Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real-world cohort study

Hepatology. 2016 Dec;64(6):1893-1899. doi: 10.1002/hep.28782. Epub 2016 Oct 5.

Abstract

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton-pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real-world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per-protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity-matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low- nor high-dose PPI was associated with decreased SVR, although patients taking twice-daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0-97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice-daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02-0.59).

Conclusion: These data from a cohort of real-world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low-dose (20-mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893-1899).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use*
  • Cohort Studies
  • Drug Interactions
  • Female
  • Fluorenes / pharmacology
  • Fluorenes / therapeutic use*
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • Sofosbuvir / pharmacology
  • Sofosbuvir / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • Proton Pump Inhibitors
  • ledipasvir
  • Ribavirin
  • Sofosbuvir