Commonly cited medication triggers may not increase risk of microscopic colitis among older adults

1. In this series of target trial emulations, several common medications were not found to significantly affect the risk of microscopic colitis in older adults.

2. Comparing selective serotonin receptor inhibitor versus mirtazapine initiation resulted in a small risk difference, which may have been due to surveillance bias.

Evidence Rating Level: 2 (Good)

Study Rundown: Medications are considered a major modifiable risk factor for microscopic colitis (MC), a chronic inflammatory bowel disease that accounts for nearly a third of cases of chronic diarrhea in people aged 65 years or older. However, existing guidelines recommending the discontinuation of potential pharmacologic triggers are largely based on small case-control and cross-sectional studies with bias-prone study designs rather than population-based studies. This study aimed to address this evidence gap by describing the effects of potential pharmacologic triggers on MC risk in a nationwide cohort of older adults in Sweden. Under all treatment strategies, the risk of MC at one year and two years’ follow-up remained below half of a percentage point. There were virtually no risk differences after starting common medications such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, proton pump inhibitors, and non-steroidal anti-inflammatory drugs. While selective serotonin reuptake inhibitors were associated with a modest increase in risk for MC, there was a concurrent increase in risk for receiving colonoscopy with normal biopsy, suggesting that this apparent difference may have been secondary to residual differences in surveillance. The generalizability of this study was limited by a lack of data regarding primary care visits, endoscopic procedures, and lifestyle factors such as smoking and body mass index. Nevertheless, this study suggested a lack of association between the use of commonly suspected pharmacological triggers and risk of MC in older adults, highlighting the need for stronger evidence to guide recommendations.

Click to read the study in AIM

Relevant Reading: Drug Exposure and Risk of Microscopic Colitis: A Nationwide Danish Case–Control Study with 5751 Cases

In-Depth [retrospective cohort]: This series of target trial emulations aimed to estimate the effect of multiple suspected pharmacological triggers on the risk of MC among a nation-wide cohort of older adults in Sweden. Participants were identified through Sweden’s Total Population Register as well as the ESPRESSO study, which collected data on GI-related biopsies done in Sweden. From these data, 6 target trial emulations were developed, with a separate target trial done for the initiation of each class of medications: angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), statins, proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), and selective serotonin reuptake inhibitors (SSRIs). All participants were followed up every 12 months, to allow for monitoring of symptoms, until MC diagnosis, death, emigration from Sweden, or administrative censoring. Data were reported for a random sample of 10% of all eligible participants. The primary outcome was histologic diagnosis of MC. The target trials had populations of 1,151,816 for ACE-Is versus CCBs, 1,002,567 for ARBs versus CCBs, 2,634,777 for NSAIDs versus non-initiators, 191,482 for PPIs versus non-initiators, 617,064 for SSRIs versus mirtazapine, and 2,604,159 for statins versus non-initiators. In all 6 target trials, the 12-month and 24-month cumulative incidences of MC were less than 0.5%. Estimated risk differences at 12 months were near null for ACE-I versus CCB initiation (0.003 [95% CI, -0.004 to 0.01]), ARB versus CCB initiation (-0.002 [95% CI, -0.01 to 0.004]), NSAID initiation versus non-initiation (0.004 [95% CI, -0.003 to 0.01]), PPI initiation versus non-initiation (0.006 [95% CI, -0.02 to 0.03]), and statin initiation versus non-initiation (0.01 [95% CI, -0.002 to 0.02]). Comparing SSRI versus mirtazapine initiation yielded 12- and 24-month risk differences of 0.04 (95% CI, 0.03 to 0.05) and 0.06 (95% CI, 0.04 to 0.08) percentage points, respectively. In sensitivity analyses examining risk for receiving normal colorectal biopsy results, estimated 12-month risk differences were 0.04 (95% CI, 0.02 to 0.06) percentage points for NSAID initiation versus non-initiation, 0.30 (95% CI, 0.24 to 0.37) for PPI initiation versus non-initiation, and 0.04 (95% CI, 0.01 to 0.08) for SSRIs versus mirtazapine. Overall, this study suggested that the use of potential trigger medications did not significantly affect the risk of MC in older adults.

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