Society: AGA

INTRODUCTION: A number of medications have been implicated as primary risk factors for microscopic colitis (MC) and guidelines recommend discontinuation of these medications as part of MC management. However, there are few epidemiologic studies that have attempted to explore a causal relationship between medications and MC.

METHODS: We conducted a cohort study of all residents in Sweden since 2004 over the age of 60 years to examine the association between select medications and the risk of MC. For each medication, new initiators were identified at the time of their first dispensed drug (index date for users) and matched to non-users at the time of dispense of any other medication (index date for non-users) within 6 months of index date for users. Exact 1:1 matching was done according to age, sex, calendar year, healthcare utilization defined by number of prior dispensed medications and encounters for inpatient visits and outpatient subspecialty care, and GI-specific utilizations, including number of endoscopies and GI-related encounters. End of follow up was defined as death, emigration, diagnosis of MC, ascertained through linkage to nationwide histopathology cohort, or December 31^st, 2017, whichever came first. Proportional hazard models were fit to obtain effect estimates. To assess the validity of our models, use of coumadin and beta blockers were defined as negative control exposures while colonoscopy with normal biopsies was defined as a negative control outcome.

RESULTS: We identified 3,278,547 residents of Sweden over the age of 60 years with at least one drug prescription from 2006-2017 which was used to build nine separate cohorts of drug user versus non-users: proton pump inhibitors (PPI, n = 2,487,228), selective serotonin reuptake inhibitors (SSRI, n = 1,232,510), angiotensin converting enzyme inhibitors (ACE-I, n = 2,151,098), angiotensin receptor blockers (n = 1,422,642), Statins (n = 2,374552), NSAIDs (n = 2,581,372), Anti-Parkinson drugs (APD, n = 289,930), coumadin (n = 708,582), and beta blockers (BBs, n = 2,480,988). In an intention-to-treat analysis, PPIs (HR=1.43 [1.32-1.56]), SSRIs (HR= 2.32 [2.07-2.60]), ARBs (HR= 1.26 [1.13-1.42]), and NSAIDs (1.13 [1.06-1.22]) associated with increased risk of MC but equally so with colonoscopy with normal mucosa (Table 1). Our results were similar in as-treated analyses, where participants were censored after discontinuation of medications.

CONCLUSION: In a nationwide cohort study, we observed an increased risk of MC with initiation of previously implicated medications. However, most of these associations were equally observed with receiving a colonoscopy with normal biopsies suggesting that such medication use was associated with undergoing colonoscopy and not MC. These findings suggest that previously observed associations were likely related to surveillance bias.

Sebastian Schneeweiss

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