Effectiveness of 8- or 12-Weeks of Ledipasvir and Sofosbuvir in Real-World Treatment-Naïve, Genotype 1 Hepatitis C Infected Patients

M. P. Curry; E. B. Tapper; B. Bacon; D. Dieterich; S. L. Flamm; L. Guest; K. V. Kowdley; Y. Lee; S. Milligan; N. Tsai; Z. Younossi; N. H. Afdhal

Disclosures

Aliment Pharmacol Ther. 2017;46(5):540-548. 

In This Article

Abstract and Introduction

Abstract

Background: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks.

Aim: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting.

Methods: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients.

Results: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables.

Conclusions: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.

Introduction

Background. There is an estimated 80–185 million people infected with Hepatitis C virus (HCV) worldwide.[1,2] Despite the reduction in new infections in recent years, morbidity and mortality related to chronic infection are likely to increase.[3] Since 2011, there has been the development of several new regimens of direct acting anti-virals associated with significant improvements in efficacy and tolerability in treatment of HCV. Eradication of HCV is associated with decreased overall morbidity and mortality as well as increased quality of life and reduced healthcare utilisation.[4,5] Based on the prevalence of infection and availability of highly effective direct acting antivirals, treatment is now recommended for all patients with chronic HCV infection.

However, due to the high wholesale cost of direct acting anti-viral treatment regimens, one of the commonly cited barriers to treatment is the cost of therapy.[6] Despite this high cost, treatment of naïve genotype 1 HCV patients is considered to be a cost-effective strategy when compared with other accepted medical practices.[7–9] Ledipasvir and sofosbuvir fixed dose combination (LDV/SOF) is approved by the Food and Drug Administration for the treatment of genotype 1 HCV infection in treatment-naïve patients with and without cirrhosis based on two registration trials called ION-1 and ION-3.[10,11] The ION-3 study of treatment-naïve noncirrhotic patients investigated LDV/SOF with or without ribavirin for 8 or 12 weeks and LDV/SOF for 12 weeks. Treatment-naïve noncirrhotic patients infected with genotype 1 who received LDV/SOF for 8 weeks achieved an SVR rate of 94%. This SVR was not inferior to a 12-week regimen of LDV/SOF in an intent-to-treat analysis. Relapse rates were found to be higher in the cohort of patients randomised to 8 weeks of treatment regardless of ribavirin. However, in a post hoc analysis of the ribavirin-free treatment arms, patients with baseline HCV RNA levels <6 million IU/mL were found to have similarly high SVR rates and low relapse rates regardless of 8- or 12-week treatment durations. While this analysis was not controlled, the Food and Drug Administration included consideration of 8 weeks of LDV/SOF in genotype 1 treatment-naïve patients without cirrhosis who have a pre-treatment viral load of <6 million IU/mL.[12] Despite the approval of the Food and Drug Administration, the American Association for Study of Liver Disease/Infectious Diseases Society of America guidelines for the treatment of HCV state that shortening of therapy for less than 12 weeks is not recommended in African-American patients, patients with Human Immunodeficiency Virus infection and patients with known interleukin-28B polymorphism CT or TT.[13] Guidelines from the European Association for the Study of the Liver state that treatment may be shortened to 8 weeks in treatment-naïve patients without cirrhosis if their baseline HCV RNA level is below 6 million (6.8 Log) IU/mL, however, caution should be exercised especially in patients with F3 fibrosis, pending confirmation of these results in real-life studies.[14] Last, the English National Health Service guidance recommends 8 weeks of LDV/SOF for noncirrhotic treatment-naïve genotype 1 HCV infected patients regardless of HCV viral load.[15] Several heterogeneous real-world cohort studies have reported excellent SVR rates for patients treated for 8 weeks with LDV/SOF±ribavirin.[16–23]

The importance of these recommendations for the possible shortening of duration cannot be underestimated as it is likely that there is a significant population of patients who meet these criteria who could benefit from a shortened, and thus less costly, course of treatment. However, the baseline HCV viral load cut off of 6 million IU/mL has been called into question, as the post hoc analysis was underpowered and may reflect a statistical artefact.[24]

Aim. We chose to evaluate SVR rates following LDV/SOF without ribavirin for genotype 1, treatment-naïve patients in a real-world cohort of patients who have been treated for 8 or 12 weeks.

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