Chronic HCV Therapy: Sustained Virological Response
Chronic HCV Therapy: Sustained Virological Response
The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (<150 000/μL). Among patients treated with peginterferon plus RBV in routine clinical practice, genotype, baseline viral load, age, GGT level and platelet levels all predict the likelihood of treatment success. In patients matched by baseline characteristics, treatment with peginterferon alfa-2a may be a positive predictor of SVR when compared to peginterferon alfa-2b.
Chronic infection with hepatitis C virus (HCV) is responsible for substantial morbidity and mortality worldwide. Approximately 130 million people are estimated to suffer from chronic hepatitis C at risk of long-term complications such as liver cirrhosis and hepatocellular carcinoma. Treatment with peginterferon plus ribavirin (RBV) is the current standard of care for patients with chronic hepatitis C (CHC). Data from pivotal trials demonstrated rates of sustained virological response (SVR) in 40–50% of genotype 1-infected and in about 70–80% of genotype 2-infected individuals. These study results are the basis of current treatment guidelines. Although treatment with peginterferon and RBV offers the chance of a cure, adverse events may be limiting in some patients. Well-documented adverse events of therapy include fatigue, flu-like symptoms, depression, thrombocytopenia and neutropenia. The perception of such possible adverse events may affect the patient's acceptance of the decision to start treatment, present on-treatment management challenges and may affect adherence which can in turn affect treatment outcome. For patients and physicians, the likelihood of a successful therapy is one of the most relevant factors for a decision to start or defer therapy for CHC. The ability to predict the likelihood of SVR before the start of therapy may guide treatment decisions and encourage adherence.
A number of predictive variables for treatment success have been identified in trials of peginterferon plus RBV. Data from randomized, controlled clinical trials are the basis for the development of clinical guidelines and for decisions regarding patient management. However, it is important that results of such trials are assessed in 'real-world' situation. The PRACTICE (pegylated interferons and ribavirin: analysis of chronic hepatitis C treatment in centres of excellence) study is a German nationwide retrospective observational study analysing the response to hepatitis C treatment in routine clinical practice between 2000 and 2007. This study is a retrospective data collection of patients with HCV treated under real-life conditions, who were exposed to factors, which may potentially influence outcome, which are different from the highly controlled setting of clinical trials (e.g. nonacademic clinics, more difficult to treat patients, prescribing behaviour, social and economic differences). The aim of this study was to identify predictive factors for SVR in patients with CHC included in PRACTICE treated with peginterferon plus RBV under real-life conditions when compared with those treated under clinical trial conditions. As certain characteristics are known to affect response, patients were analysed in pairs matched by a range of baseline factors (matched-pair analyses), allowing conclusions regarding predictive factors for groups of patients with identical baseline characteristics.
Abstract and Introduction
Abstract
The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (<150 000/μL). Among patients treated with peginterferon plus RBV in routine clinical practice, genotype, baseline viral load, age, GGT level and platelet levels all predict the likelihood of treatment success. In patients matched by baseline characteristics, treatment with peginterferon alfa-2a may be a positive predictor of SVR when compared to peginterferon alfa-2b.
Introduction
Chronic infection with hepatitis C virus (HCV) is responsible for substantial morbidity and mortality worldwide. Approximately 130 million people are estimated to suffer from chronic hepatitis C at risk of long-term complications such as liver cirrhosis and hepatocellular carcinoma. Treatment with peginterferon plus ribavirin (RBV) is the current standard of care for patients with chronic hepatitis C (CHC). Data from pivotal trials demonstrated rates of sustained virological response (SVR) in 40–50% of genotype 1-infected and in about 70–80% of genotype 2-infected individuals. These study results are the basis of current treatment guidelines. Although treatment with peginterferon and RBV offers the chance of a cure, adverse events may be limiting in some patients. Well-documented adverse events of therapy include fatigue, flu-like symptoms, depression, thrombocytopenia and neutropenia. The perception of such possible adverse events may affect the patient's acceptance of the decision to start treatment, present on-treatment management challenges and may affect adherence which can in turn affect treatment outcome. For patients and physicians, the likelihood of a successful therapy is one of the most relevant factors for a decision to start or defer therapy for CHC. The ability to predict the likelihood of SVR before the start of therapy may guide treatment decisions and encourage adherence.
A number of predictive variables for treatment success have been identified in trials of peginterferon plus RBV. Data from randomized, controlled clinical trials are the basis for the development of clinical guidelines and for decisions regarding patient management. However, it is important that results of such trials are assessed in 'real-world' situation. The PRACTICE (pegylated interferons and ribavirin: analysis of chronic hepatitis C treatment in centres of excellence) study is a German nationwide retrospective observational study analysing the response to hepatitis C treatment in routine clinical practice between 2000 and 2007. This study is a retrospective data collection of patients with HCV treated under real-life conditions, who were exposed to factors, which may potentially influence outcome, which are different from the highly controlled setting of clinical trials (e.g. nonacademic clinics, more difficult to treat patients, prescribing behaviour, social and economic differences). The aim of this study was to identify predictive factors for SVR in patients with CHC included in PRACTICE treated with peginterferon plus RBV under real-life conditions when compared with those treated under clinical trial conditions. As certain characteristics are known to affect response, patients were analysed in pairs matched by a range of baseline factors (matched-pair analyses), allowing conclusions regarding predictive factors for groups of patients with identical baseline characteristics.
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