Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a.

BACKGROUND/AIMS: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). METHOD: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 microg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. RESULTS: Differences (HBV vs HCV) were observed in the incidence of AEs (88-89 vs 96-100%), serious AEs (4-5 vs 7-16%) and treatment withdrawals (6-8 vs 17-33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. CONCLUSIONS: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression.

Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C.

INTRODUCTION: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon alpha-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon alpha-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon alpha-2a plus ribavirin is worth the incremental cost. METHODS: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon alpha-2a plus ribavirin or interferon alpha-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. RESULTS: In patients infected with HCV genotype 1, peginterferon alpha-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon alpha-2b and ribavirin. The incremental cost per LY and QALY gained was euro9433 and euro10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon alpha-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon alpha-2b plus ribavirin. The incremental cost per LY and QALY gained was euro3261 and euro3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was euro6811 per LY gained and euro7865 per QALY gained. CONCLUSION: Our model suggests that peginterferon alpha-2a plus ribavirin is cost effective compared with conventional interferon alpha-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.

Peginterferon alpha-2a (40kD) [Pegasys] improves HR-QOL outcomes compared with unmodified interferon alpha-2a [Roferon-A]: in patients with chronic hepatitis C.

BACKGROUND: Use of unmodified interferon alpha-2a in chronic hepatitis C is associated with impaired health-related quality of life during therapy. Treatment with peginterferon alpha-2a (40kD) provides an improved sustained response over unmodified interferon alpha-2a. OBJECTIVES: To compare health-related quality of life during treatment for patients receiving peginterferon alpha-2a (40kD) [Pegasys] versus unmodified interferon alpha-2a [Roferon]. DESIGN: A randomised, international, multicentre, open-label, parallel group study. SETTING: 36 centres worldwide. PATIENTS: Interferon-naïve patients (n = 531) with chronic hepatitis C. INTERVENTIONS: Peginterferon alpha-2a (40kD) 180 mirog once a week (n = 267) for 48 weeks or unmodified interferon alpha-2a 6 million IU three times a week for 12 weeks followed by 36 weeks of 3 million IU three times a week (n = 264). MEASUREMENTS: Fatigue Severity Scale and 36-item Short-Form Health Survey (SF-36). RESULTS: At weeks 2 and 12, differences favouring peginterferon alpha-2a (40kD) were seen on seven of eight domains and both summary scores of the SF-36 (p < 0.05 to p < 0.01). At weeks 2, 12 and 24, patients receiving peginterferon alpha-2a (40kD) had less disabling fatigue (p < 0.01) than those receiving unmodified interferon alpha-2a. CONCLUSION: Treatment with peginterferon alpha-2a (40kD) is associated with less disabling fatigue and less impairment in patient functioning and well-being during treatment than unmodified interferon alpha-2a. In addition to safety and efficacy, the impact on health-related quality of life may be an important consideration for physicians when selecting an optimal treatment regimen.

Treatment of chronic hepatitis C patients with persistently normal alanine aminotransferase levels with the combination of peginterferon alpha-2a (40 kDa) plus ribavirin: impact on health-related quality of life.

BACKGROUND: Peginterferon alpha-2a (40 kDa) plus ribavirin is equally effective in chronic hepatitis C patients with normal or elevated alanine aminotransferase (ALT) values. This analysis, in patients with normal ALT levels, compared health-related quality of life (HRQoL) measurements between untreated control patients and treated patients grouped by virological response. HRQoL in the present population was also compared with HRQoL in patients with elevated ALT levels, observed in a previous study. METHODS: A total of 491 patients with persistently normal ALT levels were randomized to peginterferon alpha-2a (40 kDa)/ribavirin for 24 (group A) or 48 weeks (group B) or no treatment for 72 weeks (group C). Quality of life was assessed with valid instruments (self-administered Short Form (SF)-36 Health Survey and Fatigue Severity Scale). RESULTS: In groups A and B, patients with sustained virological responses after combination therapy had significantly better quality of life and less fatigue than patients without sustained responses. Differences were significant for five SF-36 domains, the SF-36 Physical Component score and both Fatigue Severity Scale scores. Viral clearance was not observed in any untreated patients (group C). Comparison with data from elevated ALT patients revealed little difference in baseline quality of life, although normal ALT patients had significantly higher scores related to mental health than elevated ALT patients. CONCLUSIONS: Eradication of HCV with peginterferon alpha-2a (40 kDa) plus ribavirin is associated with better quality of life and less fatigue in normal ALT patients. These patient benefits, coupled with the high probability of eradicating HCV, should be considered in making decisions about treating this population.

The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C.

BACKGROUND/AIMS: Peginterferon alfa-2a plus ribavirin improves sustained virological responses compared with interferon alfa-2b and ribavirin, or peginterferon alfa-2a alone in chronic hepatitis C. We examined the impact of these treatments on health related quality of life (HRQOL). METHODS: Patients (n=1121) were randomized to peginterferon alfa-2a weekly plus ribavirin or placebo, or interferon alfa-2b thrice weekly plus ribavirin. HRQOL was assessed with the SF-36 Health Survey and Fatigue Severity Scale (FSS). RESULTS: Patients receiving peginterferon alfa-2a plus ribavirin reported better HRQOL than those receiving interferon alfa-2b plus ribavirin. These differences were statistically significant for three SF-36 domains and both FSS scores (p<=0.05). Patients receiving peginterferon alfa-2a plus placebo had the least impairment; adding ribavirin significantly decreased five domains of the SF-36 and both FSS scores. Sustained virological response was associated with improvement at follow-up on all SF-36 and FSS scores. CONCLUSIONS: The effects of combination therapy on HRQOL and fatigue are less with peginterferon alfa-2a plus ribavirin than interferon alfa-2b plus ribavirin. Each medication in combination therapy with interferon and ribavirin, affects patients' quality of life differently. Understanding the relationship of specific therapeutic options to HRQOL may help physicians minimize the impact of therapy on HRQOL.