Tuberculosis (TB) disease is a serious global health threat claiming millions of lives every year. Although curable, resistance of Mycobacterium bacteria to antibiotics may develop. In addition, prolonged duration of treatment, drug toxicity and presence of other medical conditions increase the likelihood of poor treatment outcomes. To address these concerns, novel treatment strategies are currently being developed, with research shifting its focus towards selecting potential adjuvant therapies to antibiotics. A strong candidate that gains considerable traction in the recent years is statin, a drug that is widely prescribed for the prevention of cardiovascular events. Statins have been found to influence immunity and improve the antimicrobial activity of anti-TB drugs in animal studies. However, the effectiveness of a combination therapy of antibiotics and statins in patients is currently unknown. Thus, we aim to assess the potential use of statin as an adjunctive therapy by examining the relationship between statin use and treatment outcomes of patients receiving standard therapy for TB disease. Findings from this study will provide valuable information on the potential benefits of statins against active TB and could help guide the development of new therapeutic interventions.
Statins are a class of drugs that lowers the level of host cholesterol by blocking 3-hydroxy-3-methylgluratyl coenzyme A reductase, the rate-limiting enzyme of the cholesterol synthesis pathway. Given their cost-effectiveness and relative safety, statins are widely prescribed for primary and secondary prevention of cardiovascular events. Interestingly, accumulating evidence reveals many other effects of statins beyond lipid lowering, such as immunomodulation and anti-inflammation that can enhance clearance of infectious pathogens including dengue virus, Salmonella enterica, and Chlamydia pneumonia. More recently, studies have shown that statins can also improve the immune response against Mycobacterium tuberculosis (Mtb) in mice and lower the incidence of active tuberculosis (TB) in humans. This has led to the proposal of repurposing statins as therapeutic agents against TB disease and more specifically as adjuncts to the first-line therapy. Thus, the objective of our study is to investigate the association between statins and treatment outcomes in adult patients receiving first-line therapy for TB disease using data from the United Kingdom Clinical Research Datalink (UK CPRD) and the Hospital Episodes Statistics (HES) inpatient databases. In this retrospective cohort study, we will compare statin users with matched comparators (non-users and active comparators) and assess their risk of patient outcomes, including TB death, treatment completion, cure and TB relapse, using Cox proportional hazard regression. Findings of the study will provide evidence for the use of statins as adjuvant therapy to TB disease and thereby opening new avenues for TB intervention.
TB death; TB treatment completion; TB cure; TB relapse.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Paul Brassard - Corresponding Applicant - McGill University
Pierre Ernst - Collaborator - McGill University
Zharmaine Ante - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation