Comparative Effectiveness and Safety of Tiotropium and Olodaterol in Comparison to LABA/ICS

Study Overview
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Brief Summary
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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.

Official Title
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Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids and Long-acting β2 Agonists in COPD Patients

Conditions
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COPD

Intervention / Treatment
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* Drug: Tiotropium bromide + Olodaterol
* Drug: LABA/ICS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019. The first dispensing of either Tio+Olo or LABA/ICS combined inhaler will be defined as the index date. For the main analyses, only fixed dose combination (FDC) inhalers will be included. Sensitivity analyses will also accept free combinations of LABA/ICS. At least one diagnosis of COPD at any time prior to the index date. 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: To increase the likelihood of a true diagnosis of COPD, we will exclude: All patients less than 40 years of age on the index date, and All patients with a diagnosis of asthma in the year prior to the index date 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 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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients initiating Tiotropium+Olodaterol therapy<br> | Drug: Tiotropium bromide + Olodaterol<br>* Tiotropium bromide + Olodaterol<br>|
| Patients initiating Long-acting beta agonist/inhaled corticosteroid therapy<br> | Drug: LABA/ICS<br>* Long-acting beta2-agonist and Inhaled corticosteroids (LABA and ICS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 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). | 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 (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. | From cohort entry (index date) until the 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 | 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. | 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 | 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. | From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry. |