Efficacy of generic oral directly acting agents in patients with hepatitis C virus infection

Abstract

Novel direct-acting antivirals (DAAs) are now the standard of care for the management of hepatitis C virus (HCV) infection. Branded DAAs are associated with high sustained virological response at 12 weeks post-completion of therapy (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in a real-life clinical scenario. Consecutive patients with known HCV infection who were treated with generic-oral DAA regimens (May 2015 to January 2017) were included. Demographic details, prior therapy and SVR12 were documented. Four hundred and ninety patients (mean age: 38.9 ± 12.7 years) were treated with generic DAAs in the study time period. Their clinical presentations included chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120 (24.48%) cases and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was most common (n = 372, 75.9%) followed by genotype 1 (n = 97, 19.8%). Treatment naïve and treatment-experienced (defined as having previous treatment with peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%), respectively. Generic DAA treatment regimens included sofosbuvir in combination with ribavirin (n = 175), daclatasvir alone (n = 149), ribavirin and peginterferon (n = 80), ledipasvir alone (n = 43), daclatasvir and ribavirin (n = 37), and ledipasvir and ribavirin (n = 6). Overall SVR12 was 95.9% (470/490) for all treatment regimens. SVR12 for treatment naïve and experienced patients was 97.0% (419/432) and 87.9% (51/58), respectively, P = .005. High SVR12 was observed with various regimens, irrespective of genotype and underlying liver disease status. There were no differences in SVR12 with 12 or 24 weeks therapy. No major adverse event occurred requiring treatment stoppage. Generic oral DAAs are associated with high SVR rates in patients with HCV infection in a real-life clinical scenario.

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

“…In the present study, 10 decompensated LC patients were treated with DCV/ASV combination therapy, and all of them showed a successful SVR of 87.5% (Figure C) and were well tolerated, except 2 patients who stopped the treatment due to nonmedical reasons, as shown in Figure C. Because ASV is not labeled for decompensated cirrhosis, previous data are limited, but a recent study reported 100% of SVR in 10 decompensated cirrhosis, similarly high as our results. Nonetheless, those decompensated LC patients in our study had a stable hepatic function even with a previous history of decompensation were able to tolerate the DCV/ASV combination therapy.…”

Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection

“…Regarding the real‐world experiences of generic IFN‐free DAAs, several reports evaluated the effectiveness and safety of a generic version of SOF in combination with ledipasvir (LDV), daclatasvir (DCV) and/or RBV. The overall SVR rates were excellent (89%‐99%) and most patients tolerated the treatment well . Based on the encouraging results, we aimed to evaluate the effectiveness and safety of a generic version of pan‐genotypic VEL/SOF‐based therapy for HCV infection in patients with or without HIV coinfection.…”

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

“…Although HCV treatment using new‐generation DAAs is very effective, a small proportion (1%‐15%) of patients fail to achieve SVR12 . The intrinsic high replication rate allows HCV to respond rapidly to immune or drug‐induced pressures, facilitating the selection of resistant variants.…”

“…To the best of our knowledge, there is no other systematic re- treatment-emergent substitutions that were detected in NS3 in 50% Subgroup (study references) Although HCV treatment using new-generation DAAs is very effective, a small proportion (1%-15%) of patients fail to achieve SVR12. 37,38 The intrinsic high replication rate allows HCV to respond rapidly to immune or drug-induced pressures, facilitating the selection of resistant variants. The impact of baseline RAS varies across different DAA classes.…”