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 peginterferon alfa-2a/ribavirin

A Randomized controlled trial of amantadine plus interferon-alpha2a vs. interferon-alpha alone in naive patients with chronic hepatitis C randomized according to the early virological response to interferon-alpha2a monotherapy

Background: An early virological response to interferon-α treatment is a strong predictor of sustained response, but it has never been exploited to stratify patients in clinical trials. Aim: To evaluate the efficacy of amantadine plus interferon-α compared with interferon alone in naive patients with chronic hepatitis C who were randomized on the basis of the early virological response to interferon-α. Methods: One hundred and eighty-one patients received recombinant interferon-α (3 MU three times weekly) for 2 months and 164 were evaluated for early (i.e. month 2) virological response. Hepatitis C virus (HCV) RNA-negative patients (n = 66) were randomized to receive 3 MU of interferon-α three times weekly, with or without amantadine (200 mg/day); HCV RNA-positive patients (n = 98) were randomized to receive 6 MU of interferon-α three times weekly, with or without amantadine (200 mg/day). HCV RNA-positive patients at 6 months discontinued treatment, and all others completed 12 months. Results: At month 6, HCV RNA-negative patients made up 54.2% of the interferon + amantadine group and 42.0% of the monotherapy group (P = 0.07). At month 12, HCV RNA-negative patients made up 38.5% of the interferon + amantadine group and 28.4% of the monotherapy group (N.S.). The sustained virological response rates were 21.6% and 20.9%, respectively (N.S.). Conclusion: The addition of amantadine does not enhance the sustained virological response to interferon-α in naive patients with chronic hepatitis C; however, an additive effect of amantadine occurs in the first 6 months, mainly in patients without an early response to monotherapy. Early response to interferon-α is a strong predictor of sustained virological response

Pro-Inflammatory Genetic Profiles in Subjects with Peripheral Arterial Occlusive Disease and Critical Limb Ischemia

OBJECTIVES: Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. DESIGN, SUBJECTS, AND METHODS: A genetic association study including 157 PAOD patients and 206 controls. The following gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6) -174 G/C, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chemoattractant protein (MCP-1) 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3 -1171 5A/6A, and MMP-9-1563 C/T. RESULTS: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1, and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. CONCLUSIONS: Proinflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for presence and severity of atherosclerotic disorder

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 &lt;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 &lt;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 &lt;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. \ua9 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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 peginter-feron alfa-2a/ribavirin