Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme

Abstract

Background & AimsOptimally effective treatment for hepatitis C virus genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real‐world data for daclatasvir+sofosbuvir in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization.MethodsPatients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post‐liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400 mg daily) for a recommended duration of 24 weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post‐treatment week 12 (SVR12; modified intention‐to‐treat). Safety was assessed by spontaneous adverse event reporting.ResultsThe efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24 weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6‐92.5%), 98% (43/44) without cirrhosis (95% CI 88.2‐99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5‐90.7%), without SVR12 increase in those who received additional ribavirin for 24 weeks (SVR12 82% [50/61; 95% CI 70.5‐89.6%]). Among 516 GT3‐infected patients with safety data, 5 discontinued for adverse events and 11 died.ConclusionsDaclatasvir+sofosbuvir achieved high SVR12 rates and was well tolerated in this large real‐world cohort of GT3‐infected patients with advanced liver disease, without benefit of ribavirin in those treated 24 weeks.

Treatment of hepatitis C: Results in real life

“…Results of clinical trials are discordant on the benefit of adding ribavirin and real‐world data vary, with some studies showing that it is beneficial in this setting while others do not. In a French early access program including 333 patients with genotype 3‐infection, the addition of ribavirin to treatment with sofosbuvir plus daclatasvir for 24 weeks did not provide any additional benefit to either patients without cirrhosis (SVR12 83% vs SVR24 98%) or those with cirrhosis (SVR12 82% vs SVR24 86%) …”

“…Other real‐world data show that sofosbuvir plus daclatasvir (± ribavirin) is associated with an overall SVR12 rate of 88%‐96% in genotype 3 infection, with lower response rates in treatment‐experienced patients and those with cirrhosis . These findings are consistent with EASL guidelines, which have different recommendations for this combination in genotype 3‐infected patients depending on the status of cirrhosis .…”

“…Existing results show that certain subpopulations are still difficult to treat and the role of ribavirin and the optimal treatment duration must be clarified. Evidence suggests that patients with cirrhosis with genotypes 1b and 3 infection and those coinfected with HIV are still difficult to treat …”

Polymorphism in interferon λ3/interleukin‐28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy

“…Nelson et al reported a 96% SVR12 rate in genotype 3 HCV patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Similarly, Hezode et al also reported higher (98%) SVR12 rates in genotype 3 HCV patients without cirrhosis (98%; 43 of 44). In our study, the SVR (87.6%) rate in genotype 3 HCV patients without cirrhosis is slightly lower compared with the above study.…”

A case of genotype‐3b hepatitis C virus in which the whole genome was successfully analyzed using third‐generation nanopore sequencing

“…In fact, the present patient was from China, and fortunately achieved SVR following direct‐acting antiviral (DAA) therapy with glecaprevir plus pibrentasvir. The therapeutic efficacies of DAAs, however, have been shown to be inferior in patients with genotype 3 HCV, compared with the efficacies in patients infected with other HCV genotypes, and the viral factors involved in this unfavorable outcome have yet to be clarified. Genotype 3 HCV strains consist of various subgenotypes, and only a few reports regarding the genome sequences of genotype 3 HCV have been published, as universal primers suitable for any subgenotype strain cannot be designed.…”