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

Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

BACKGROUND: The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. METHODS: PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). RESULTS: SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. CONCLUSION: The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.F. Hoffmann-La Roche Ltd., Basel, Switzerlan

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

Anti-HDV-IgM as a marker of disease activity in hepatitis delta

[Abstract Not Available

ANTI-HDV-IgM AS A MARKER OF DISEASE ACTIVITY IN HEPATITIS DELTA

International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) -- APR 24-28, 2013 -- Amsterdam, NETHERLANDS[Abstract Not Available]European Assoc Study Liver (EASL

PROLONGED THERAPY OF HEPATITIS DELTA FOR 96 WEEKS WITH PEGYLATED-INTERFERON-?-2a PLUS TENOFOVIR OR PLACEBO DOES NOT PREVENT HDV RNA RELAPSE AFTER TREATMENT: THE HIDIT-2 STUDY

49th Annual International Liver Congress of the European-Association-for-the-Study-of-the-Liver -- APR 09-13, 2014 -- London, ENGLAND[Abstract Not Available]European Assoc Study Live

Biomarker analyses from the phase III placebo-controlled SATURN study of maintenance erlotinib following first-line chemotherapy for advanced NSCLC

8020 Background: The SATURN (BO18192) study investigated whether erlotinib maintenance therapy improved PFS in patients (pts) with advanced NSCLC who had obtained clinical benefit from 1st-line chemotherapy. This study included a prospective analysis of the prognostic/predictive value of several molecular markers. Methods: 889 pts with advanced NSCLC whose disease had not progressed following 4 cycles of 1st-line platinum-doublet chemotherapy were randomized to erlotinib 150 mg/day or placebo. Mandatory tumor specimens were collected at baseline and tested for EGFR protein expression using immunohistochemistry (IHC), EGFR gene copy number using fluorescent in-situ hybridization (FISH), and EGFR and KRAS somatic mutations using DNA sequencing. Pts were stratified according to EGFR IHC status (any membranous staining in ≥10% tumor cells used as cut-off); the co-primary endpoint was PFS in EGFR IHC+ pts. Baseline whole blood samples were obtained for genotyping of EGFR (intron 1 CA-repeat polymorphisms). Results: In the overall population, erlotinib significantly prolonged PFS vs placebo (HR 0.71, p&lt;.0001; primary endpoint). The co-primary endpoint was also met, with erlotinib significantly improving PFS in the EGFR IHC+ group (HR 0.69, p&lt;.0001). Many tumor samples were assessable for molecular marker status (see table). Biomarker data suggest that patients derived a PFS benefit with erlotinib irrespective of EGFR FISH or EGFR intron 1 CA-repeat status. The magnitude of benefit with erlotinib was similar in both KRAS-mutant and KRAS wild-type pts. Conclusions: This is the largest biomarker analysis performed for erlotinib in a randomized, placebo-controlled setting, and answers key scientific questions regarding the prognostic and predictive value of potential biomarkers of efficacy. Full data will be presented. [Table: see text] [Table: see text] </jats:p