However, not all patients may benefit from these new types of IFNs. In particular, it seems unlikely that patients with strong contraindications to the current IFNs will be eligible for treatment with newer formulations, even if the AEs profiles of the new IFNs are milder. Viagra tablets
Interferon alfacon or consensus interferon (CIFN) (Infergen®, Three Rivers Pharmaceuticals) is a recombinant, bio-engineered interferon, consisting of the most frequently observed amino acid in each corresponding position in the natural alfa IFN. It shares an 89%, 30% and 60% homology with IFN alfa, IFN beta and IFN omega, respectively. The CIFN molecule binds to the IFN-alfa receptor with higher affinity than all other known IFN alfa molecules (including the natural subtypes, the variants or recombinants). In vitro it appears to be approximately 5 to 20- fold more active than PegIFN alfa-2a and alfa-2b (Gonzalez 2009). Data derived from clinical trials support the use of CIFN for treatment-naive patients, particularly those with high VL or genotype 1 infection (Sjogren 2005), as well as in the retreatment of relapsers and nonresponders (Leevy 2008). Clinical trials suggested a dose-dependent rate of viral clearance, however the maximum tolerated dose of daily CIFN in difficult-to-treat patients is up to 15 μg/day (Bacon 2009). Administration of an induction dose (up to 18μg/day) or of a higher dose (24μg/day), did not translate to better rates of SVRs and was associated with more serious AEs and more discontinuations (Meyer 2010).
CIFN is approved as monotherapy for CHC in adults with compensated liver disease, and, from 2010, for retreatment of CHC, in combination with RBV, being especially effective for interferon-sensitive patients with lower baseline fibrosis scores.
IFN lambda (IFN-λ) is a type III interferon (comprising of IL28A, IL28B and IL29), which has previously demonstrated strong antiviral activity and good tolerability. IFN-λ mediates antiviral activity through a different signaling pathway than type I interferons (such as IFN alfa), having a complex binding mainly through the IL28 receptor, which is present only on plasmacytoid dendritic cells, peripheral B cell, hepatocytes and epithelial cells. This restricted distribution compared to that of IFN-alfa receptor offers the potential for more targeted hepatic delivery, as well as for a better tolerability and safety profile than the conventional interferons in terms of bone marrow suppression (Sommereyns 2008). IFN-λ can enhance the subsaturating levels of IFN-ɑ and increase its antiviral efficacy. As a result, the combination of IFNλ and IFN-ɑ may provide additive therapeutic effects through the complementary roles of the two types of cytokines (Pagliaccetti 2008). IFN-λ may be used to target specific cell responses and to avoid the AEs of IFN-ɑs. Interferon lambda has been pegylated (Zymogenetics/Bristol-Myers Squibb); its administration in treatment-naive patients chronically infected with HCV genotypes 1/2/3/4 resulted in higher rates of RVR and EVR, which extended across all IL28B host genotypes, and was associated with fewer hematologic toxicities, flu-like and musculoskeletal symptoms compared with PegIFNɑ-2a (Zeuzem 2011). IFN lambda might prove to be increasingly important for the treatment of CHC, due to the recent findings on the impact of host genetics in the response to therapy (Tanaka 2010).