A 3-year follow-up study after treatment with simeprevir in combination with pegylated interferon-α and ribavirin for chronic hepatitis C virus infection

Abstract

BackgroundSimeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union.MethodsThis 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and evaluated the persistence of treatment-emergent NS3/4A protease inhibitor resistance in patients not achieving SVR following treatment with simeprevir plus PR in the parent study. The maintenance of SVR after the last post-therapy follow-up visit of the parent study (LPVPS) was assessed using HCV RNA measurements. The persistence of treatment-emergent NS3 amino acid substitutions in patients with no SVR at LPVPS was assessed using population sequencing. No study medications were administered.ResultsOverall, 249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40 patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled patients who achieved SVR in the parent study maintained SVR until the last available visit in this study (median follow-up time: 35.8 months). The treatment-emergent NS3 amino acid substitutions detected at time of failure in the parent study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the end of this study (median follow-up time: 179.9 weeks [41.3 months]).ConclusionThis 3-year follow-up study provides evidence for the long-term durability of SVR (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3 amino acid substitutions became undetectable in the majority of patients.Trial registrationNCT01349465; ClinicalTrials.gov.Electronic supplementary materialThe online version of this article (10.1186/s12985-018-0936-4) contains supplementary material, which is available to authorized users.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real‐world experience study

“…Addition of DAA to interferon‐based therapy did not exclude the risk of relapse, as it was shown in patients after triple therapy containing either boceprevir or daclatasvir . However according to the most recent study by Zoulim et al all 200 patients who achieved SVR after interferon containing triple therapy with simeprevir maintained SVR until the last available visit with median follow‐up time of 35.8 months.…”

Treatment failure with DAA therapy: Importance of resistance

“…6,7 During longterm follow-up for several years no or only minor NS3 RASs for different PIs were observed. [42][43][44] An exception is the NS3 variant Q80K in HCV subtype 1a-infected patients, which typically persists during long-term follow-up. 45 In contrast, RASs selected on treatment with NS5A inhibitors seem to persist for more than 2 years in >80% of patients.…”

Clinical significance of FBXW7 loss of function in human cancers

“…Studies performed in vitro and in animal models have shown several promising approaches including LNA-antimiRs or small molecule inhibitors of miRNAs (SMIR), which prevent miRNA-target interaction(s). Some of these are developed by Regulus Therapeutics and are currently in clinical trials for the treatment of HCV cancer [ 248 ]. One potential issue may be related to the unintended side effect of miRNAs, since each miRNA has dozens of gene targets.…”