Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort

Abstract

Objective: We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.

Design: Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child-Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI -2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.

Conclusions: DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.

Trial registration number: NCT02097966.

Keywords: ANTIVIRAL THERAPY; CHRONIC VIRAL HEPATITIS; CIRRHOSIS; HEPATITIS C.

Figure 1

Patient disposition by treatment group. Patient disposition by treatment group and reasons for non-completion of 24 weeks of therapy and discontinuation of follow-up are shown. Data for patients who did not reach post-treatment week 12 due to virological failure (n=2 in each group) or who died after achieving sustained virological response at post-treatment week 12 (SVR12) (n=4) are not shown. Patients who discontinued treatment prematurely could continue to be followed. Discontinuations before follow-up week 12 include patients who stopped treatment prematurely and did not continue follow-up (on-treatment death, lost to follow-up and withdrew consent) and those who discontinued after completing treatment. In the daclatasvir (DCV)+sofosbuvir (SOF) group, three patients excluded from the modified intention-to-treat (mITT) population had HCV RNA

Figure 2

Sustained virological response at post-treatment week 12 (SVR12) (as-observed) by baseline characteristics. SVR12 rates and 95% CIs by subgroups are shown for the as-observed population, which includes patients with data available on or after post-treatment week 12, including those with virological failure. Data not shown for patients infected with genotype 2 (n=2), genotype 5 (n=1), mixed genotypes (n=1) or unknown genotype (n=2) and patients with Model for End-Stage Liver Disease (MELD) score >20 (n=3); all achieved SVR12. CrCl, creatinine clearance; DCV, daclatasvir; RBV, ribavirin; SOF, sofosbuvir.

Figure 3

Sustained virological response at post-treatment week 12 (SVR12) (modified intention-to-treat (mITT)) in patients with HCV genotype 3 infection. SVR12 (mITT analysis) rates by treatment group in genotype 3-infected patients are shown according to baseline cirrhosis status and prior HCV therapy (A) and disease stage in patients with cirrhosis (B). Error bars indicate 95% CIs. Data for patients with cirrhosis status indeterminate (n=7, all achieved SVR12) or not reported (n=1, relapse) and for one patient with Model for End-Stage Liver Disease (MELD) score not reported (discontinuation due to adverse event, imputed as failure) are not shown. DCV, daclatasvir; RBV, ribavirin; SOF, sofosbuvir.

Figure 4

Changes in Model for End-Stage Liver Disease (MELD) score from baseline to post-treatment week 12. Changes in MELD score from baseline to post-treatment week 12, by baseline Child–Pugh class, are shown. Each panel indicates the numbers of patients according to the magnitude of change in MELD score. Solid bars indicate patients who achieved sustained virological response at post-treatment week 12; hatched bars indicate patients with virological failure.