Medication-induced microscopic colitis: Do recency and duration of use matter?

Abstract

Background: Microscopic colitis (MC) is a colonic disorder characterised by chronic watery diarrhoea. There is increasing evidence (table present) that exposure to commonly prescribed drugs like non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), and statins is associated with an increased risk of MC. However, the attributive risk of recent or longer use and the effect of higher dosages has never been investigated, although this information would give more insight in the possible mechanism of medication-induced MC. Methods: A case-control study was conducted using the British Clinical Practice Research Datalink. Cases were diagnosed with microscopic, lymphocytic (LC) or collagenous (CC) colitis between 1992-2013. For each case, up to 5 randomly selected controls without MC were matched by year of birth, gender, and practice. The index date of the case defined that of the controls. Prescriptions within 60 days prior to index date were excluded to take into account a latency (lag) time and to minimize reverse causality. Exposure status was classified as current (61-90 days), recent (91-150 days), and past use (>150 days) according to the time since most recent prescription prior to index date. In current users, duration of continuous use and average daily dose was assessed. Conditional logistic regression analysis was applied to quantify the strength of the associations and to correct for confounders. Results: In total, 1.211 cases with MC (394 CC, 292 LC, 525 undefined MC) and 6.041 controls were identified. Current use of NSAIDs (OR 1.79, 95% CI 1.36-2.36), PPIs (OR 3.93, 95% CI 2.25-4.74), and SSRIs (OR 2.27, 95% CI 1.79-2.89) was associated with an increased risk of MC compared to never and past use. Especially a 4-12 months continuous use of NSAIDs, PPIs, and SSRIs increased the risk of MC. Long-term use (>24 months) attenuated this risk. Exposure to more than 1.25 standardised daily dosages was associated with an elevated risk of MC in PPI (OR 6.90, 95% CI 3.82-12.49) and SSRI users (OR 4.15, 95% CI 2.47-6.97). Analysis per MC subtype showed a positive association between current use of NSAIDs (OR 2.28, 95% CI 1.46-3.54) and PPIs (OR 6.15, 95% CI 4.41-8.58) in CC and current use of PPIs (OR 2.40, 95% CI 1.60-3.59) and SSRIs (OR 2.65, 95% CI 1.69-4.15) in LC. Statin use was not associated with MC. A sensitivity analysis with a lag time of 90 days showed conclusions consistent with the primary analysis. Conclusions: Use of NSAIDs, PPIs, and SSRIs is associated with an increased risk of MC. Especially in current users with a continuous exposure duration of 4 to 12 months, drug exposure as cause for MC should be considered.