COPD
Conditions
Brief summary
The primary objective is to compare the effectiveness of maintenance therapy initiation with the combination treatment Tiotropium and Olodaterol (Olo+Tio) compared with LABA/ICS combination in COPD as the time to the first COPD exacerbation. Secondary objectives are to compare patients treated with Tio+Olo and patients treated with LABA/ ICS combination.
Interventions
Tiotropium bromide + Olodaterol
DRUGLABA/ICS
Long-acting beta2-agonist and Inhaled corticosteroids (LABA and ICS)
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019. 1. The first dispensing of either Tio+Olo or LABA/ICS combined inhaler will be defined as the index date. 2. For the main analyses, only fixed dose combination (FDC) inhalers will be included. Sensitivity analyses will also accept free combinations of LABA/ICS. 2. At least one diagnosis of COPD at any time prior to the index date. 3. At least one year of continuous medical and pharmacy health plan eligibility prior to the index date will be required to allow a baseline period for the covariates and identification of new use of the study drugs.
Exclusion criteria
1. To increase the likelihood of a true diagnosis of COPD, we will exclude: 1. All patients less than 40 years of age on the index date, and 2. All patients with a diagnosis of asthma in the year prior to the index date 2. To limit the population to those without severe lung compromise outside of COPD, we will exclude individuals with lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date 3. To restrict the cohort to new users of Tio+Olo or LABA/ICS, we will exclude any individual with use of either Tio+Olo, LABA/ICS, or LABA/LAMA/ICS combination therapy in free or fixed form for at least one year prior to the index date.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry. | Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of First Hospitalization for Community-acquired Pneumonia | From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry. | Incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. |
| Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy | From cohort entry (index date) until the escalation, up to one year after cohort entry. | Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy, (i.e., addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy). |
| Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy | From cohort entry (index date) until the escalation, up to one year after cohort entry. | Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy. Based on feedback from clinical experts during review of study results, an alternative post-hoc definition was also assessed in which initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination was counted as an outcome. |
| Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy | From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry. | Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (original case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy. |
| Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy | From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry. | Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (alternative case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination. |
Countries
United States
Participant flow
Recruitment details
In this cohort study, administrative data from the HealthCore Integrated Research Database (US, HIRD, Jan 2013 - March 2019) were used to identify and compare new users of Tio+Olo (Tiotropium and Olodaterol) with new users of LABA/ICS (Long-acting Beta2-Agonists/Inhaled Corticosteroids) combination therapy with respect to safety and effectiveness.
Pre-assignment details
Only subjects that met all inclusion and none of the exclusion criteria were included. two cohorts (Initiators of Tiotropium + Olodaterol and patients receiving Long-acting beta agonist / inhaled corticosteroid) were established. The cohorts after propensity score matching were used for the analyses
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium + Olodaterol Cohort of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from administrative data from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol, with the first prescription defined as the index date. Following the index date participants were followed for up to one year. | 2,600 |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy Cohort of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from administrative data from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated long-acting beta agonist / inhaled corticosteroid therapy, with the first prescription defined as the index date. Following the index date participants were followed for up to one year. | 40,353 |
| Total | 42,953 |
Baseline characteristics
| Characteristic | Tiotropium + Olodaterol | Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10.3 | 64.8 years STANDARD_DEVIATION 11.5 | 64.81 years STANDARD_DEVIATION 11.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 1415 Participants | 21994 Participants | 23409 Participants |
| Sex: Female, Male Male | 1185 Participants | 18359 Participants | 19544 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
Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.
Time frame: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 1.63 Events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 2.43 Events per 1,000 Person-days |
Comparison: Cox proportional hazard regression models were used to assess the effect of Tiotropium + Olodaterol combination versus the Long-acting beta agonist / inhaled corticosteroid therapy combination on the risk of a first COPD exacerbation.95% CI: [0.68, 0.85]
Secondary
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy
Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (alternative case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination.
Time frame: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy | 2.16 events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy | 5.67 events per 1,000 Person-days |
Comparison: Cox proportional hazard regression models were used to assess the effect of Tiotropium + Olodaterol combination versus the Long-acting beta agonist / inhaled corticosteroid therapy combination on the risk of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation.95% CI: [0.41, 0.49]
Secondary
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy
Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (original case definition) to triple therapy. Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid. Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy.
Time frame: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy | 2.14 events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy | 5.45 events per 1,000 Person-days |
Comparison: Cox proportional hazard regression models were used to assess the effect of Tiotropium + Olodaterol combination versus the Long-acting beta agonist / inhaled corticosteroid therapy combination on the risk of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation.95% CI: [0.42, 0.51]
Secondary
Incidence Rate of First Hospitalization for Community-acquired Pneumonia
Incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes.
Time frame: From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of First Hospitalization for Community-acquired Pneumonia | 0.23 events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of First Hospitalization for Community-acquired Pneumonia | 0.34 events per 1,000 Person-days |
Comparison: Cox proportional hazard regression models were used to assess the effect of Tiotropium + Olodaterol combination versus the Long-acting beta agonist / inhaled corticosteroid therapy combination on the risk of first hospitalization for community-acquired pneumonia.95% CI: [0.57, 0.97]
Secondary
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy
Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy. Based on feedback from clinical experts during review of study results, an alternative post-hoc definition was also assessed in which initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination was counted as an outcome.
Time frame: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy | 0.57 events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy | 3.14 events per 1,000 Person-days |
Comparison: Cox proportional hazard regression models were used to assess the effect of Tiotropium + Olodaterol combination versus the Long-acting beta agonist / inhaled corticosteroid therapy combination on the risk of escalation.95% CI: [0.19, 0.26]
Secondary
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy
Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy, (i.e., addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy).
Time frame: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Population: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol | Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy | 0.54 events per 1,000 Person-days |
| Long-acting Beta Agonist / Inhaled Corticosteroid Therapy | Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy | 2.90 events per 1,000 Person-days |
95% CI: [0.19, 0.27]