Introduction
Proton pump inhibitors (PPIs) are among the most commonly prescribed drug classes in most western countries. Their clinical effect is mediated by inhibition of acid secretion from stomach parietal cells, and relieve gastro-esophageal reflux disease, peptic ulcers, and dyspepsia (1). Despite the perceived safety of PPIs, increasing evidence links PPI treatment to bacterial enteritis, and clostridium difficile enterocolitis (2). Alteration of gut microbiota seems to be the common denominator of these adverse outcomes (3), which may trigger inflammation in IBD (4). Several studies link proton pump inhibitor (PPI) use and adverse outcomes in patients with inflammatory bowel disease (IBD) (5-7). On the other hand, PPI prescription may also mark the onset of symptoms from IBD flare-ups, and in that case indicate confounding by indication – a protopathic bias. Thus, it remains unresolved whether PPI use have an adverse impact on the clinical course of IBD, or whether an association between PPI use and deterioration of IBD is the result of a protopathic bias. An analysis of the interaction between time since PPI prescription and the adverse outcomes would aid to the clarification of that (8).
Aims & Methods
We aimed study the association between PPI use and hospitalizations/surgery in IBD patients.
We identified all Danish residents diagnosed with IBD in 2000–2018 in a nationwide healthcare register (18). The data were analyzed as separate PPI treatment episodes allowing an individual to enter with more than one PPI episode. We used propensity score weighted Cox regression to estimate the hazard ratio (HR) for hospitalization and surgery for PPI-users compared with non-users adjusted for age, sex, IBD duration, calendar year of diagnosis, disease category (Crohn’s disease / Ulcerative colitis), Charlson Comorbidity Index score, previous IBD-related hospitalizations, previous IBD-related surgery, maintenance therapy (5-aminosalicyclic, thiopurines or anti-tumor necrosis factor-a agents [infliximab/adalimumab], and prescription of NSAIDs).
Results
We identified 40,767 patients with IBD (69.2% with ulcerative colitis, 30.8% with Crohn’s disease). Before first IBD diagnosis, 34.0% had filed at least one PPI prescription. Five years after IBD diagnosis, 39.9% had had at least one PPI prescription. The weighted HR for hospitalizations was 1.71 (95% CI: 1.62–1.81) during the first year after PPI prescription, and 1.33 (95 % CI: 1.18–1.50) thereafter. The weighted HR for IBD-related surgery was 1.39 (95% CI: 1.18–1.50) the first year and 1.40 (95% CI: 1.20–1.64) thereafter.
Conclusion
We identified a 40–70% higher rate of hospitalization and surgery the first year after PPI prescription in IBD patients, and a 10–30% higher rate for the remaining follow-up.
References
References
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