Real-world studies show 8-week sofosbuvir/ledipasvir course just as effective as 12-week course for genotype 1 patients without cirrhosis

Keith Alcorn
Published:
02 December 2016

An 8-week course of treatment with sofosbuvir/ledipasvir is just as effective as a 12-week course of treatment in people without cirrhosis, including those with HIV/hepatitis C virus (HCV) co-infection, and could significantly reduce the cost of treatment if it was prescribed more widely, several large real-life cohort studies presented at last month’s 2016 AASLD Liver Meeting in Boston show.

The US Food and Drug Administration (FDA) recommends that an 8-week course of treatment with sofosbuvir/ledipasvir can be considered for previously untreated people with genotype 1 infection who do not have cirrhosis or a pre-treatment HCV viral load above 6 million IU/ml. This recommendation was based on post-hoc analysis of the phase III ION-3 trial but has not been confirmed in real-world clinical practice.

Furthermore, some liver specialists are sceptical about the effectiveness of an 8-week course of sofosbuvir/ledipasvir in people with HIV/HCV co-infection who do not have cirrhosis. Two phase III studies, PHOTON-1 and 2, tested a 12-week course of treatment in people with co-infection, confirming a high level of efficacy of the combination in people with co-infection. The ION-3 study of an 8-week course of treatment excluded people with co-infection, leading to an absence of evidence on the question. Cohort data have also been lacking, with the exception of data from the German GECCO multicentre cohort, which showed a very high cure rate (98.5%) in a small cohort.

Glossary

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

Three studies presented at The Liver Meeting provided reassuring evidence on the use of an 8-week treatment course in real-life, in people with high viral load and in people with co-infection.

8-week regimen pooled analysis

The largest study was designed to determine the effectiveness of an 8-week regimen in people who met the FDA criteria, and to identify predictors of relapse.

The analysis pooled data from four cohorts: Burman’s Pharmacy (n = 307), Kaiser Permanente Southern California (n = 203), the Institute for Interdisciplinary Medicine (Hamburg) (n = 126) and HCV Trio (n = 232). The HCV Trio network includes academic and community-based clinics throughout the United States.

The analysis excluded anyone treated with ribavirin and those lacking recent fibrosis staging information, as well as those treated post-transplantation. The analysis identified 868 people who received an 8-week course of sofosbuvir/ledipasvir, of which 798 people met the FDA eligibility criteria. Sixty-one individuals were excluded from the per-protocol analysis on the grounds that they had baseline viral loads above 6 million IU/ml.

The cohort was evenly comprised of men and women, 62.7% white, 25% African-American and 10% Hispanic. Approximately two-thirds of people had genotype 1a infection and the vast majority had less advanced fibrosis (F0-F2) (82.7%).

The per-protocol analysis showed that 98.5% of people treated according to FDA guidance achieved sustained virological response (SVR12). Sub-group analysis showed that at least 95% of people achieved SVR12 in all sub-groups, and logistic regression analysis found no variables associated with relapse.

All 61 individuals with baseline viral load above 6 million IU/ml achieved SVR12.

A separate systematic review by the same group identified six additional studies reporting comparative outcomes in people treated with sofosbuvir/ledipasvir for 8 or 12 weeks. The pooled population comprised 5637 people and per-protocol SVR12 rates were 95.8% in those treated for 8 weeks and 97.2% in those treated for 12 weeks, a non-significant difference. There was no significant difference in the risk of viral relapse.

8-week regimen in German cohort

An analysis of the Deutsches Hepatitis-C Register also found that people treated for 8 weeks enjoy comparable outcomes to those of people treated for 12 weeks. The Deutsches Hepatitis-C Register is a prospective register of hepatitis C treatment outcomes in people treated with direct-acting antivirals.

Of 8090 people who started treatment between 1 February 2014 and 30 June 2016, 2543 people with genotype 1 infection had completed an 8 or 12-week course of sofosbuvir/ledipasvir treatment according to protocol and had SVR follow up data. A total of 976 people received an 8-week regimen and 1509 people received a 12-week regimen. Those who received the 12-week regimen were an average of four years older and had higher liver stiffness measurements, but because this analysis excluded people who received ribavirin, the proportion of the 12-week group who had cirrhosis was low (12%). Of the 12-week group, 58.7% had previous treatment experience.

The analysis showed that 98% of each group achieved SVR12.

The cohort included 278 people with HIV/HCV co-infection: 9.3% of the 8-week group and 12.4% of the 12-week group. Ninety-six per cent of the 8-week co-infected group and 98% of the 12-week co-infected group achieved SVR12.

Regression analysis showed that cirrhosis was the only risk factor for viral relapse in those who received an 8-week course of treatment (2.4% of the 8-week group had cirrhosis). Viral load above 6 million IU/ml did not predict viral relapse, nor did previous treatment experience. The investigators concluded that a large proportion of the cohort was over-treated with a 12-week course of sofosbuvir/ledipasvir.

8-week regimen in people with HIV/HCV co-infection

An open-label phase IIIb study in Russia and Estonia also found no substantial difference in outcome between previously untreated people with HIV/HCV co-infection or monoinfection treated with sofosbuvir/ledipasvir for 12 weeks.

The study population comprised 67 people with monoinfection and 59 people with co-infection, all with genotype 1 infection. Study participants had high viral load (a mean of 5.9 million IU.ml in the monoinfection group and 6.1 million in the co-infection group).

All participants (100%) in the monoinfection arm and 57 of 59 people (97%) in the co-infection arm achieved SVR12. Both cases of virologic failure occurred in people with genotype 1a infection.

References

Buggisch P et al. 8 weeks treatment under real life conditions with ledipasvir/sofosbuvir in HIV co infected treatment-naïve HCV genotype 1 infected patients with similar results to mono-infected HCV patients: data from the German Hepatitis-C Registry (DHC-R). Hepatology Special Issue, The 67th Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting, abstract 883, Boston, 2016.

Isakov V et al. Ledipasvir/sofosbuvir for 8 weeks results in high SVR rates in treatment-naïve patients with chronic HCV infection and HIV/HCV coinfection. Hepatology Special Issue, The 67th Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting, abstract 2030, Boston, 2016.

Sundaram V et al. Eight weeks treatment duration with ledipasvir/sofosbuvir (LDV/SOF) is effective for appropriately selected patients with genotype 1 hepatitis C virus (HCV) infection: an analysis of multiple real world cohorts totalling >6,500 patients. Hepatology Special Issue, The 67th Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting, abstract LB-16, Boston, 2016.