Reply

Abstract

According to the recently released American Association for the Study of Liver Diseases (AASLD) guidelines for the treatment of hepatitis C virus (HCV) genotype 1 chronic infection, 1 in treatment-naïve subjects the association of boceprevir or telaprevir with peginterferon-alpha and ribavirin is strongly recommended as the optimal therapy. In patients treated with boceprevir, peginterferon, and ribavirin, a response-guided treatment schedule was established at week 8, through the assessment of HCV RNA level, making feasible a shortened duration of treatment (i.e., 28 weeks) in the case of undetectable viral replication. In this regard, we believe that the choice of 8 weeks for the definition of treatment duration needs some comment. The phase 2 and 3 clinical trials with boceprevir 2,3 featured the use of peginterferon-ribavirin for 4 weeks (the lead-in period) before boceprevir was added. The reasons for starting with a lead-in phase would be to lower HCV-RNA before exposure to a protease inhibitor in order to reduce the risk of resistance and viral breakthrough. 2 However, in the studies mentioned the achievement of virologic response after the lead-in therapy (4 weeks) was shown to be highly effective for the prediction of sustained virologic response (SVR; HCV-RNA undetectability leading to SVR in a percentage of patients between 89% and 100%, independently from the treatment arm). 2,3 Indeed, Poordad et al. 3 stated that in patients with undetectable HCV RNA levels after the lead-in period, boceprevir administration would not result in a higher rate of SVR than that obtained with the use of standard therapy. Therefore, the lead-in period as well as interleukin (IL)-28B genotype assessment might be used to better define the eligible patients for peginterferon introduction, thus avoiding their possible overuse with additional costs and side effects. In our opinion, it seems to be reasonable to reconsider the assessment of HCV-RNA at week 4 (end of lead-in) in the response-guided treatment guidelines of naïve genotype-1-infected patients.

A Population Approach to Disease Management: Hepatitis C Direct-Acting Antiviral Use in a Large Health Care System

“…Using CCR:HCV laboratory and prescription data from all 130 VHA facilities, we produced reports of facility, regional (the VA system is divided into 21 regions, or veterans integrated service networks), and national level populations identifying the number of veterans with HCV genotype 1 infection who were in need of treatment as determined by a detectable HCV viral load, as well as those who appeared to be eligible candidates based on the indication for therapy and expected contraindications. 8 Using pharmacy records to track historical use of peginterferon plus ribavirin, we constructed models of drug uptake using historical caseloads for VA HCV treatment and projected rates of new treatment caseloads over time. The models assumed the following: the numbers of veterans with HCV in care would remain stable; only genotype 1 HCVinfected patients would be eligible for treatment; both treatment naïve and experienced patients would be eligible; patients with contraindications to peginterferon or ribavirin (based on VA comorbidity data in HCV-infected veterans) would remain ineligible for treatment; and yearly HCV treatment rates would range from 5% to 25% of those eligible based on historical VA treatment rates.…”

“…[4][5][6][7] Despite advances in efficacy, evidence suggested that boceprevir-or telaprevir-based regimens would be more difficult to manage because of complex treatment algorithms, higher pill burden, complicated drug interactions, and adverse effects, particularly anemia. [8][9] Safety and effectiveness data in real-world populations, such as veterans, with comorbidities or relative contraindications upon which to make formulary decisions did not exist. Demand for these agents was great given the landmark changes in response, yet the baseline characteristics of the clinical trial populations in whom these agents were evaluated were substantially different from those of the VA HCV-infected population.…”

Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin

“…The addition of PIs to the previous standard of care, Peg-interferon (PegIFN) and ribavirin (RBV), has boosted the sustained virologic response (SVR) to approximately 75% in treatmentnaïve patients [1] and [2]. Echoing these results, scientific communities [3] and [4] and governmental health care organizations [5] recommended triple therapies with PegIFN, RBV, and PIs as the new standard of care for genotype 1 untreated and previously treated patients. The therapeutic advances with triple therapies came at the expenses of increased adverse effects, significant drug-drug interactions, and induction of viral mutations.…”

A Review of Hepatitis C in the General Population in Pakistan

“…Previously, the only available therapy was interferon for 6 to 24 weeks (3 million international units) or the same intravenous dose of interferon for 4 to 7 weeks (105). Since 2001, pegylated interferon α with ribavirin has shown favorable results against genotype 2 and 3 (106).…”