Faculty Bibliography

BACKGROUND AND AIMS: African American ethnicity is a well-described negative predictor of treatment outcome for chronic hepatitis C (CHC); however, less is known about the influence of Hispanic and Asian ethnicity. The aim of this subanalysis of the Weight-based Dosing of PegINterferon alpha-2b and Ribavirin (WIN-R) study was to assess the impact of Asian (n=118), Hispanic (n=289), and white (n=3919) ethnicity on CHC treatment outcomes. METHODS: WIN-R was an investigator-initiated trial in which patients with CHC received pegylated interferon alpha-2b (1.5 mug/kg/wk) plus a fixed ribavirin dose (800 mg/d) or a weight-based ribavirin dose (800 to 1400 mg/d) for 24 or 48 weeks. RESULTS: Sustained virologic response was higher in Asian patients than in white patients (56% vs 46%, P=0.041), and higher in Asian and white patients than in Hispanic patients (56% vs 35%, P=0.0001; and 46% vs 35%, P=0.0002, respectively). In genotype 1 patients, sustained virologic response was higher in white and Asian patients than in Hispanic patients (36% and 45% vs 25%, P<0.001 for both comparisons); however, in genotype 2/3 patients, there were no significant differences among ethnic groups. Psychiatric adverse events were less common and anemia was more common in Asians than in white or Hispanic patients. Ribavirin dose reductions were less frequent in Hispanic patients than in white patients, whereas pegylated interferonalpha-2b dose reductions were more common in white patients than Hispanic patients. CONCLUSION: These observations highlight the importance of ethnicity as an integral component of the tailored treatment approach to CHC.

For a decade, standard therapy for patients with genotype 1 chronic HCV (HCV G1) consisted of pegylated interferon (Peg-IFN) alfa-2a or Peg-IFN alfa-2b, combined with ribavirin. Despite the improved efficacy of this therapy over others, the overall sustained virologic response rate in patients with HCV G1 was still low. This article discusses phase I, II, and III trials examining telaprevir's role in treating patients with HCV. We have now entered an era of combination therapy utilizing direct acting anti-virals, the start of which was marked by the FDA approval of HCV protease inhibitors.

PURPOSE: To inform nurse practitioners (NPs) of the vital role they play in recognizing patients who may have hepatitis C. DATA SOURCES: Selected review of scientific literature. CONCLUSIONS: NPs involved in the management of patients with chronic hepatitis C are well positioned to provide supportive care and contribute to the development of effective treatment strategies that maximize the opportunity for successful treatment outcomes. Although peginterferon alfa plus ribavirin therapy is associated with a well-described series of side effects, effective measures are available for the management of these events that permit the continuation of treatment and enhance the likelihood of attaining sustained virologic response. NPs can play a pivotal role in ensuring that these measures are in place in a preemptive manner. For example, growth factor supplementation represents an alternative to dose reduction or treatment discontinuation in selected patients with neutropenia or anemia and may help to improve treatment adherence. IMPLICATIONS FOR PRACTICE: Hepatitis C is a widespread problem; approximately 3% of the global population is chronically infected with the virus. Awareness of risk factors for hepatitis C will help the NP to recognize at-risk patients, who should then be screened for the virus and referred for treatment based on specific criteria.

BACKGROUND: In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. METHODS: In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). RESULTS: Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. CONCLUSIONS: Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.).