Do Proton Pump Inhibitors Increase Risk for Inflammatory Bowel Disease?

Patients who recently initiated treatment with proton pump inhibitors are not at increased risk for IBD.

While proton pump inhibitors (PPIs) initially increased risk for onset of inflammatory bowel disease (IBD) within the first 2 years after beginning treatment, longer-term assessment suggests that IBD incidence risk following treatment with PPIs or histamine-2 receptor antagonists (H2RAs) is not significantly different, according to study findings published in Gut.

The current rise in PPI use over the past 20 years has increased concern regarding the possible association between PPIs and onset of IBD.

To analyze the relationship between PPIs and IBD, researchers conducted a longitudinal, population-based cohort study, recruiting participants from January 1, 1990 to December 31, 2018 with a follow-up until December 31, 2019. Researchers obtained data from the United Kingdom’s Clinical Practice Research Datalink (CPRD) Gp OnLine Data (GOLD) database.

During the recruitment period, 1,498,416 people initiated PPI treatment, whereas 322,474 people initiated H2RA treatment. Researchers performed an early-event analysis for IBD onset within the first 2 years of initiating PPI or H2RA treatment compared with a late-event analysis for IBD onset after 2 years following initiation of treatment.

Within the first 2 years following PPI treatment initiation, 2313 individuals were diagnosed with IBD compared with the 306 events occurring among those who initiated treatment with H2RAs. Treatment with PPIs increased risk for IBD by 39% within the first 2 years compared with H2RA treatment (hazard ratio [HR], 1.39; 95% CI, 1.14-1.69). Specifically, risk for onset of Crohn disease was elevated within the first 2 years.

This study provides some reassurance on the safety of these drugs on IBD incidence and highlights the importance of accounting for reverse causality…

In contrast, after the 2-year initial period, PPI use was not significantly associated with IBD incidence compared with H2RA use (HR, 1.05; 95% CI, 0.90-1.22). Median follow-up time was 4.2 years (including the 2-year initial period) after treatment initiation for the late-event analysis.

During this time, 2841 cases of IBD among PPI users and 675 cases of IBD among H2RA users occurred at weighted incidence rates of 54.3 per 100,000 person-years and 51.8 per 100,000 person-years, respectively. This indicated that cumulative incidence of IBD was similar in both treatment groups.

“This study provides some reassurance on the safety of these drugs on IBD incidence and highlights the importance of accounting for reverse causality, especially in a setting where a disease has known diagnostic delays,” the study authors wrote.

Study limitations include possible exposure misclassification based on the clinicians writing the prescriptions, possible lack of adherence to prescriptions, possible use of over-the-counter drugs, residual confounding factors, and relatively short duration for follow-up.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Abrahami D, Pradhan R, Yin H, et al. Proton pump inhibitors and the risk of inflammatory bowel disease: population-based cohort study. Gut. Published online January 30, 2023. doi:10.1136/gutjnl-2022-328866