Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by increasing breathlessness. It is a major cause of disability, it reduces quality of life and is one of the leading causes of death. An acute exacerbation of COPD can occur when there is a sudden worsening of usual COPD symptoms such as increase wheezing and shortness of breath, as well as presence of persistent cough. Severe exacerbations require hospitalisation.
Several treatments can be prescribed to improve COPD symptoms. Typically, it involves medication called bronchodilators. This class of drug helps to reduce shortness of breath by opening the airways and makes it easier to breath. However, the relief of symptoms often involves the addition of a different type of medicines such as the combination of one or two long-acting bronchodilators or with an inhaled corticosteroid. Recently, the combination of all three has been introduced. The objective of the study is to compare the effectiveness and safety of these different combinations in preventing exacerbations and mortality.
The findings of this study should provide useful evidence on the benefits and risks of these newer treatment in the context of real-world clinical practice and help inform clinical guidelines.
The primary objective of this study is to compare the effectiveness and safety of chronic obstructive pulmonary disease (COPD) treatment with the single-inhaler combination of a long-acting muscarinic antagonist (LAMA), a long-acting beta2-agonist (LABA), and an inhaled corticosteroid (ICS; LAMA-LABA-ICS) with combinations of LABA-ICS and LAMA-LABA. The secondary objective is to compare combinations of LAMA-LABA with LABA-ICS and with LAMA monotherapy.
The source population will include all patients with a COPD diagnosis in 1995-2023, at least 40 years of age at diagnosis, who subsequently received these therapies after September 2013, when LAMA-LABA became available in the UK.. A cohort study will compare first-time users of a single-inhaler combination of LABA-ICS, of LAMA-LABA or LAMA-LABA-ICS after 15 September 2017, when triple inhalers were available, after adjusting by fine stratification weights using propensity scores to balance the confounders. Subjects will be followed for up to one year, until the occurrence of an exacerbation, moderate or severe, death , or hospitalization for community-acquired pneumonia. The weighted Cox proportional hazard model will be used to compare, as-treated, LAMA-LABA-ICS with LAMA-LABA and LABA-ICS on the risk of these outcomes, also stratified by blood eosinophil levels, prior exacerbations, and history of asthma.
The same techniques will be used to conduct a cohort study where first-time users of LABA-ICS, LAMA-LABA, or LAMA monotherapy, after 1 September 2013, will be compared on the same outcomes.
The tertiary objective is to compare the effectiveness and safety of fluticasone-based triple therapy with budesonide-based triple therapy on these outcomes.
Using the Aurum primary care data restricted to linkable HES-APC patients to identify severe exacerbation and hospitalized pneumonia, the findings of this study should provide useful evidence on the benefits and risks of these newer treatment in the context of real-world clinical practice and help inform clinical guidelines.
The primary outcome events are occurrence of the first moderate or severe exacerbation, occurrence of the first severe exacerbation defined by hospitalisation for COPD, and death from all-cause. The safety outcome is the occurrence of the first severe pneumonia defined by hospitalization for community-acquired pneumonia.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care