Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
To assess the effectiveness of maintenance treatment of Chronic obstructive pulmonary disease (COPD) with the Long-acting beta2-agonist - long-acting muscarinic antagonists-inhaled corticosteroids (LABA-LAMA-ICS) combination with a LABA-LAMA combination on the risk of COPD exacerbation and the safety on the incidence of community acquired pneumonia.
Interventions
DRUGLong-acting beta2-agonist-long-acting muscarinic antagonists-inhaled corticosteroids(LABA-LAMA-ICS)
(LABA-LAMA-ICS)
DRUGLong-acting beta2-agonist-inhaled corticosteroids-long-acting muscarinic antagonists (LABA-LAMA)
(LABA-LAMA)
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* New users of long-acting bronchodilators, Long-acting beta2-agonist (LABA) and long-acting muscarinic antagonists (LAMA) on the same date or of LABA, LAMA and inhaled corticosteroids (ICS), either as a fixed-dose combination (LABA-ICS) or free combination, on the same date between January 2002 and December 2016. * Diagnosis of Chronic obstructive pulmonary disease (COPD) prior to first maintenance inhaler and age ≥ 55 years at first maintenance inhaler.
Exclusion criteria
* Less than one year of medical history information prior to the date of combined treatment initiation (study cohort entry) * Asthma diagnosis prior to study cohort entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Hospitalised With Severe Exacerbation | 1 year | The primary outcome event for effectiveness was the first COPD exacerbation to occur after cohort entry. The event was defined as a hospitalization with a primary diagnosis of COPD (severe exacerbation) is presented. |
| Number of Participants Hospitalised With Moderate Exacerbation | 1 year | The primary outcome event for effectiveness was the first COPD exacerbation to occur after cohort entry. The event was defined as a hospitalization with the prescription of an oral corticosteroid, namely prednisolone (moderate exacerbation) is presented. |
| Number of Participants Hospitalised With Community-acquired Pneumonia (Serious Pneumonia) | 1 year | The primary outcome event for safety was the occurrence of the first hospitalization for community-acquired pneumonia (serious pneumonia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of COPD Exacerbations Over the One-year Follow-up | 1 year | This outcome was based on the number of hospitalizations and on the number of courses of treatment with an oral corticosteroid. A gap of at least 30 days between treatment courses was required to consider the exacerbations as separate events. |
Countries
United Kingdom
Participant flow
Recruitment details
Base cohort consisted participants with ChronicObstructivePulmonaryDisease(COPD) who subsequently received at least one prescription for a long-acting bronchodilator, either Long-Acting Beta2-Agonist(LABA) or long-acting MuscarinicAntagonists(LAMA), or for inhaled corticosteroid(ICS), alone or in combination, from 1January2002 until 31December2015.
Pre-assignment details
Population-based incident new-user cohort design with high-dimensional time-conditional propensity score matching. The study cohort was formed from the base cohort using an incident new-user cohort design with time-conditional propensity scores.
Participants by arm
| Arm | Count |
|---|---|
| LABA-LAMA-ICS The participants with COPD initiating treatment with LABA-LAMA-ICS combination as three or two inhalers on the same day were included in this group. Participants were followed for up to one year from the cohort entry date, the date of death, 31 March 2016, or the end of coverage in the practice, whichever occurred first. | 6,921 |
| LABA-LAMA The participants with COPD with their first concurrent prescriptions of a LAMA and LABA (no ICS) as two inhalers on the same day included in this group were matched on high-dimensional propensity score with patients initiating treatment with LABA-LAMA-ICS combination as three or two inhalers on the same day. Participants were followed for up to one year from the cohort entry date, the date of death, 31 March 2016, or the end of coverage in the practice, whichever occurred first. | 1,932 |
| Total | 8,853 |
Baseline characteristics
| Characteristic | LABA-LAMA-ICS | LABA-LAMA | Total |
|---|---|---|---|
| Age, Continuous | 71.9 Years STANDARD_DEVIATION 8.5 | 71.6 Years STANDARD_DEVIATION 8.5 | 71.8 Years STANDARD_DEVIATION 8.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 2619 Participants | 746 Participants | 3365 Participants |
| Sex: Female, Male Male | 4302 Participants | 1186 Participants | 5488 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants Hospitalised With Community-acquired Pneumonia (Serious Pneumonia)
The primary outcome event for safety was the occurrence of the first hospitalization for community-acquired pneumonia (serious pneumonia).
Time frame: 1 year
Population: The main analysis was on matched patients. The cohort of initiators of LAMA-LABA-ICS and their propensity score-matched initiators of LAMA-LABA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LABA-LAMA-ICS | Number of Participants Hospitalised With Community-acquired Pneumonia (Serious Pneumonia) | 3099 Participants |
| LABA-LAMA | Number of Participants Hospitalised With Community-acquired Pneumonia (Serious Pneumonia) | 634 Participants |
95% CI: [1.03, 2.07]Regression, Cox
Primary
Number of Participants Hospitalised With Moderate Exacerbation
The primary outcome event for effectiveness was the first COPD exacerbation to occur after cohort entry. The event was defined as a hospitalization with the prescription of an oral corticosteroid, namely prednisolone (moderate exacerbation) is presented.
Time frame: 1 year
Population: The main analysis was on matched patients. The cohort of initiators of LAMA-LABA-ICS and their propensity score-matched initiators of LAMA-LABA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LABA-LAMA-ICS | Number of Participants Hospitalised With Moderate Exacerbation | 2487 Participants |
| LABA-LAMA | Number of Participants Hospitalised With Moderate Exacerbation | 542 Participants |
95% CI: [0.87, 1.09]Regression, Cox
Primary
Number of Participants Hospitalised With Severe Exacerbation
The primary outcome event for effectiveness was the first COPD exacerbation to occur after cohort entry. The event was defined as a hospitalization with a primary diagnosis of COPD (severe exacerbation) is presented.
Time frame: 1 year
Population: The main analysis was on matched patients. The cohort of initiators of LAMA-LABA-ICS and their propensity score-matched initiators of LAMA-LABA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LABA-LAMA-ICS | Number of Participants Hospitalised With Severe Exacerbation | 3074 Participants |
| LABA-LAMA | Number of Participants Hospitalised With Severe Exacerbation | 630 Participants |
95% CI: [0.79, 1.38]Regression, Cox
Secondary
The Rate of COPD Exacerbations Over the One-year Follow-up
This outcome was based on the number of hospitalizations and on the number of courses of treatment with an oral corticosteroid. A gap of at least 30 days between treatment courses was required to consider the exacerbations as separate events.
Time frame: 1 year
Population: The main analysis was on matched patients. The cohort of initiators of LAMA-LABA-ICS and their propensity score-matched initiators of LAMA-LABA.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LABA-LAMA-ICS | The Rate of COPD Exacerbations Over the One-year Follow-up | Moderate/ sever exacerbation | 94.4 exacerbations per 100 person year |
| LABA-LAMA-ICS | The Rate of COPD Exacerbations Over the One-year Follow-up | Severe exacerbation | 13.4 exacerbations per 100 person year |
| LABA-LAMA | The Rate of COPD Exacerbations Over the One-year Follow-up | Moderate/ sever exacerbation | 89.3 exacerbations per 100 person year |
| LABA-LAMA | The Rate of COPD Exacerbations Over the One-year Follow-up | Severe exacerbation | 11.0 exacerbations per 100 person year |
Comparison: Moderate/ sever exacerbation95% CI: [0.83, 1.04]Negative binomial regression model
Comparison: Severe exacerbation95% CI: [0.7, 1.28]Negative binomial regression model