Additional Cost Burden on the Use of Newly Emerged DAA for Therapy
Although data from clinical trials on the use of DAA for patient management have been encouraging, its use in routine clinical practice would be highly dependent on the additional cost involved without compromising on the SVR rate. An economic analysis assessing the average cost estimates involving PI-based regimens (and compensating for treatment of adverse events suffered) revealed that PI-based therapies were cost-effective in comparison to the recommended SOC therapy (Camma, 2012). The total average cost of BOC-RGT in comparison to standard duration with BOC was found to be £22,850 vs £34,680 and £25,060 vs £34,350 for treatment-naïve and treatment-experienced patients, respectively. Similarly, the total average cost of response-guided therapy with telaprevir vs standard duration telaprevir was found to be £29,930 vs £32,530, and £31,880 vs £31,680 for treatment-naïve and treatment-experienced patients, respectively (Camma, 2012).
Duration of DAA-Based Treatment Regimen
Data from DAA-based clinical trials have revealed that >90% of patients with favorable CC-genotype (rs12979860) effectively achieved SVR and were eligible for a 24-week therapy (Jacobson, 2011b); while patients with non-CC genotypes and especially non-responders were reported to have lower SVR rates similar to those being treated with SOC therapy (Jacobson, 2011a). Hence, there seems to be a need for designing better effective treatment regimens or design dual/triple/quadruple-DAA based regimens to achieve higher SVR rates, which in turn would be associated to severe adverse events and increased risk of resistance to PI.
Lead-in SOC Therapy
The clinical relevance of lead-in therapy of SOC regimen would be more significant in patients with non-CC genotype (rs12979860); wherein patients achieving SVR would continue on non-DAA based regimen; while those not achieving SVR could be initiated on an expensive treatment regimen with DAA.
Conclusion
The changing landscape for anti-HCV therapy was marked by the introduction of pharmacogenomic-based predictive therapy (IL28B genotyping) and clinical use of DAAs (boceprevir and telaprevir). Reports from recent clinical trials have proven synergic use of IL28B genotypic results with DAA-based therapy to design personalized treatment regimens and achieve higher SVR rates. Also, a large proportion of previously treated pegIFN/RBV non-responders and relapsers can now be effectively treated with DAA-based treatment regimens thereby increasing SVR rates. But with ongoing evaluation of second-generation DAAs, the future of pharmacogenomic-based therapy in clinical practice remains uncertain.
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