Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials

Abstract

Background & aims: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non-adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non-adherence on sustained virological response at post-treatment week 12 (SVR12) rates in HCV genotype (GT) 1-6-infected patients.

Methods: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non-adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent-to-treat (ITT) population and modified ITT (mITT) population, which excludes non-virological failures.

Results: Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non-adherence to G/P therapy (OR: 2.38; 95% CI: 1.13-5.01; P = .022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P = .047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively.

Conclusions: Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment.

Clinical trials registration: NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717.

Keywords: G/P; adherence; glecaprevir; hepatitis C virus; pibrentasvir.

Conflict of interest statement

A Brown: Advisor and speaker for, and recipient of research grants from, AbbVie, Bristol‐Meyers Squibb, Janssen, Gilead Sciences and MSD. TM Welzel: Consultant or speaker for AbbVie, Boehringer Ingelheim, Bristol‐Myers Squibb, Gilead Sciences and Janssen. B Conway: Research and grant support from, and participation in advisory boards for, AbbVie, Bristol‐Myers Squibb, Gilead Sciences, Janssen and Merck. F Negro: Grant support from Gilead Sciences; advisor for AbbVie, Gilead Sciences and Merck. N Bräu: Advisor and speaker for, and received grant support from, AbbVie, Bristol‐Myers Squibb, Gilead Sciences and Merck. J Grebely: Consultant/advisor for, or received grant support from, AbbVie, Cepheid, Gilead Sciences, and Merck/MSD. M Puoti: Temporary advisory board and/or speaker at own events for AbbVie, BMS, Boehringer Ingelheim, Janssen, Gilead Sciences, MSD and Roche; research support from Gilead Sciences and MSD. A Aghemo: Grant support from Gilead Sciences and AbbVie; advisory board and speaker for AbbVie, BMS, Gilead Sciences, Janssen and MSD. H Kleine, D Pugatch, FJ Mensa, YJ Chen, Y Lei: current or former employees of AbbVie, Inc; may own AbbVie stock and/or options. E Lawitz: Consultant, advisor and speaker for, or received research/grant support from AbbVie and Gilead Sciences, T Asselah: Clinical investigator, speaker and consultant for AbbVie, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Roche.

© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.

Figures

Figure 1

Sustained virological response at post‐treatment week 12 by adherence to G/P therapy and treatment duration in (A) intent‐to‐treat and (B) modified intent‐to‐treat populations Adherent: defined as a lowest treatment adherence of ≥80% and ≤120% at each study visit. Non‐adherent: defined as a lowest treatment adherence of 120% in at least one study visit. Error bars: two‐sided 95% CIs using the Wilson score method for binomial proportions. Intent‐to‐treat population: defined as all patients who received at least one dose of study drug. Modified intent‐to‐treat population: excludes non‐virological failures. P values were calculated using the chi‐squared test (or Fisher's exact test if ≥25% of the cells had expected counts <5) using non‐missing values. Abbreviations: CI, confidence interval; G/P, coformulated glecaprevir/pibrentasvir 300/120 mg; SVR12, sustained virological response at post‐treatment week 12