AASLD 2016: Real-World Studies Show 8 Weeks of Sofosbuvir/Ledipasvir Equals 12 Weeks for Many Patients
- Category: HCV Treatment
- Published on Thursday, 15 December 2016 00:00
- Written by Keith Alcorn
An 8-week course of treatment with sofosbuvir/ledipasvir (Harvoni) is just as effective as a 12-week course for people with hepatitis C virus (HCV) genotype 1 without cirrhosis, including those with HIV/HCV coinfection, and could significantly reduce the cost of treatment if it was prescribed more widely, according to several large real-life cohort studies presented the 2016 AASLD Liver Meeting last month in Boston.
The U.S. Food and Drug Administration (FDA) indication states that the usual course of treatment with sofosbuvir/ledipasvir is 12 weeks, but an 8-week course 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 3 ION-3 trial, but has not been confirmed in real-world clinical practice.
Furthermore, some liver specialists are skeptical about the effectiveness of an 8-week course of sofosbuvir/ledipasvir for people with HIV/HCV coinfection who do not have cirrhosis. The ION-3 study of this regimen excluded people with coinfection, and the ION-4 study of coinfected patients only tested a 12-week course, leading to an absence of evidence on the question. Cohort data have also been lacking, with the exception of data from the German GECCO multicenter cohort, which showed a very high cure rate (98.5%) in a small number of patients.
Three studies presented at the Liver Meeting provided reassuring evidence on the use of an 8-week treatment course in real-life for people with high HCV viral load and people with HIV/HCV coinfection.
8-Week Regimen Pooled Analysis
The largest study was designed to determine the effectiveness of an 8-week sofosbuvir/ledipasvir regimen in people who met the FDA criteria for the shorter course, and to identify predictors of relapse.
The analysis pooled data from 4 cohorts: Burman’s Pharmacy (n=307), Kaiser Permanente Southern California (n=203), the Institute for Interdisciplinary Medicine in 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 whom 798 people met the FDA eligibility criteria. 61 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; 63% were white, 25% were African-American, and 10% were Hispanic. Approximately two-thirds had harder-to-treat HCV genotype 1a, and the vast majority (83%) had less advanced fibrosis (stage F0-F2).
The per-protocol analysis showed that 98.5% of people treated according to the FDA guidance achieved sustained virological response at 12 weeks post-treatment (SVR12). Sub-group analyses showed that at least 95% 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 6 additional studies reporting comparative outcomes among people treated with sofosbuvir/ledipasvir for 8 or 12 weeks. The pooled population comprised 5637 people, and per-protocol SVR12 rates were 95.8% for those treated for 8 weeks and 97.2% for those treated for 12 weeks, a non-significant difference. There was also 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 with sofosbuvir/ledipasvir for 8 weeks enjoy cure rates comparable to those of people treated for 12 weeks. The Deutsches Hepatitis C-Register is a prospective registry of hepatitis C treatment outcomes for people treated with direct-acting antivirals.
Of 8090 people who started treatment between February 1, 2014 and June 30, 2016, 2543 people with HCV genotype 1 infection had completed an 8- or 12-week course of sofosbuvir/ledipasvir according to protocol and had SVR follow-up data.
A total of 976 people received an 8-week course and 1509 people received a 12-week course. Those who received the 12-week regimen were an average of 4 years older and had higher liver stiffness fibrosis measurements. However, because this analysis excluded people who received ribavirin, the proportion of people in the 12-week group who had cirrhosis was low (12%). In the 12-week group, 59% had previous treatment experience.
The analysis showed that 98% of each group achieved SVR12. The cohort included 278 people with HIV/HCV coinfection: 9% in the 8-week group and 12% in the 12-week group. SVR12 rates were 98% for the coinfected groups treated for 8 weeks and for 12 weeks.
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). Baseline 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 for HIV/HCV Coinfection
An open-label Phase 3b study conducted in Russia and Estonia also found no substantial difference in outcomes between previously untreated people with HIV/HCV coinfection or HCV monoinfection treated with sofosbuvir/ledipasvir for 8 weeks.
The study population comprised 67 people with HCV monoinfection and 59 people with HIV/HCV coinfection, 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 IU/mL in the coinfection group).
All participants (100%) in the HCV monoinfection arm and 57 of 59 people (97%) in the HIV/HCV coinfection arm achieved SVR12. Both cases of virological failure occurred in people with genotype 1a.
V Sundaram, C Jeon, KV Kowdley, 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 totaling >6,500 patients. AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract LB-16.
P Buggisch, KH Boeker, R Günther, et al. 8 weeks treatment under real life conditions with ledipasvir/sofosbuvir in HIV co infected treatment-naive HCV genotype 1 infected patients with similar results to mono-infected HCV patients: data from the German Hepatitis C-Registry (DHC-R). AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract 883.
V Isakov, N Gankina, R Salupere, et al. Ledipasvir/sofosbuvir for 8 weeks results in high SVR rates in treatment-naive patients with chronic HCV infection and HIV/HCV coinfection. AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract 2030.