Effectiveness of Glecaprevir/Pibrentasvir in Patients with Chronic HCV-infection Genotypes 1 to 6 in the real-world settings in Russia (EVEREST study)

Abstract

Background: Glecaprevir/pibrentasvir (GLE/PIB) is the first pangenotypic ribavirin-free regimen allowing for treatment duration as short as 8 weeks for the majority of patients with chronic hepatitis C (CHC) genotypes (GT) 1 to 6. The results of clinical trials showed good tolerability of GLE/PIB and high virologic response rate (mostly >95%) among different patient populations. The main objective of this study was to determine how the efficacy and safety of GLE/PIB translates into real-world clinical settings in Russia.Materials and Methods: This was a prospective, multicenter observational study in patients with CHC who received the GLE/PIB regimen. The treatment regimen was prescribed by a physician in accordance with all applicable requirements before the enrollment in the study. Patients were observed for the duration of GLE/PIB therapy and at least for up to 12 weeks after the treatment completion. Real-world data were collected in patient records. Follow-up visits, procedures, and diagnostic methods followed physicians’ routine clinical practice.Results: Overall 161 patients were enrolled in the study in 11 study sites of them 128 patients had sufficient follow-up data to assess sustained virological response 12 weeks [i.e. ≥70 days] after the end of treatment with GLE/PIB (SVR12). Overall, 127 out of 128 patients (99.2%) achieved SVR12. Depending on treatment duration the following SVR12 rates were achieved: 98.7% in 8-week group (75/76), 100% in 12-week group (49/49) and 100% in 16-week group (3/3). One patient failed to achieve SVR, the exact reasons of failure couldn’t be established by the Investigator.Since only one patient didn’t achieve primary endpoint the following SVR12 rates were achieved in different subpopulations: 91.7% in patients with GT2 (11/12); 98.9% in non-cirrhotic patients (88/89); 99.1% in treatment-naïve patients (113/114); 99.1% in patients without HIV co-infection (116/117); 99.2% in patients younger than 65 years (120/121).On the other hand, SVR12 was achieved by all patients (100%) in the following subpopulations: patients with GT3 (n=76), GT1a (n=5), GT1b (n=29) and other GTs (n=6); cirrhotic patients (n=36) and those with unknown cirrhosis status (n=3); treatment-experienced patients (n=14); HIV/HCV co-infected patients (n=11); patients older than 65 years (n=7); and drug users (n=10).No clinically significant abnormalities in the key laboratory parameters were noted during the study. On contrary, the overall improvement of the liver enzymes was observed at SVR12 Visit. There were 3 patients with 3 adverse events (AEs): 2 cases were mild (cough and rash), and 1 case was severe and evaluated as a serious AE (hepatic decompensation). Hepatic decompensation led to the patient withdrawal from the study; this serious AE was preceded by 2 months of daily alcohol consumption and in the investigator’s opinion was not related to GLE/PIB intake. Of all AEs only rash was related to GLE/PIB administration according to investigator’s opinion.Conclusion: GLE/PIB has proven to be a highly effective treatment regimen in the routine clinical practice in patients with all hepatitis C virus genotypes, including those with GT3 and compensated liver cirrhosis. SVR12 rates demonstrated in this study are fully consistent with the previously published data. The regimen was well tolerated by patients.