133 research outputs found
Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection Receiving Opioid Substitution Therapy: A Post Hoc Analysis of 12 Clinical Trials.
Background: We evaluated the impact of opioid substitution therapy (OST) on the completion, adherence, efficacy, and safety of the 3-direct-acting antiviral regimen of ombitasvir, paritaprevir (identified by AbbVie and Enanta) co-dosed with ritonavir, and dasabuvir ± ribavirin among patients infected with hepatitis C virus (HCV) genotype (GT) 1, with or without compensated cirrhosis. Methods: Data were pooled from GT1-infected patients enrolled in 12 phase II/III/IIIb clinical trials and categorized by use of OST. Patients with ongoing drug use were excluded. HCV treatment completion, treatment adherence (≥90%), sustained virologic response at post-treatment week 12 (SVR12), and adverse events were assessed. Results: Of 4747 patients, 3% (n = 149) received OST. Among patients receiving OST vs those not receiving OST, 82% (n = 122) vs 52% (n = 2409) had GT1a infection; 76% (n = 113) vs 61% (n = 2792) were treatment naïve; and 17% (n = 25) vs 18% (n = 830) had cirrhosis, respectively. The proportion of patients completing HCV treatment did not differ between those receiving and not receiving OST (97% [n = 144] vs 98% [n = 4510], respectively), whereas adherence to treatment was reduced in patients receiving vs those not receiving OST (88% [n = 105] vs 97% [n = 4057], respectively). SVR12 was similar between patients receiving and not receiving OST (94% [n = 140] vs 96% [n = 4405], respectively; P = .273). Treatment was well tolerated. Conclusions: Although treatment adherence was lower in patients receiving OST vs those not receiving OST, treatment completion and SVR12 were similar between groups. These data support the use of direct-acting antiviral therapies in patients receiving OST
Comparative effectiveness of 8 versus 12 weeks of Ombitasvir/Paritaprevir/ritonavir and Dasabuvir in treatment-naïve patients infected with HCV genotype 1b with non-advanced hepatic fibrosis
Advances in Treatment of Hepatitis C
Hepatitis C infection (HCV) is a major cause of chronic hepatitis and cirrhosis worldwide. Interferon-based regimen has been the sole therapy to eradicate HCV infection for decades. However, this interferon and ribavirin combination is associated with several serious adverse events and the sustained virologic response rate was suboptimal. The recent discovery of oral direct-acting antiviral agents (DAAs) heralded a revolution in the treatment of chronic HCV. This breakthrough in HCV resulted in high rates of HCV eradication with sustained virologic response rates ranging between 90 and 100% across different genotypes. New therapies were administered orally for 12 or 24 months and this resulted in better compliance and few adverse events. DAAs are categorized into four major groups namely: NS5B nucleotide inhibitors, NS5B nonnucleoside inhibitors, NS5A replication complex inhibitors, and NS3/4A protease inhibitors (PI). Several interferon-free regimens have been approved and adequately assessed and several new regimens with high potencies, less cross-resistance, and better safety profile are in the process of approval. Thus, the era of HCV eradication and cure has begun
Hepatitis C — Overview and Update in Treatment
Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide, making it a major public health issue. The World Health Organization (WHO) estimates a worldwide prevalence of 3%. Each year, three to four million people are newly diagnosed with HCV, and it remains endemic in many countries of the world. According to the WHO, there are at least 21.3 million HCV carriers in Eastern Mediterranean countries, a figure close to the combined number of estimated carriers in the Americas and Europe. The purpose of this chapter is to give an overview and update in treatment of HCV patients by a broad search of published literature on aspect of epidemiology, natural history, risk factors, diagnosis and treatment of HCV, graded on the best available evidence. All that to improve HCV patient care, and to promote and improve the multidisciplinary care required in the treatment of these patients
Drug–Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers
Current Therapeutic Options for HCV-HIV Coinfection
Due to shared risk factors for transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a very common event. The prevalence of HCV infection among HIV-positive patients averages about 35%. In HIV/HCV co-infected patients, liver-related morbidity and mortality is a prominent non-AIDS-defining complication: up to 90% of liver-related deaths in HIV-infected patients are attributable to HCV. The progression of liver fibrosis is accelerated in HIV/HCV-coinfected patients, particularly in individuals with low CD4 counts (≤350 cells/mm3). Antiretroviral therapy may slow liver disease progression in HIV/HCV-coinfected patients and should, therefore, be considered for all coinfected patients regardless of CD4 cell count. Most patients with HIV/HCV coinfection are taking multi-drug antiretroviral therapy, which may pose a problem with drug–drug interactions when initiating therapy with HCV medications. Rapid advances in HCV drug development led to the discovery of new classes of direct-acting antiviral (DAA) agents that target the HCV replication cycle. Several studies demonstrated comparable rates of sustained virological response (SVR) in coinfected and monoinfected patients with new DAA-based therapy
Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin
Background & Aims: Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.
Methods: We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.
Results: Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post-treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).
Conclusions: Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post-treatment. Patients with low baseline haemoglobin should be monitored for on-treatment anaemia
Incremental cost-effectiveness pharmacoeconomic assessment of hepatitis C virus therapy: an approach for less wealthy members of the common market
Aim To develop a new method of health-economic analysis
based on a marginal approach.
Methods We tested the research hypothesis that a detailed
comparative a priori incremental cost-effectiveness analysis
provides the necessary input for budget impact analysis
about the proper order of introduction of new therapies,
and thus maximizes the cost-effectiveness bounded
by the total budget constraint. For the analysis we chose a
combination therapy for the treatment of hepatitis C virus
(HCV) genotype 1 (GT1) infection, which was approved by
the European Medicine Agency in 2015. We used the incremental
cost-effective approach to assess the increase
in the percentage of patients achieving sustained virological
response (SVR) and the expenditure per additional SVR
modulated by the new therapy’s market entrance dynamics.
Patient subpopulations were differentiated by their response
to previous treatment, presence of cirrhosis, and
HCV GT1 subtype. Final parameters were estimated by
Monte Carlo simulations.
Results The new combination therapy had high efficacy,
shorter duration, and was better tolerated than alternative
interventions. The research hypothesis was confirmed:
gradual introduction of the new therapy on the market,
based on a priori incremental cost-effectiveness analysis,
would result in average increase in successfully treated patients
by 20%-40%, while additional costs would approximately
be between 8%-40%, ie, €21 000-52 000 per additional
patient achieving SVR.
Conclusion We showed the new combination therapy
to be cost-effective for certain patient subpopulations,
especially for experienced cirrhotic HCV GT1 patients. Results
of the analysis are in agreement with the latest recommendations
for HCV patients’ treatment in Croatia. This
economic evaluation could serve as a starting point for
negotiations between pharmaceutical industry and insurance
companies
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