Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine

Lalezari, Jacob; Sullivan, J. Greg; Varunok, Peter; Galen, Edward; Kowdley, Kris V.; Rustgi, Vinod K.; Aguilar, Humberto; Felizarta, Franco; McGovern, Barbara; King, Martin; Polepally, Akshanth R.; Cohen, Daniel E.

doi:10.1016/j.jhep.2015.03.029

Cited by 120 publications

(93 citation statements)

References 35 publications

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“…The comparable SVR12 outcomes in this post hoc analysis are consistent with previous data of interferon-based HCV therapy [7][8][9] and interferon-free DAA therapy for chronic HCV G1 among people receiving OST [10][11][12]. However, this study adds considerably to the literature, given that almost all studies of DAA therapy among people receiving OST are restricted to people with HCV G1, G4, or G6.…”

Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

et al. 2016

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In this analysis of the ASTRAL trials (non-opioid substitution therapy [OST], n = 984; OST, n = 51) evaluating the once-daily, pan-genotypic regimen of sofosbuvir/velpatasvir for hepatitis C virus infection, OST did not impact completion, adherence, sustained virologic response (SVR12), or safety. SVR12 was 96% (95% confidence interval, 87%, >99%) in those receiving OST.Keywords. HCV; OST; PWID; sofosbuvir; velpatasvir.People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infection [1]. People with a history of injection drug use include those who have stopped injecting, those with recent injecting, and those receiving opioid substitution therapy (OST; eg, methadone or buprenorphine), some of whom may also have recently injected drugs. Data are lacking on HCV treatment outcomes with interferon-free direct-acting antiviral agents (DAAs) among people receiving OST, particularly people with genotypes (G) other than HCV G1. The phase 3 ASTRAL 1-3 trials evaluated the efficacy and safety of sofosbuvir/velpatasvir in patients with chronic HCV genotypes 1-6 [2, 3]. People receiving stable OST were eligible for inclusion, but people with clinically relevant illicit drug use within 12 months or a positive urine drug test at screening were excluded. No drug screens were performed during or following treatment. These clinical trial populations are highly selected, included people on stable OST, excluded people with recent drug use, and may not be representative of recent PWID populations. However, there are little data on interferon-free DAA therapy among people receiving OST.The aim of this post hoc analysis was to evaluate treatment completion, adherence, sustained virologic response (SVR), and safety of sofosbuvir/velpatasvir in people receiving OST without drug use at screening. METHODS Study Participants and DesignFrom 18 July 2014 to 19 December 2014 participants were enrolled in 3 international, multicenter, randomized open-label trials, including ASTRAL 1-3 (ClinicalTrials.gov: NCT02201940, NCT02220998, and NCT02201953) [2,3]. A fixed-dose combination tablet of sofosbuvir/velpatasvir 400 mg/100 mg was administered for 12 weeks in patients with chronic HCV genotypes 1-6. These studies have been described previously [2,3].Participants receiving OST were eligible for inclusion in the ASTRAL studies. Patients were excluded if they had clinically significant drug use within 12 months of screening (as assessed by the investigator) or a noncannabinoid detected by a positive urine drug test during the screening phase not explained by a prescription medication. No drug screens were performed during or following treatment. Study EndpointsIn this analysis, endpoints included treatment completion, adherence (≥90% of doses), SVR12, safety (adverse events [AEs] and serious AEs), and reinfection. The analysis population included all randomized patients who received at least 1 dose of sofosbuvir/velpatasvir. Adherence was calculated by dividing the number of total doses received during therapy...

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Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

et al. 2016

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“…High SVR rate (95-98%) with good safety and tolerability has been reported in patients with sickle cell anemia or β-thalasemia in the C-EDGE IBLD study [50]. The indications and regimens of anti-HCV therapy are the same in patients with and without hemoglobinopathies [A1] apart from the fact that they should be treated without RBV [B1].…”

Section: Hemoglobinopathies and Bleeding Disordersmentioning

confidence: 99%

“…In inherited bleeding disorders such as hemophilia, the management of chronic HCV infection is similar to the nonhemophilic population (indications, regimens) [A1] and DAAs therapy is associated with high SVR rates (91%) [50].…”

Section: Hemoglobinopathies and Bleeding Disordersmentioning

confidence: 99%

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

Gheorghe

Sporea

Iacob

et al. 2017

JGLD

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Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

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“…Abbreviation: CV, coefficient of variation.*N = 11 for AUC and C trough of ombitasvir, paritaprevir, and ritonavir.†Range of geometric means from three studies in adults infected with HCV who had intensive pharmacokinetic data(29) (and AbbVie data on file).‡AUC 0‐24hour for ombitasvir, paritaprevir, and ritonavir; AUC 0‐12hour for dasabuvir.…”

Section: Resultsmentioning

confidence: 99%

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

Leung

Wirth

Yao

et al. 2018

Hepatology Communications

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In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

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Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine

Cited by 120 publications

References 35 publications

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

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