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Inflammatory bowel disease
Original research
Proton pump inhibitors and the risk of inflammatory bowel disease: population-based cohort study
  1. Devin Abrahami1,
  2. Richeek Pradhan2,3,
  3. Hui Yin3,
  4. Russell Yanofsky4,
  5. Emily Gibson McDonald5,6,
  6. Alain Bitton7,
  7. Laurent Azoulay2,3,8
  1. 1 Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
  3. 3 Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
  4. 4 Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
  5. 5 Medicine, McGill University Health Centre, Montreal, Quebec, Canada
  6. 6 Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada
  7. 7 Medicine, McGill University, Montreal, Quebec, Canada
  8. 8 Gerald Bronfman Department of Oncology, McGill University, Montreal, Québec, Canada
  1. Correspondence to Dr Laurent Azoulay, Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal H3T 1E2, Quebec, Canada; laurent.azoulay{at}mcgill.ca

Abstract

Objective To determine whether the use of proton pump inhibitors (PPIs) compared with the use of histamine-2 receptor antagonists (H2RAs) is associated with an increased risk of inflammatory bowel disease (IBD).

Design Population-based cohort study designed to address the impact of protopathic bias.

Setting General practices contributing data to the UK Clinical Practice Research Datalink GOLD.

Participants 1 498 416 initiators of PPIs and 322 474 initiators of H2RAs from 1 January 1990 to 31 December 2018, with follow-up until 31 December 2019. Patients were analysed according to the timing of the IBD diagnosis after treatment initiation (early vs late).

Main outcome measures Standardised morbidity ratio weighted Cox proportional hazards models were used to estimate marginal HRs and 95% CIs. In the early-event analysis, IBD diagnoses were assessed within the first 2 years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by 2 years to account for latency and minimise protopathic bias.

Results In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first 2 years of treatment initiation, compared with H2RAs (HR 1.39, 95% CI 1.14 to 1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR 1.05, 95% CI 0.90 to 1.22). The results remained consistent in several sensitivity analyses.

Conclusions Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias.

  • EPIDEMIOLOGY

Data availability statement

No data are available. No additional data available.

https://doi.org/10.1136/gutjnl-2022-328866

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    Data availability statement

    No data are available. No additional data available.

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    Footnotes

    • Contributors All authors conceived and designed the study. LA acquired the data. DA, HY and LA did the statistical analyses. All authors analysed and interpreted the data. RY, EGM and AB provided clinical expertise. DA wrote the manuscript, and all authors critically revised the manuscript. All authors approved the final version of the manuscript and agree to be accountable for the accuracy of the work. LA supervised the study and is the guarantor.

    • Funding Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328).

    • Competing interests RP, HY, RY and EGM have no conflicts of interest to disclose. DA is now employed by Pfizer. AB has been a member of Advisory Boards for Abbvie, Pfizer, Takeda, Janssen and Merck, and has received speaker fees from Abbvie, Janssen, Takeda, Pfizer. LA has received consulting and speaking fees from Janssen, Pfizer and Roche for work unrelated to this study.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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