Association of acid-suppressive therapy and tuberculosis: A causal or coincidental link to the infection?

Background: Acid-suppressant proton-pump inhibitors (PPI) and histamine-2-receptor antagonists (H2RA) are associated with an increased risk of tuberculosis (TB). However, it remains unclear whether this association is causal or coincidental.

Methods: Patients newly diagnosed with TB between 2000 and 2013 were identified from the Taiwan National Health Insurance Database. Each patient with TB was matched in a 1:10 ratio with patients without TB by age, sex, and index date. The time lags from the end of PPI or H2RA treatment to the index date, and respective cumulative doses in the 90 days before the index date, were analyzed for association with TB.

Results: The age (mean [standard deviation] 60.8 [17.3] years) and sex ratio (69.4% males) were comparable between patients with TB (n = 6002) and patients without TB (n = 60,020). Previous PPI or H2RA treatment was more frequently observed in patients with TB (16.6% vs. 8.9%, p < 0.001). Concurrent antacid therapy posed the highest risk for TB (odds ratio [OR] 4.21 for PPI and 2.24 for H2RA, both p < 0.0001), and the closer to the end of the therapy, the more likely TB was detected (p for trend: 0.0077 for PPI and 0.0145 for H2RA). The cumulative doses of antacid in the 90 days before TB had an inverse relationship with TB risk. PPI, used either alone or in combination with H2RA, conferred a higher risk of TB than H2RA alone.

Conclusions: Tuberculosis should be considered in symptomatic patients receiving or recently ceased antacid therapy with PPI or H2RA in TB endemic areas.