Consensus Interferon: Tailored Therapy and the Impact of Adherence

Abstract

A successful course of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection is durable and can result in significant long-term benefit; however, many patients who undergo combination therapy with pegylated interferon alfa (PegIFN) and ribavirin (RBV) ultimately fail and develop persistent viremia. Our ability to achieve a sustained virologic response (SVR) is especially limited in patients with genotype 1 infection. Additional factors that characterize the most challenging subgroups of treatment candidates include those with advanced fibrosis or cirrhosis, fatty liver disease, increased age, obesity, and African American ethnicity [1–6]. Based on several large prospective randomized clinical trials, the rates of SVR associated with genotype 1 infection have ranged from 41 to 52% [1–3, 5]. These studies have demonstrated further reductions in SVR to as low as 35% in genotype 1 patients with a high viral load [2, 3, 5]. In an effort to increase the potential of achieving an SVR while optimizing adherence to therapy, various strategies have emerged with an emphasis towards an individualized approach. Although some data are conflicting, proposed strategies have included a shortened duration of treatment in subsets of patients with favorable characteristics, including low baseline serum HCV RNA levels and rapid virologic response (RVR) during therapy [7–17]. Alternatively, a key strategy applicable to patients with genotype 1 infection is the extension of treatment duration based on the timing of viral clearance, in which patients with a slow virologic response may receive up to 72 weeks of therapy [17–22]. Other strategies have involved the use of alternative and potentially more potent forms of interferon-based therapy. Although higher doses of PegIFN and RBV may result in more rapid viral suppression and an increase in SVR, this appears to occur at the cost of decreased tolerability as demonstrated in a recent prospective study [23]. Consensus interferon (CIFN) has emerged as a viable treatment option in both naive and previously treated patients with chronic HCV, particularly in those with difficult-to-treat characteristics. CIFN is a synthetic type I interferon protein that comprises a consensus sequence of the most common amino acids found in naturally occurring alpha interferon subtypes. Initial in vitro studies suggested that CIFN has superior antiviral efficacy in comparison with interferon alfa (IFN) [24], while prospective clinical data have reported a significant increase in SVR for genotype 1 patients with high viral load treated with CIFN versus standard IFN [25, 26]. Although comparative data are limited, one study suggests that CIFN may be as effective as PegIFN when used in combination with RBV for the treatment of genotype 1 patients [27]. A long-acting form of CIFN is not available; however, daily dosing may further enhance viral suppression [28] and has been shown to be an effective dosing strategy in a large prospective clinical trial of patients who failed prior PegIFN and RBV therapy [29]. In this issue of Digestive Diseases and Sciences, Ho and colleagues present their experience with a tailored approach to therapy in a cohort of treatment-naive genotype 1 patients with difficult-to-treat characteristics, utilizing strategies including extended treatment duration and the use of high-dose daily CIFN (15 mcg) in combination S. A. Gonzalez (&) Division of General and Transplant Hepatology, Baylor Regional Transplant Institute, Baylor All Saints Medical Center, 1250 8th Avenue, Suite 515, Fort Worth, TX 76104, USA e-mail: stevan.gonzalez@baylorhealth.edu