Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

Marcel Nkuize,1 Thomas Serst&eacute;,1,2 Michel Buset,1 Jean-Pierre Mulkay11Department of Gastroenterology and Hepatology, Saint-Pierre University Hospital, 2Department of Gastroenterology, Pancreatology and Hepatology, H&ocirc;pital Academique Erasme, Universit&eacute; Libre de Bruxelles, Brussels, Belgium Abstract: Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-na&iuml;ve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV&ndash;hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection.Keywords: ledipasvir, liver disease, ethnicity, DAA, HI

Response of Black African patients with hepatitis C virus genotype 4 to treatment with peg-interferon and ribavirin

Aim : To compare responses to therapy of Black African (BA) and non-Black African (non- BA) patients with hepatitis C virus genotype 4 (HCV-4) residing in Belgium. Methods : In this retrospective multicenter study, 473 patients with HCV-4 were selected from databases at 7 Belgian centers ; 209 treatment-naïve patients (154 BA) had received treatment with peg-interferon (peg-IFN) plus ribavirin (RBV) and were included in the study. Results : There was a greater percentage of female patients in the BA group than in the non- BA group ; BA patients were also older, had a greater body mass index, and more frequently had abnormal glucose metabolism. The route of contamination was more frequently unknown in BA than in non-BA patients and BA patients had more HCV-4 subtypes. There were no differences in other demographic factors between the groups. Sustained viral response (SVR) and complete early viral response rates were significantly lower and relapse rates significantly higher in BA than in non-BA patients. There were no differences between groups in rates of dose modification or in drug tolerance. Conclusion : In our cohort, treatment-naïve BA patients with HCV-4 who were treated with peg-IFN and ribavirin had a much lower SVR rate than treatment-naïve non-BA patients with HCV- 4 who were treated with peg-IFN and ribavirin, and a higher relapse rate, possibly related to a weaker response to interferonbased therapy. Treatment may need to be adapted in this population

Ethnic epidemiological profiles and antiviral therapy among patients infected with hepatitis C virus genotype 4: a multicenter study from Belgium.

Background: Hepatitis C virus genotype 4 (HCV-4) is the most prevalent genotype in Central Africa. A large population of Black African individuals, among whom HCV-4 infection is widespread, resides in Belgium. Aim: To compare epidemiology, clinical characteristics and any differences in receipt of HCV therapy in two populations of HCV-4 patients residing in Belgium. Methods: This retrospective multicenter study selected 473 patients from seven hospital databases and compared them according to ethnic origin, i.e., Black African (n=331) or not (n=142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 Black African and 30 non-Black African patients. Results: Compared to other patients, the Black African patients were more likely to be female and were older, more commonly overweight, more frequently had abnormal glucose metabolism and arterial hypertension; they were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in Black African than in other patients. Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups. Conclusion: In this Belgian cohort, patients with HCV-4 infection were more frequently of Black African origin than of other origin. Infected Black African patients were more commonly female, older at diagnosis, and had more co-morbidities than other patients; they also had less advanced liver fibrosis than infected non-Black African patients and fewer had a CC genotype. The number of patients treated with antiviral therapy was similar in the two groups

Update of the Belgian Association for the Study of the Liver Guidelines for the treatment of chronic hepatitis C genotype 1 with protease inhibitors.

Journal ArticlePractice GuidelineSCOPUS: ar.jinfo:eu-repo/semantics/publishe

A multicentre, observational study on demographic and disease characteristics of patients seeking care for chronic hepatitis C in Belgium in 2016

Background and Study Aims: Direct-acting antivirals provide interferon-free treatments for chronic hepatitis C (CHC) virus infection. In Belgium, in 2016, access to these agents was limited to patients with advanced liver fibrosis stages F3 and F4. This study is the first to describe Belgium’s patient population ineligible for interferon-free treatment. Patients and Methods: This was an observational, cross-sectional, multicentre study that enrolled adult patients with CHC ineligible for interferon-free treatment. Patient data recorded at a single visit included demographic data, disease characteristics, comorbidities, co-medications, treatment status, and laboratory data. Results: Three hundred and three patients from 16 centres in Belgium were included in the statistical analysis. On average, patients were aged 53.5 years and 50.2% were women; 94.1% had health insurance and 99.0% resided in Belgium. The current hepatitis C virus (HCV) infection was the first infection for 96.0% of patients and the mean time since infection was 20.0 years. Liver fibrosis stage was F0 for 23.7%, F0/F1 or F1 for 38.3%, F1/ F2 or F2 for 25.8%, F3 for 7.1%, and F4 for 5.1% of patients; 28.4% of patients were CHC treatment-experienced. The main reason for ineligibility for interferon-free treatment was lack of reimbursement (84.8%). Other reasons included no treatment urgency or medical decision to wait (27.1%), waiting for future treatment option (8.3%), and no social insurance coverage (3.6%). Conclusions: This study provides recent data on the CHC patient population and disease characteristics in Belgium that could help medical communities and government agencies manage CHC disease burden.SCOPUS: ar.jinfo:eu-repo/semantics/publishe