Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
To assess the effectiveness of maintenance treatment of Chronic obstructive pulmonary disease (COPD) with the combination of a long-acting bronchodilators (LABA and the long-acting muscarinic antagonists (LAMA) tiotropium (LABA-TIO)) compared with the combination of a LABA and an ICS (LABA-ICS) on the time to COPD exacerbation.
Interventions
DRUGLABA and the LAMA tiotropium (LABA-TIO)
combinational drug
DRUGLABA and an ICS (LABA-ICS)
combinational drug
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 55 Years
Healthy volunteers
No
Inclusion criteria
* New users of long-acting bronchodilators, LABA and tiotropium on the same date or of LABA and ICS, either as a fixed-dose combination or free combination, on the same date between January 2002 and December 2015 * Diagnosis of COPD and age ≥ 55 years
Exclusion criteria
* Less than one year of medical history information prior to the date of combined treatment initiation (cohort entry) * Asthma diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry | 12 Years | The number of observed patients with first COPD exacerbation after cohort entry was reported. The event of time to first COPD exacerbation to occur after cohort entry was defined as a hospitalization for COPD (severe exacerbation) or the prescription of an oral corticosteroid, namely prednisolone (moderate exacerbation) to occur after cohort entry with one-year follow-up, from the as-treated analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of COPD Exacerbations | 12 years | Incidence rates and rate ratios of the moderate or severe exacerbation associated with LABA-TIO relative to LABA-ICS in patients with COPD, with one-year follow-up, from the as-treated analysis, estimated. |
| The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia) | 12 years | The number of the first occurences of the hospitalization for community-acquired pneumonia (serious pneumonia)associated with LABA-TIO relative to LABA-ICS in patients with COPD, with one-year follow-up, from the as-treated analysis and from the time-dependent on-treatment analysis based on current exposure is presented. On-treatment exposure was based on analysis of current use during the entire 1-year follow-up, allowing patients to switch treatments. |
Countries
Canada
Participant flow
Recruitment details
Primary objective was to assess the effectiveness of maintenance treatment of ChronicObstructivePulmonaryDisease (COPD) with combination of Long-acting beta2-agonist(LABA) and the long-acting muscarinic antagonists(LAMA)tiotropium(TIO) compared with the combination of a LABA and an Inhaled corticosteroids(ICS) on the time to COPD exacerbation.
Pre-assignment details
Population-based propensity score-matched incident new-user cohort study.
Participants by arm
| Arm | Count |
|---|---|
| LABA-ICS The patients with COPD who received a Long-acting beta 2-agonist (LABA) and an Inhaled corticosteroids (ICS) (LABA - ICS) prescription on the same day, during follow up. These patients were matched to patients receiving a LABA and a tiotropium on the same day (LABA-TIO) using a time-conditional propensity score-matched approach. | 1,977 |
| LABA-TIO The patients with COPD who received a Long-acting beta 2-agonist (LABA) and tiotropium (TIO) (LABA -TIO) prescription on the same day but no ICS, during follow up. These patients were matched to patients receiving a LABA and an ICS on the same day (LABA-ICS) using a time-conditional propensity score-matched approach. | 1,977 |
| Total | 3,954 |
Baseline characteristics
| Characteristic | LABA-ICS | LABA-TIO | Total |
|---|---|---|---|
| Age, Continuous | 71.8 Years STANDARD_DEVIATION 8.6 | 71.9 Years STANDARD_DEVIATION 8.5 | 71.85 Years STANDARD_DEVIATION 8.55 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 778 Participants | 778 Participants | 1556 Participants |
| Sex: Female, Male Male | 1199 Participants | 1199 Participants | 2398 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
The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry
The number of observed patients with first COPD exacerbation after cohort entry was reported. The event of time to first COPD exacerbation to occur after cohort entry was defined as a hospitalization for COPD (severe exacerbation) or the prescription of an oral corticosteroid, namely prednisolone (moderate exacerbation) to occur after cohort entry with one-year follow-up, from the as-treated analysis.
