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Concomitant Proton Pump Inhibitor Use Does Not Reduce the Efficacy of Elbasvir/Grazoprevir
( Nancy Reau ),( Michael Robertson ),( Hwa-ping Feng ),( Luzelena Caro ),( Wendy W. Yeh ),( Bach-yen T. Nguyen ),( Janice Wahl ),( Eliav Barr ),( Peggy Hwang ),( Stephanie O. Klopfer ),( Youngmi Eun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: It is estimated that up to one-third of hepatitis-C virus (HCV)-infected patients use proton pump inhibitors (PPIs) and other acid reducing agents. Concomitant PPI use with some NS5A inhibitors impacts the pharmacokinetics (PK) of direct-acting antiviral agents (DAAs), potentially reducing efficacy. Phase I study results demonstrated no effect of PPI use on the PK of the fixed-dose combination of elbasvir/grazoprevir (EBR/GZR) in healthy volunteers. This post hoc analysis of studies in the Phase 3 clinical program of EBR/GZR assessed the 12-week sustained viral response (SVR12) in subjects with self-reported PPI use and the PK of EBR/GZR in these patients. Methods: Data were derived from six Phase 3 EBR/GZR trials with treatment-naïve or treatment experienced GT1/4-infected subjects, with or without cirrhosis. Analyses were done in the modified Full Analysis Set population (excludes administrative discontinuations). Self-reported baseline PPI use was defined as ≥7 consecutive days of use between Day -7 and Day 7. Bivariate analyses assessed PPI use and other factors associated with SVR, with gender, age (continuous and dichotomous), cirrhosis status, prior treatment status, baseline HCV RNA (continuous and dichotomous), HCV genotype, and baseline resistance associated variants as variables in the models. Results: Overall, 12% (162/1322) of EBR/GZR-treated subjects reported baseline use of PPIs. Of those, 155/162 (96%) achieved SVR12. In patients without PPI use, 1129/1160 (97%) achieved SVR12. PPI use was not a predictive factor in achieving SVR12 based on a univariate analysis (p = 0.188). In the bivariate models, none of the interaction terms was statistically significant, indicating that any potential effects of PPI were consistent across the factors considered. In addition, PPI usage was not a statistically significant effect, regardless of adjustment for the factors considered. From 3 of the 6 studies for which population PK data were available, the estimated AUC and Cmax values for EBR were comparable among patients with and without reported PPI use (table). Conclusions: These results demonstrate that PPIs use with EBR/GZR has no clinically significant effect on SVR12 rates in GT1/4-infected patients with and without cirrhosis.