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Proton pump inhibitors and the risk of inflammatory bowel disease: cause, protopathic bias or others?
  1. Byong Duk Ye1,2
  1. 1 Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
  2. 2 Inflammatory Bowel Disease Center, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
  1. Correspondence to Professor Byong Duk Ye, Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of); bdye{at}

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Proton pump inhibitors (PPIs) were introduced in the late 1980s, and they have since been widely used for treating various conditions such as gastro-oesophageal reflux disease and peptic ulcer disease.1 However, PPIs may pose health risks if they are used frequently or overprescribed, especially over a prolonged period.2 In particular, PPIs have been associated with increased risks of several undesirable conditions, including pneumonia, myocardial infarction, renal diseases, bone fractures, dementia, gastrointestinal malignancies and enteric infections including Clostridioides difficile infection.3–5 In addition, recent observational studies have suggested an association between the use of PPIs and the incidence of inflammatory bowel disease (IBD).6 7 In a nested case–control study performed in the USA, 285 new cases of IBD and 1142 matched controls, both aged ≤21 years, were enrolled between 1996 and 2016 to investigate the association between acid-suppressing therapy and IBD development.6 Six patients in each of the IBD patient and control groups were prescribed at least one PPI 2–5 years before IBD diagnosis; the adjusted OR for association between PPI use and IBD incidence was 3.6 (95% CI 1.1 to 11.7). However, it was hard to draw firm conclusions from these results owing to the small number of PPI-exposed individuals and the enrolment of only paediatric and adolescent-onset IBD cases. More recently, through a pooled analysis of the Nurses’ Health Study I and II together with the UK Biobank data, comprising a study population of over 640 000, regular use of PPIs was associated with an increased risk of IBD (HR 1.42, 95% CI 1.22 to 1.65) compared with that of non-users.7 When directly compared with users of histamine-2 receptor antagonists (H2RAs), PPI use was associated with a higher risk of IBD development (HR 1.38, 95% CI 1.16 to 1.65). However, this study used a self-reported survey …

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  • Contributors BDY wrote the manuscript and is the guarantor.

  • Funding This work was supported by the National Research Foundation of Korea (grant no. 2021R1A2C2095096) funded by the Ministry of Science and ICT, the Republic of Korea.

  • Competing interests BDY has received research grants from Celltrion and Pfizer Korea; consulting fees from AbbVie Korea, BMS Pharmaceutical Korea, Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES, Pfizer Korea, Samsung Bioepis, Takeda and Takeda Korea; and speaking fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea and Takeda Korea. None of these disclosures are directly associated with this study.

  • Provenance and peer review Commissioned; externally peer reviewed.

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