Are Drugs Associated with Microscopic Colitis? A Systematic Review and Meta-Analysis

There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81-3.50, I² 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27-2.96, I² 96.46%), NSAIDs (OR 2.02, 95% CI 1.33-2.70, I² 92.70%) and Statins (OR 1.74, 95% CI 1.19-2.30, I² 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32-5.08, I² 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90-6.19, I² 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54-4.92, I² 98.31%), NSAIDs (OR 3.27, 95% CI 2.06-4.48, I² 95.38%), and Statins (OR 2.23, 95% CI 1.41-3.06, I² 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48-0.88, I² 7.26%), (OR 0.46, 95% CI 0.14-0.78, I² 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49-1.42, I² 37.89%), NSAIDs (OR 1.13, 95% CI 0.49-1.76, I² 59.37%) Statins (OR 0.91, 95% 0.66-1.17, I² 0%) and H2RA (OR 3.48, 95% CI -0.41-7.36, I² 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50-1.72, I² 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group.