lehetnek, és a direkt ható antivirális kezelés alatt csak ezek képesek szaporodni, a szelekciós nyomás hatására a rezisztens vírus váltja fel a vad típust. Ez különösen megfi gyelhető volt monoterápia esetén, emiatt a direkt ható antivirális szereket kezdetben pegilált interferonnal kombinálták, majd mostanában teljesen interferonmentes kezeléseket fejlesztettek ki, amelyek két vagy három direkt ható antivirá-lis szer kombinációjából állnak. Az első generációs proteázgátló telaprevir és boceprevir mellett megfi gyelhető volt, hogy az 1a genotípusú betegek kedvezőtlenebbül reagálnak, magasabb a rezisztenciaarány, mint az 1b-betegekben. Hasonló jelenség megfi gyelhető a korszerűbb proteázgátlókkal is, de az NS5A-és NS5B-gátlók esetén is. Ennek hátterében az alacsonyabb genetikai korlát áll, azaz kevesebb mutáció is elegendő a rezisztencia kialakulásához az 1a genotípusban. A szelektálódó rezisztens mutánsok jelentik az egyik legfontosabb kihívást az interferonmentes kezelések során. Orv. Hetil., 2015, 156(21), 849-854.Kulcsszavak: hepatitis C-vírus, direkt ható antivirális szerek, rezisztencia, genotípus 1a és 1b Signifi cance of hepatitis C virus baseline polymorphism during the antiviral therapyThe treatment of chronic hepatitis C has developed signifi cantly during the last 25 years. In patients with genotype 1 infection 40-50% sustained virologic response could be achieved using pegylated interferon and ribavirin dual combination, which could be increased signifi cantly with the introduction of direct acting antivirals. Three major groups of direct acting antivirals are known, which directly inhibit different phases of viral life cycle, by inhibiting the function of several non-structural proteins (NS3/4A protease, NS5A protein and NS5B polymerase). Due to the rapid replication rate of hepatitis C virus and the error-prone NS5B polymerase activity, mutant virions are generated, which might have reduced susceptibility to direct acting antiviral therapy. Since these resistance associated variants might exist before the antiviral therapy, they are still able to replicate during the direct acting antiviral treatment. Due to this selection pressure, the resistant virus will replace the wild type. This was especially detected during monotherapy, therefore, the fi rst generation of direct...

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“…[30][31][32] These therapies, and others anticipated over the next 1-2 years, bring the probability of cure to greater than 90 % for most patients and genotypes and have made interferon-free therapy the standard for HCV treatment. [33][34][35] These all-oral therapies come, however, at a substantial cost, with SOF individually priced as high as $84,000 and SOF/LDV priced at $94,500, both for a 12-week course. 36,37 SMV was priced comparably at $66,000 for 12 weeks making the total cost of SOF/SMV combination therapy up to $150,000.…”

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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Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection

Cited by 1,093 publications

References 30 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

A hepatitis C-vírus-bázispolimorfizmus jelentősége a kezelésben

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

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