Acid suppressant drugs, including proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), are popular drugs used to manage the symptoms of several stomach conditions. While these drugs are considered highly effective, and are among the most prescribed medications worldwide, there is some evidence to suggest that their use might be associated with complications, including an increase in the risk of inflammatory bowel disease (IBD). IBD is a chronic disease that affects the digestive tract and is associated with a decreased quality of life. Over the past decade, the incidence of IBD has substantially grown. Thus, identifying populations that may be at a higher risk of this disease may lessen its burden. To date, the existing evidence on this safety question is limited. Given the severity of IBD and the millions of patients prescribed acid suppressant drugs, addressing this safety question in a timely fashion is warranted Thus, we will conduct a large, population-based cohort study to address this safety question in the real-world setting. We will compare new users of PPIs to new users of H2RAs and follow patients over a 30-year study period to determine whether use of PPIs is associated with an increased risk of IBD. This large study will provide concerned stakeholders with much needed information on the safety profile of these drugs in a timely and cost-effective fashion.
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly prescribed to manage several gastric conditions. Recent safety signals have associated the use of PPIs with an increased risk of inflammatory bowel disease (IBD). This may be mediated by changes to the gut microbiome, which have been associated with the use of PPIs. However, to date, few real-world studies have examined the association between PPIs to IBD. Thus, the objective of this large population-based cohort study is to assess whether the use of PPIs, in comparison to the use of H2RAs, is associated with the incidence of IBD.
To address this question, we will assemble a cohort of patients newly treated with PPIs or H2RAs between 1990 (the first full year that both drugs were available) and 2018, with follow-up until 2019. New users of PPIs will be compared to new users of H2RAs, and all exposures will be lagged by 2 years to account for diagnostic delays associated with IBD. To control for confounding, we will reweigh the cohort using standardized mortality ratio weighting, which will include over 30 covariates in the propensity score models. Patients will be followed from 6 months after the date of their first prescription until an incident diagnosis of IBD, 6 months after switch from PPI to H2RA or vice versa, censored on an incident diagnosis of ischemic colitis or diverticulitis, death from any cause, end of registration, or end of the study period (December 31, 2019), whichever occurs first. Cox proportional hazards models will be used to estimate weighted hazard ratios of incident IBD, comparing PPIs to H2RAs.
The outcome for this study is incident inflammatory bowel disease (IBD), which will be identified using Read codes (Appendix I).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Alain Bitton - Collaborator - McGill University
Devin Abrahami - Collaborator - McGill University
Emily McDonald - Collaborator - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Collaborator - McGill University
Richeek Pradhan - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Russell Yanofsky - Collaborator - McGill University