Does Concomitant PPI Use Affect Efficacy of Elbasvir/Grazoprevir?
BOSTON, MA—Consistent concomitant use of proton pump inhibitors (PPIs) with elbasvir/grazoprevir (EBR/GZR) had no clinically significant effect on 12-week sustained viral response (SVR12) rates in patients with hepatitis C virus (HCV) genotype (GT)1 or GT4 infection with and without cirrhosis, according to research presented at The Liver Meeting® 2016.
“Furthermore, consistent PPI use was not associated with changes in SVR12 rates in subjects based on age, cirrhotic state, HCV genotype, baseline viral load, or the presence of baseline resistance-associated variants,” noted Nancy Reau, MD, chief of the section of hepatology at Rush University Medical Center in Chicago, IL, and coauthors.
Up to one-third of patients with HCV use some acid reducers, including PPIs. Concomitant PPIs with some NS5A inhibitors can affect the pharmacokinetics (PK) of direct-acting antiviral (DAA) agents, possibly reducing efficacy. Phase 1 study data showed no effect of PPIs on the PK of EBR/GZR in healthy volunteers.
Dr. Reau and colleagues conducted a post hoc analysis of six Phase 3 studies in the clinical program for EBR/GZR, assessing SVR12 in patients with self-reported PPI use and EBR/GZR PK. The trials included both treatment-naive and treatment-experienced patients with or without compensated cirrhosis.
“The analysis incorporated data from only those Phase 3 trials in which the marketed FDC tablet of EBR/GZR (which included the enabled formulation of EBR) was used,” she noted. The EBR population PK data were available for analysis from 5 of the 6 studies.
"Self-reported consistent baseline PPI use was defined as ≥7 consecutive days of use between Day -7 and Day 7," they noted. Additional analyses assessed PPI use and other factors related to SVR, with gender, age, cirrhosis status, prior treatment status, baseline HCV RNA, HCV GT, and baseline resistance associated variants (RAVs) as variables.
The modified full analysis set population included 1322 patients, 65.2% of whom were male and 72.5% were white. Mean age was 51.1 years, mean BMI was 26.3 kg/m2 (range 11.0, 52.8), and 21.5% had cirrhosis. The majority of patients (80.7%) was treatment-naïve; 68.4% had a baseline HCV RNA >800,000 IU/mL. A total of 56.6% were HCV GT1a; 36.4%, GT1b; and 7.0%, GT4; 13.3% had baseline RAVs.
Overall, 12% (n=162) of patients treated with EBR/GZR reported baseline use of PPIs, of which 95.7% (n=155) achieved SVR12. In patients who did not use PPIs, 97.3% (n=1,129) achieved SVR12. The SVR12 rates were lowest among patients with consistent baseline PPI use and HCV GT4, 85.7% (6 of 7 patients), and with baseline RAVs present, 82.4% (14 of 17 patients); however, consistent PPI usage was not a statistically significant effect.
“The results of this post hoc analysis showed that PPIs taken concomitantly for at least 7 consecutive days were not associated with reduced SVR12 rates with EBR/GZR treatment,” the authors noted.
“When included in logistic regression analyses, consistent PPI use was not a predictive factor in SVR12 achievement, even after adjusting for effects known to be associated with SVR12 or for which there was an imbalance between consistent PPI users and inconsistent PPI users,” they added.
These results were further supported by population PK results, which demonstrated there was “no correlation between consistent PPI use, EBR AUC0-24, and SVR12 rate.”