Medication Use and Risk of Microscopic Colitis: A Propensity‐Matched Analysis of US Adults ≥ 50 Years (2014–2024)

BACKGROUND: The association between medications-including non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs) and selective serotonin reuptake inhibitors (SSRIs)-and microscopic colitis (MC) remains controversial. While earlier studies suggested increased risk, more recent analyses have challenged these findings, citing methodological limitations. We evaluated the risk of MC among commonly implicated medications using a large national U.S. METHODS: Using the TriNetX database (2014-2024), we conducted a retrospective cohort study including adults ≥ 50 years with at least one documented healthcare encounter and no prior MC or inflammatory bowel disease. Exposure was defined as ≥ 3 prescriptions within a drug class. Treatment groups (NSAIDs, PPIs, SSRIs, ACE inhibitors [ACEIs], angiotensin receptor blockers [ARBs], statins) were 1:1 propensity score-matched (PSM) to untreated controls on age, sex, race, comorbidities and previous colonoscopy. The primary outcome was incident MC, identified by new diagnostic codes. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After PSM, cohorts included 907,266 NSAID, 750,009 PPI, 308,310 SSRI, 393,952 ACEI, 298,480 ARB users and 548,339 statin users. Over 2 years, MC risk was increased with NSAIDs (HR 1.15; 95% CI, 1.02-1.30), PPIs (HR 1.36; 95% CI, 1.19-1.54) and SSRIs (HR 1.52; 95% CI, 1.27-1.83). ACEIs, ARBs and statins were not associated with MC. CONCLUSIONS: In this large cohort, NSAIDs, PPIs and SSRIs were associated with an increased risk of MC, whereas no significant association was observed for ACEIs, ARBs or statins. Medication review should be considered in patients with new-onset chronic diarrhoea.