Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection

Abstract

Background and Aims Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end‐stage renal disease (ESRD). Previously available direct‐acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. Methods EXPEDITION‐5 is a phase 3 study to evaluate efficacy and safety of the fixed‐dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post‐treatment (SVR12). Results Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty‐four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty‐five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6‐99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug. Conclusions G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected. Clinicaltrials.gov identifier This Phase 3 clinical trial was funded by AbbVie and registered with http://www.clinicaltrials.gov as NCT03069365 (EXPEDITION‐5).

Renal function in HCV therapy: Just another thing to ignore?

“…Adverse events were reported in 5% of patients and include pruritus, hypertension, generalised pruritus and bronchitis. Consistent to the findings of the EXPEDITION‐4 trial, kidney function remains unchanged during treatment up to post‐treatment week 4 in dialysis‐independent patients …”

Is an 8‐week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real‐world experience?

“…9 No specific safety issues were observed during the treatment course, and we confirmed a favorable safety profile of the 8-week GLE/PIB regimen, which supported similar findings from clinical trials and other real-world studies. 21,22,[27][28][29][30][31][32] We are aware of some limitations of the current study related to its real-world nature, which include its observational type and retrospective design with possible bias associated with under-reporting or incomplete information, inconsistent diagnosis or misclassification of data, underestimation of the adverse event rate, and possible data entry errors due to the electronic data capture system. The limited number of GT3-infected patients with compensated liver cirrhosis is probably the major weakness of our analysis, and it is caused by the fact that the possibility for a shorter, 8-week treatment course has emerged very recently.…”

Efficacy and Safety of Glecaprevir/Pibrentasvir for Chronic Hepatitis C Patients: A Systematic Review and Meta-analysis

“…Overall, 25 studies (21 publications and 4 unpublished clinical trials; ClinicalTrials.gov Nos. NCT02707952 substudy1, 3 NCT02723084, 4 NCT02604017, 5 NCT02640482, 6 NCT02640157, 5 NCT02636595, 6 , 7 NCT02966795, 8 NCT02642432, 9 NCT02738138, 10 NCT02651194, 11 NCT03069365, 12 NCT03089944, 13 NCT02446717, 14 , 15 NCT02692703, 16 NCT03117569, 17 NCT02243293, 6 , 18 , 19 NCT03222583, 20 NCT03235349, 21 NCT03092375, 22 NCT03212521, 23 NCT03219216 24 ) were included in this review. A flow chart of the study selection is presented in Fig.…”