The primary objective of this study is to compare the effectiveness and safety of maintenance treatment of chronic obstructive pulmonary disease (COPD) with the combination of a long-acting muscarinic antagonist, a long-acting beta2-agonist and an inhaled corticosteroid (LAMA-LABA-ICS) compared with the combination of the two bronchodilators (LAMA-LABA). We will conduct a cohort study where first time users of a LAMA-LABA combination (without ICS) or LAMA-LABA-ICS combination will be identified. This cohort will be weighted by fine stratification weights computed using the probability of treatment to create pseudo-population in which the distribution of confounders is balanced. Subjects in the cohort will be followed for up to one year or until the occurrence of death from all-cause, severe COPD exacerbation leading to hospitalisation, and hospitalization for community-acquired pneumonia (serious pneumonia).The weighted Cox proportional hazard model will be used to perform an as-treated analysis that assesses the effect of current use of the LAMA-LABA-ICS combination versus the LAMA-LABA combination on the risk of death and of severe COPD exacerbation, as well as pneumonia. Analysis by blood eosinophil levels, prior exacerbations, history of asthma, as well as different ICS, will be performed to assess the comparative effectiveness in these important subgroups.
The secondary objective is to compare the effectiveness and safety of fluticasone-based triple therapy with budesonide-based triple therapy on these outcomes. This will be done in a similar way, after dividing the LAMA-LABA-ICS initiators according to fluticasone or budesonide.
Using Aurum and GOLD primary care data restricted to linkable HES-APC patients to identify severe exacerbation and hospitalized pneumonia, this study findings should help inform clinical practice guidelines on determining the real world evidence for this important treatment.
The primary outcome event is death of any cause. The secondary outcome is the occurrence of the first severe exacerbation defined by hospitalisation for COPD. The safety outcome is the occurrence of the first severe pneumonia defined by hospitalization for community-acquired pneumonia.
Samy Suissa - Chief Investigator - McGill University
Samy Suissa - Corresponding Applicant - McGill University
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data