Date Published: November 21, 2017
Publisher: Public Library of Science
Author(s): Tom A. Yates, Laurie A. Tomlinson, Krishnan Bhaskaran, Sinead Langan, Sara Thomas, Liam Smeeth, Ian J. Douglas, John Z. Metcalfe
Abstract: BackgroundRecent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease.Methods and findingsWe studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1–12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3–17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52–0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00–1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00–1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease.ConclusionsIn this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted.
Partial Text: In 2015, there were an estimated 10.4 million incident cases of tuberculosis (TB) globally resulting in approximately 1.4 million deaths . There is little commercial or public investment in TB research and there are only six novel compounds currently in the TB drug development pipeline . In 2015, there were an estimated 480,000 cases of multidrug-resistant TB . Treatment regimens for drug-resistant TB (DRTB) are long and unpleasant, with serious side effects and poor outcomes [1,3,4].
In a large, validated, and nationally representative dataset, we have demonstrated a protective association between lansoprazole use and newly diagnosed TB disease with an adjusted HR of 0.68 (0.52–0.89) when compared with omeprazole or pantoprazole use. This association was not seen in past users of these drugs and no association was seen between lansoprazole use and our negative control outcomes of MI and herpes zoster.