Abstract

Background: Gastric acid suppressants such as proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RAs) are common gastrointestinal medications used to manage symptoms of acid related diseases. Studies have shown that these medications are associated with increased risk of pneumonia, vitamin deficiency, osteoporosis and fractures. Few studies have described the potential risk of inflammatory bowel disease (IBD) exacerbation among patients on gastric acid suppressants but little is known on its association. This study aims to investigate the effect of the use of gastric acid suppressants (PPI and H2RA) in the risk of IBD (Crohn’s disease and ulcerative colitis) exacerbation.

Methods: A comprehensive, computerized literature search from the electronic database of MEDLINE, Google scholar, Cochrane Library, and OVID was performed with the following search terms: gastric acid suppressants, proton pump inhibitors, histamine-2-receptor antagonists, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, outcomes, and disease activity exacerbation. Two cohort studies were selected and validated using the GRADE and Newcastle-Ottawa criteria. Trial results were combined under a random effects model using pooled adjusted relative risks (RRs). The Cochrane Review Manager Software version 5.4 was used for all analyses.

Results: Two cohort studies comprising of 36,293 patients were analyzed by pooling reported adjusted RRs using the random effects model. Disease activity exacerbation was associated with the use of gastric acid suppressants with pooled adjusted RR 1.14 [95% CI, 1.08 - 1.20, I² = 0%] with no heterogeneity. The effects of PPIs and H2RAs were also separately analyzed. The pooled adjusted RR of IBD activity exacerbation with the use of PPIs was 1.12 [95% CI, 1.05 - 1.19, I² = 0%] for any IBD, while the pooled adjusted RR of disease activity exacerbation with the use of H2RAs was 1.21 [1.04 - 1.40, I² = 42%] for any IBD, with moderate heterogeneity. The effect of acid suppression was more marked in patients with Crohn’s disease, RR 1.44 [0.89 - 2.33, I² = 77%], but this was statistically insignificant with marked heterogeneity; than in ulcerative colitis RR 1.12 [1.05 - 1.20, I² = 0%].

Conclusion: Use of gastric acid suppressants such as PPIs and H2Ras may be associated with increased risk of disease exacerbation in patients with IBD. This meta-analysis confirms the need for further prospective studies in examining this relationship.

Keywords: Proton Pump Inhibitor; Histamine 2 Receptor Antagonist; Inflammatory Bowel Disease

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