Time frame: 12 Years
Population: The main analysis was on matched patients. The patients with LABA-TIO initiators were matched with initiators of LABA-ICS using a time-conditional propensity score-matched approach.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LABA-ICS | The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry | Moderate/severe exacerbation | 344 Participants |
| LABA-ICS | The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry | Severe exacerbation | 55 Participants |
| LABA-TIO | The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry | Moderate/severe exacerbation | 412 Participants |
| LABA-TIO | The Number of Observed Patients With First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation to Occur After Cohort Entry | Severe exacerbation | 60 Participants |
Comparison: The Cox proportional hazard regression model was used to perform for moderate/severe exacerbation that assesses the effect of current use of LABA-TIO combination versus the LABA-ICS combination on the risk of a first COPD exacerbation.95% CI: [0.9, 1.2]Cox proportional hazards model
Comparison: The Cox proportional hazard regression model was used to perform for severe exacerbation that assesses the effect of current use of LABA-TIO combination versus the LABA-ICS combination on the risk of a first COPD exacerbation.95% CI: [0.65, 1.36]Cox proportional hazards model
Secondary
The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia)
The number of the first occurences of the hospitalization for community-acquired pneumonia (serious pneumonia)associated with LABA-TIO relative to LABA-ICS in patients with COPD, with one-year follow-up, from the as-treated analysis and from the time-dependent on-treatment analysis based on current exposure is presented. On-treatment exposure was based on analysis of current use during the entire 1-year follow-up, allowing patients to switch treatments.
Time frame: 12 years
Population: The main analysis was on matched patients. The patients with LABA-TIO initiators were matched with initiators of LABA-ICS using a time-conditional propensity score-matched approach.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LABA-ICS | The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia) | As-treated analysis | 41 Hospitalizations |
| LABA-ICS | The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia) | On-treatment exposure | 143 Hospitalizations |
| LABA-TIO | The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia) | As-treated analysis | 32 Hospitalizations |
| LABA-TIO | The Occurrence of the First Hospitalization for Community-acquired Pneumonia (Serious Pneumonia) | On-treatment exposure | 49 Hospitalizations |
Comparison: The cox proportional hazard regression model was used to perform an as-treated analysis that assesses the effect of current use of LABA-TIO combination versus the LABA-ICS combination on the risk of a first COPD exacerbation.95% CI: [0.42, 1.05]Cox proportional hazards model
Comparison: The Cox proportional hazard regression model was used to perform an on-treatment analysis that assesses the effect of current use of LABA-TIO combination versus the LABA-ICS combination on the risk of a first COPD exacerbation.95% CI: [0.48, 0.92]Cox proportional hazards model
Secondary
The Rate of COPD Exacerbations
Incidence rates and rate ratios of the moderate or severe exacerbation associated with LABA-TIO relative to LABA-ICS in patients with COPD, with one-year follow-up, from the as-treated analysis, estimated.
Time frame: 12 years
Population: The main analysis was on matched patients. The patients with LABA-TIO initiators were matched with initiators of LABA-ICS using a time-conditional propensity score-matched approach.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LABA-ICS | The Rate of COPD Exacerbations | Moderate/severe exacerbation | 0.83 Events per participant-year |
| LABA-ICS | The Rate of COPD Exacerbations | Severe exacerbation | 0.13 Events per participant-year |
| LABA-TIO | The Rate of COPD Exacerbations | Moderate/severe exacerbation | 0.91 Events per participant-year |
| LABA-TIO | The Rate of COPD Exacerbations | Severe exacerbation | 0.11 Events per participant-year |
Comparison: Moderate/severe exacerbation95% CI: [0.92, 1.25]Negative binomial model
Comparison: Severe exacerbation95% CI: [0.55, 1.33]Negative binomial model