Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs.
OBJECTIVE
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.
1] Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Gwen M C
GM
Masclee
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Preciosa M
PM
Coloma
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ernst J
EJ
Kuipers
1] Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Miriam C J M
MC
Sturkenboom
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage; D016022:Case-Control Studies; D046728:Colitis, Microscopic / Q000139:chemically induced / Q000453:epidemiology*; D003113:Colonoscopy; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D054328:Proton Pump Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors