The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C☆
Introduction
Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. In the United States alone, nearly 4 million individuals are infected with this virus [1]. Currently, hepatitis C is responsible for an estimated 8000–10,000 deaths annually [2], and without effective intervention, that number is postulated to triple in the next 10–20 years [3]. Hepatitis C is now the leading reason for liver transplantation in the United States [4]. Patients with chronic hepatitis C also have more impaired health-related quality of life (HRQOL) than the general population [5], [6], [7], [8], [9]. In addition, soon after the onset of treatment with interferon monotherapy or interferon plus ribavirin, patients report increased incidence and severity of fatigue, pain, and mood changes that interfere with physical and emotional well-being, work productivity, and activities of daily living [5], [10], [11]. These changes in HRQOL might adversely affect adherence and result in early discontinuation of therapy. Previous research on hepatitis C therapy has shown that such declines in HRQOL increase the risk of premature treatment discontinuation [12].
In a randomized clinical trial, peginterferon alfa-2a has demonstrated increased efficacy (sustained virological response rate after completion of treatment) in monotherapy compared with conventional interferon alfa-2a [13]. Analysis of HRQOL in that trial found that patients in the peginterferon alfa-2a group reported significantly less impairment of HRQOL during therapy than those in the conventional interferon alfa-2a group [14]. The current standard of care for patients with chronic hepatitis C is combination therapy using interferon and ribavirin [15], [16], [17], [18], [19], [20]. In a recent multinational, randomized trial, combination therapy with peginterferon alfa-2a plus ribavirin demonstrated increased efficacy compared with peginterferon alfa-2a alone (56 vs. 29%, P≤0.001) and interferon alfa-2b plus ribavirin (56 vs. 44%, P≤0.001) [21]. The study also found significantly lower rates of influenza-like symptoms (fever, headache, myalgia, and rigors) with peginterferon alfa-2a plus ribavirin vs. interferon alfa-2b plus ribavirin [21]. Lower rates of these adverse events may contribute to less impairment of HRQOL during therapy with peginterferon alfa-2a plus ribavirin vs. interferon alfa-2b plus ribavirin.
The present study examined differences in HRQOL experienced by patients randomized to 48 weeks of treatment with either peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus ribavirin, or interferon alfa-2b plus ribavirin. The purpose of the study was threefold. First, to determine whether peginterferon alfa-2a plus ribavirin was associated with less impairment of HRQOL and less fatigue burden than interferon alfa-2b plus ribavirin. Second to test previous findings [5], [7], [12], [14] that successful treatment of HCV is associated with significant improvements in patient quality of life. Third, to compare the HRQOL experienced by patients in the peginterferon alfa-2a plus placebo and peginterferon alfa-2a plus ribavirin groups in order to examine the specific effects of both peginterferon alfa-2a and ribavirin when used in combination, on HRQOL.
Section snippets
Methods
This study was based on data from an international, multicenter, open-label, randomized, parallel, efficacy and safety study comparing peginterferon alfa-2a (Pegasys®, Roche) plus ribavirin (Copegus®, Roche) or placebo, or interferon alfa-2b plus ribavirin (Rebetron™, Schering-Plough Corporation, Kenilworth, NJ, USA) [21]. Peginterferon alfa-2a was administered as a once-weekly subcutaneous injection of 180 μg, while interferon alfa-2b was administered as a subcutaneous injection of 3 million
Patient demographics
A total of 1121 patients were randomized and received at least one dose of either peginterferon alfa-2a plus placebo, peginterferon alfa-2a plus ribavirin or interferon alfa-2b plus ribavirin. There were no significant differences between treatment groups for any baseline demographic or clinical characteristic (Table 1). The baseline SF-36 and FSS scores also did not significantly differ by treatment group. The mean age of the patients was 43 years; 71% were males, and the mean body mass index
Discussion
Combination therapy with interferon and ribavirin for CHC has become increasingly effective, however, patients continue to report difficulties with HRQOL during treatment. In this study combination therapy with peginterferon alfa-2a plus ribavirin was associated with better HRQOL and less burden of fatigue than interferon alfa-2b plus ribavirin across a broad spectrum of HRQOL domains. This improved HRQOL and fatigue may be due to the sustained serum levels produced by the weekly dosing
Conclusion
Previous studies in patients with chronic hepatitis C have demonstrated that interferon therapy has a negative effect on HRQOL, as measured by the SF-36 during the initial 12–24 weeks of treatment [5], [28]. Although patient functioning and well-being eventually return to pre-treatment levels at the end of therapy, the worsening HRQOL while on treatment may negatively influence compliance and ultimately contribute to an unfavorable clinical outcome [12]. When choosing optimal therapy for
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The authors declare that they received funding from Roche Pharmaceuticals to carry out the study.