Trial Outcomes & Findings for A Study in South Korea Using Medical Records to Look at Different Treatments for Chronic Obstructive Airway Disease (COPD) (NCT NCT04172701)

NCT ID: NCT04172701

Last Updated: 2022-04-07

Results Overview

Pneumonia was defined as ≥1 inpatient or outpatient claims 1) with ICD-10 codes for pneumonia recorded as any diagnosis in inpatient claims or primary \~ 4th secondary diagnosis in outpatient claims, AND 2) with diagnostic test code for chest-X ray or chest- computed tomography (CT), AND 3) with antibiotics prescription during the following period after the index date. To assess the incidence of pneumonia event, the first pneumonia event observed during the follow-up period was considered. Incidence rate for the first pneumonia event was calculated as below: Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

• Recruitment status: COMPLETED
• Target enrollment: 9284 participants
• Primary outcome timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.
• Results posted on: 2022-04-07

Participant Flow

This study was a retrospective, observational, non-interventional cohort study using national health insurance claims data from the National Health Insurance Service (NHIS) of South Korea to compare the real-world outcomes among chronic obstructive pulmonary disease (COPD) patients initiating long-acting muscarinic antagonists (LAMA) or inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) in South Korea.

Only subjects that met all inclusion and none of the exclusion criteria were included.

Participant milestones

Measure	LAMA Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Overall Study STARTED	6352	2932
Overall Study Propensity Score (PS) Matched Population	2444	2444
Overall Study COMPLETED	6352	2932
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.	Total n=4888 Participants Total of all reporting groups
Age, Continuous	69.57 Years STANDARD_DEVIATION 7.85 • n=2444 Participants	69.73 Years STANDARD_DEVIATION 7.91 • n=2444 Participants	69.65 Years STANDARD_DEVIATION 7.88 • n=4888 Participants
Sex: Female, Male Female	590 Participants n=2444 Participants	622 Participants n=2444 Participants	1212 Participants n=4888 Participants
Sex: Female, Male Male	1854 Participants n=2444 Participants	1822 Participants n=2444 Participants	3676 Participants n=4888 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Pneumonia was defined as ≥1 inpatient or outpatient claims 1) with ICD-10 codes for pneumonia recorded as any diagnosis in inpatient claims or primary ~ 4th secondary diagnosis in outpatient claims, AND 2) with diagnostic test code for chest-X ray or chest- computed tomography (CT), AND 3) with antibiotics prescription during the following period after the index date. To assess the incidence of pneumonia event, the first pneumonia event observed during the follow-up period was considered.

Incidence rate for the first pneumonia event was calculated as below:

Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate for the First Pneumonia Event	109.82 patients/1000 person-years	167.10 patients/1000 person-years

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Pneumonia was defined as ≥1 inpatient or outpatient claims 1) with ICD-10 codes for pneumonia recorded as any diagnosis in inpatient claims or primary ~ 4th secondary diagnosis in outpatient claims, AND 2) with diagnostic test code for chest-X ray or chest- computed tomography (CT), AND 3) with antibiotics prescription during the following period after the index date.

This outcome measure reports: Total number of pneumonia events/ sum of follow-up duration (person-years) for all participants

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Pneumonia Events	182.51 events/1000 person-years	264.99 events/1000 person-years

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Pneumonia was defined as ≥1 inpatient or outpatient claims 1) with ICD-10 codes for pneumonia recorded as any diagnosis in inpatient claims or primary ~ 4th secondary diagnosis in outpatient claims, AND 2) with diagnostic test code for chest-X ray or chest- computed tomography (CT), AND 3) with antibiotics prescription during the following period after the index date. Date of pneumonia event was defined as the starting date of outpatient claim, or as the admission date of inpatient claim with the above 3 conditions to define pneumonia event.

Mean and Standard Deviation of time to first pneumonia event from the index date was estimated using the Kaplan-Meier curve.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to First Pneumonia Event From the Index Date	544.96 days Standard Deviation 609.83	413.35 days Standard Deviation 475.8

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Pneumonia was defined as ≥1 inpatient or outpatient claims 1) with ICD-10 codes for pneumonia recorded as any diagnosis in inpatient claims or primary ~ 4th secondary diagnosis in outpatient claims, AND 2) with diagnostic test code for chest-X ray or chest- computed tomography (CT), AND 3) with antibiotics prescription during the following period after the index date.

Number of patients with pneumonia event is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With Pneumonia Event	501 Participants	605 Participants

PRIMARY outcome

Timeframe: Up to 12 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

To assess the incidence of COPD exacerbation event (all types), the first COPD exacerbation event among pre-defined moderate COPD exacerbation and severe COPD exacerbation event observed within the 12-month period after the index date was considered.

Moderate COPD exacerbation was defined as ≥ 1 outpatient claims 1) with ICD-10 codes for COPD recorded as primary ~ 4th secondary diagnosis, AND 2) with systemic steroids and/or antibiotics prescription within 12 months after the index date. Severe COPD exacerbation was defined as ≥ 1 Emergency Room (ER) visit or inpatient claims 1) with ICD-10 codes for COPD or diseases due to COPD worsening as any diagnosis, AND 2) with systemic steroids and/or antibiotics prescription.

Incidence rate of COPD exacerbation events (all types) was calculated as below: Incidence rate per 1000 person-years= Number of patients with event/sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of the First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Event (All Types)	714.18 patients/1000 person-years	827.77 patients/1000 person-years

PRIMARY outcome

Timeframe: Up to 12 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

To assess the frequency of all types (moderate and severe) COPD exacerbation events, any events observed within the 12-month period after the index date was considered.

