Absolute and relative contraindications to pegylated‐interferon or ribavirin in the <scp>US</scp> general patient population with chronic hepatitis C: results from a <scp>US</scp> database of over 45 000 <scp>HCV</scp>‐infected, evaluated patients

Talal, Andrew H.; LaFleur, Joanne; Hoop, Robert; Pandya, Prashant; Martin, Paul; Jacobson, Ira M.; Han, Jian; Korner, Eli J.

doi:10.1111/apt.12200

Cited by 44 publications

(46 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The addition of first-generation PIs in 2012 had very little impact on HCV disease burden. This was due to insufficient increase in SVR rates, restriction of access to G1, low treatment uptake, and frequent adverse events leading to dose reductions or cessation of treatment [36,39,46]. Table II.…”

Section: Discussionmentioning

confidence: 99%

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

Duberg

Blach

Falconer

et al. 2014

Scandinavian Journal of Gastroenterology

View full text Add to dashboard Cite

Objective. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies. Material and methods. HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections. Results. With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030. Conclusion. Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.

show abstract

Section: Discussionmentioning

confidence: 99%

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

Duberg

Blach

Falconer

et al. 2014

Scandinavian Journal of Gastroenterology

View full text Add to dashboard Cite

show abstract

“…As much as 70% of otherwise eligible patients are not eligible to begin treatment due to contraindications [4,5] . A leading contraindication has been depression, since a leading side effect is the depression that may emerge or be exacerbated by interferonalpha.…”

Section: Introductionmentioning

confidence: 99%

Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

Rowan¹

2015

WJH

View full text Add to dashboard Cite

sofosbuvir regimen and the ombitasvir/paritaprevir/ ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpharelated depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. Allpill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed. Author contributions: Rowan PJ conceived the study plan, identified data sources, analyzed data, drafted the manuscript, and approved the final version; Bhulani N sought and identified relevant data for analysis per plan, contributed to analysis of data, contributed to drafting the manuscript, and approved the final version. Conflict-of-interest statement:The authors have no conflicts of interest. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments thus far seem to have short treatment timelines and relatively benign side effect profiles. Depression has not emerged as a side effect of these treatments. With efficacious regimens that include no interferon-alpha and no ribavirin, there may no longer be a need for strong psychosocial assessment and monitoring built into the routine of HCV treatment. Good history-taking, strong pharmaceutical review, and reliable consultative relationships should be adequate for meeting psychosocial needs in HCV treatment.Rowan PJ, Bhulani N. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments. World

show abstract

“…However, the efficacy of IFN-␣/ RBV varies according to both viral and host genotype, specifically with respect to polymorphisms in IL28B (5)(6)(7), and is associated with a significant burden of treatment-limiting adverse events (AEs), which result in a high rate of on-treatment dose reductions and discontinuations (8). The poor tolerability of IFN-␣/RBV also results in its contraindication in approximately 17% of HCV-infected patients (9). For the more treatment-refractory genotype 1 infections that predominate in Europe, Japan, and the United States, a newer standard of care has emerged that combines one of the recently approved HCV NS3 protease inhibitors telaprevir and boceprevir with IFN-␣/RBV for part of the overall treatment (10).…”

mentioning

confidence: 99%

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

Sims

Lemm

Eley

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

f BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC 50 ], 3 nM) and 1b (EC 50 , 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of Ϸ2.5 log 10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC 90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log 10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once-or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.)

show abstract

Absolute and relative contraindications to pegylated‐interferon or ribavirin in the US general patient population with chronic hepatitis C: results from a US database of over 45 000 HCV‐infected, evaluated patients

Abstract: SUMMARY Background

Cited by 44 publications

References 20 publications

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

Contact Info

Product

Resources

About