Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort

Autor: Yates, Tom A., Tomlinson, Laurie A., Bhaskaran, Krishnan, Langan, Sinead, Thomas, Sara, Smeeth, Liam, Douglas, Ian J.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS Medicine
PLoS Medicine, Vol 14, Iss 11, p e1002457 (2017)
ISSN: 1549-1676
1549-1277
Popis: Background Recent 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 findings We 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. Conclusions In 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.
Ian Douglas and colleagues report lower incidence of TB disease in users of the proton pump inhibitor lansoprazole using data from a large UK cohort study.
Author summary Why was this study done? A recent report describes preclinical laboratory findings showing lansoprazole has strong activity against M. tuberculosis, including drug-resistant strains. Other proton pump inhibitors, omeprazole and pantoprazole had no such activity. No clinical investigations of this possible protective association with lansoprazole have yet been reported. What did the researchers do and find? We 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 tuberculosis disease than omeprazole or pantoprazole users. Comparing 527,364 lansoprazole initiators with 923,500 omeprazole or pantoprazole initiators, lansoprazole users had a lower rate of TB disease with an adjusted HR of 0.68 (0.52–0.89). No association was found with negative control outcomes; myocardial infarction (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). What do these findings mean? In vitro, animal, and, now, clinical epidemiological data, all suggest that lansoprazole has activity against M. tuberculosis. Pharmacodynamic and early phase clinical trials are warranted to assess whether lansoprazole, or its metabolites, might have a role in the prevention or treatment of M. tuberculosis infection or tuberculosis disease.
Databáze: OpenAIRE
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