Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs

Am J Gastroenterol. 2015 May;110(5):749-59. doi: 10.1038/ajg.2015.119. Epub 2015 Apr 28.

Abstract

Objectives: Microscopic colitis (MC) is characterized by chronic watery diarrhea. Recently, several drugs were reported to increase the risk of MC. However, studies lacked a clear exposure definition, did not address duration relationships, and did not take important biases into account. We estimated the risk of MC during drug use.

Methods: This is a population-based nested case-control study using a Dutch primary care database (1999-2013). Incident MC cases (aged ≥18 years) were matched to community-based and colonoscopy-negative controls on age, sex, and primary care practice. Drug use was assessed within 1 and 2 years before the index date. Adjusted odds ratios (OR) were calculated by conditional logistic regression.

Results: From the source population of 1,458,410 subjects, 218 cases were matched to 15,045 community controls and 475 colonoscopy-negative controls. Current use (≤3 months) of proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors, low-dose aspirin, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers significantly increased the risk of MC compared with never use in community controls. Adjusted ORs ranged from 2.5 (95% confidence interval (CI): 1.5-4.2) for ACE inhibitors to 7.3 (95% CI: 4.5-12.1) for PPIs in the year prior to the index date. After accounting for diagnostic delay, only use of NSAIDs, PPIs, low-dose aspirin, and ACE inhibitors increased the risk of MC. Compared with colonoscopy controls, only use of PPIs (OR-adjusted 10.6; 1.8-64.2) and NSAIDs (OR-adjusted 5.6; 1.2-27.0) increased the risk of MC.

Conclusions: NSAIDs and PPIs are associated with an increased risk of MC. The association of MC with use of the other drugs is probably explained by worsening of diarrhea/symptoms rather than increasing the risk of MC itself.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / administration & dosage
  • Case-Control Studies
  • Colitis, Microscopic / chemically induced
  • Colitis, Microscopic / epidemiology*
  • Colonoscopy
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Odds Ratio
  • Proton Pump Inhibitors / therapeutic use*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • Proton Pump Inhibitors
  • Serotonin Uptake Inhibitors
  • Aspirin