Real‐life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance‐associated substitution test

Abstract

This study aimed to investigate the real‐life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention‐to‐treat (ITT) and per‐protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or “undetermined” (4%) resistance‐associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment‐naive patients and 93.2% and 95.6% in treatment‐experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with “undetermined RAS” (85.7%) or “not tested for RAS” (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty‐two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV‐infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.

Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea

“…In the initial phase of DAA introduction in Korea, most patients with GT 1b infection were treated with DCV+ASN or LED/SOF, while those with GT 2 infection were treated with SOF+RBV. Although the SVR rates of genotype-specific DAAs were as high as 94.2-96.2%, 11,12 36 patients with virological failure in DAA were identified in this study. Baseline NS5A RAS significantly lowered the SVR rate in patients treated with DCV+ASN (65.4% vs. 94.3%) 20 in a previous clinical trial.…”

“…9 Since the first DAA, daclatasvir+asunaprevir (DCV+ASN) was approved and reimbursed in 2015 for patients with GT 1b with mandatory RAS testing and results of an absence of NS5A RAS L31 and Y93, which showed a real-life SVR rate of 94.8−96.3%. 10,11 Due to cost issues, sofosbuvir/ledipasvir (SOF/LDV) was reimbursed for GT 1 patients not indicated for DCV+ASN. The SOF+ribavirin (RBV) was reimbursed for GT 2 with a reported SVR rate of 94.2%.…”