Chronic obstructive pulmonary disease (COPD) has become the third leading cause of death worldwide. Long-acting beta2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs) and inhaled corticosteroids (ICS) are central pharmacologic therapies for COPD. ICS are associated with some known risks, including pneumonia, while their effectiveness appears to vary with different patient characteristics, including blood eosinophil counts, asthma, frequent exacerbations and smoking. We propose to determine the optimal initial and subsequent treatment strategy for COPD, balancing effectiveness and risk, according to specific patient characteristics.
We will use a large cohort of patients newly treated for COPD to uncover patient characteristics of differential effects of treatment on the incidence of COPD exacerbations and pneumonia. The cohort, extracted from the CPRD, will include new users of LAMA, LABA or LABA-ICS inhalers during 2002-2018, age 40 or over, followed for two years for the endpoints of COPD exacerbation and pneumonia. It is estimated to include over 150,000 subjects. We will conduct a two-stage dynamic treatment regime (DTR) analysis, using the recursive approach to dynamic weighted survival modelling, to determine patient-treatment profiles that maximize the time to the second COPD exacerbation and to severe pneumonia. At each stage, propensity scores will be used to weigh the analyses by inverse probability of treatment and of censoring. The DTR analysis will estimate blip functions on several tailoring covariates, namely blood eosinophils, smoking, sex, exacerbation history, asthma diagnosis, as well as age, obesity and dyspnea severity.
This large study in a real world setting of the treatment of COPD, using the dynamic treatment regime approach, will provide a precision medicine algorithm to optimize COPD management. By using patient characteristics routinely measured in the typical clinical setting, clinicians will be able to choose optimal treatments according to clinical profiles that increase the effectiveness and reduce the risk of treatment.
Moderate and/or severe exacerbation of COPD (prescription for an oral corticosteroid (prednisolone) and/or hospitalization with a primary diagnosis of COPD); hospitalization for community-acquired pneumonia.
Samy Suissa - Chief Investigator - McGill University
Samy Suissa - Corresponding Applicant - McGill University
Michael Wallace - Collaborator - University Of Waterloo
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University