Moderate COPD exacerbation was defined as ≥ 1 outpatient claims 1) with ICD-10 codes for COPD recorded as primary ~ 4th secondary diagnosis, AND 2) with systemic steroids and/or antibiotics prescription within 12 months after the index date. Severe COPD exacerbation was defined as ≥ 1 Emergency Room (ER) visit or inpatient claims 1) with ICD-10 codes for COPD or diseases due to COPD worsening as any diagnosis, AND 2) with systemic steroids and/or antibiotics prescription.

Outcome measure reports: Total number of COPD exacerbation events (all types)/sum of follow-up duration (person-years) for all participants

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Events (All Types)	1357.48 events/1000 person-years	1523.68 events/1000 person-years

PRIMARY outcome

Timeframe: Up to 12 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Number of patients with Chronic Obstructive Pulmonary Disease (COPD) exacerbation (moderate or severe) events is reported.

Moderate COPD exacerbation was defined as ≥ 1 outpatient claims 1) with ICD-10 codes for COPD recorded as primary ~ 4th secondary diagnosis, AND 2) with systemic steroids and/or antibiotics prescription within 12 months after the index date. Severe COPD exacerbation was defined as ≥ 1 Emergency Room (ER) visit or inpatient claims 1) with ICD-10 codes for COPD or diseases due to COPD worsening as any diagnosis, AND 2) with systemic steroids and/or antibiotics prescription.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Events	1170 Participants	1285 Participants

PRIMARY outcome

Timeframe: Up to 12 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of time to first COPD exacerbation (moderate or severe) event from the index date was estimated using the Kaplan-Meier curve.

Moderate COPD exacerbation was defined as ≥ 1 outpatient claims 1) with ICD-10 codes for COPD recorded as primary ~ 4th secondary diagnosis, AND 2) with systemic steroids and/or antibiotics prescription within 12 months after the index date. Severe COPD exacerbation was defined as ≥ 1 Emergency Room (ER) visit or inpatient claims 1) with ICD-10 codes for COPD or diseases due to COPD worsening as any diagnosis, AND 2) with systemic steroids and/or antibiotics prescription. Date of severe COPD exacerbation event was defined as the starting date of ER claims or admission date of inpatient claims with the above 2 conditions to define moderate COPD exacerbation event.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Event From the Index Date	113.94 days Standard Deviation 106.08	111.92 days Standard Deviation 105.04

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

To assess the incidence rate of initiating triple combination therapy, the first triple combination therapy observed during the follow-up period was considered.

Triple combination therapy of inhaled corticosteroids (ICS), long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA) was defined as ≥ 1 outpatient or inpatient claims with a combination of ICS, LABA, and LAMA. Three components of ICS, LABA and LAMA MUST have been prescribed together in a same prescription issued on same date to be considered as triple combination therapy (i.e. ICS/LABA fixed dose combination (FDC) and LAMA, ICS and LABA/LAMA FDC, ICS/LABA FDC and LABA/LAMA FDC, ICS and LABA and LAMA are all considered as triple combination therapy).

Incidence rate of initiating triple combination therapy is reported as: Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Initiating Triple Combination Therapy	80.98 patients/1000 person-years	139.82 patients/1000 person-years

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Number of patients who initiated a triple combination therapy is reported. Triple combination therapy of inhaled corticosteroids (ICS), long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA) was defined as ≥ 1 outpatient or inpatient claims with a combination of ICS, LABA, and LAMA. Three components of ICS, LABA and LAMA MUST have been prescribed together in a same prescription issued on same date to be considered as triple combination therapy (i.e. ICS/LABA fixed dose combination (FDC) and LAMA, ICS and LABA/LAMA FDC, ICS/LABA FDC and LABA/LAMA FDC, ICS and LABA and LAMA are all considered as triple combination therapy).

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients Who Initiated a Triple Combination Therapy	383 Participants	518 Participants

PRIMARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Median and Inter-Quartile Range of time to initiating triple combination therapy from the index date was estimated using the Kaplan-Meier curve.

Triple combination therapy of inhaled corticosteroids (ICS), long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA) was defined as ≥ 1 outpatient or inpatient claims with a combination of ICS, LABA, and LAMA. Three components of ICS, LABA and LAMA MUST have been prescribed together in a same prescription issued on same date to be considered as triple combination therapy (i.e. ICS/LABA fixed dose combination (FDC) and LAMA, ICS and LABA/LAMA FDC, ICS/LABA FDC and LABA/LAMA FDC, ICS and LABA and LAMA are all considered as triple combination therapy).

Date of triple combination therapy was defined as the starting date of outpatient claim or admission date of inpatient claim with a combination of ICS/LABA and LAMA.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to Initiating Triple Combination Therapy From the Index Date	281 days Interval 92.0 to 606.0	207 days Interval 99.0 to 394.0

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of any medical visit per person per month is reported. Medical visits were calculated as the sum of inpatient and outpatient visits assuming that emergency room (ER) visits, intensive care unit (ICU) visits and visit for pharmacy dispensation would be counted with the inclusion of inpatient and outpatient visit.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Resource Utilization (HCRU): Number of Any Medical Visit (Per Person Per Month)	2.81 visits per person per month Standard Deviation 2.30	2.73 visits per person per month Standard Deviation 1.93

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of outpatient visits per person per month is reported. Outpatient visit was defined as clinic, hospital, or other medical institution (e.g. public health, etc.) visit as an outpatient.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Resource Utilization (HCRU): Number of Outpatient Visits (Per Person Per Month)	2.75 visits per person per month Standard Deviation 2.29	2.66 visits per person per month Standard Deviation 1.92

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of inpatient visits per person per month is reported. Inpatient visit was defined as at least 1 overnight stay in a hospital as an inpatient.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Resource Utilization (HCRU): Number of Inpatient Visits (Per Person Per Month)	0.06 visits per person per month Standard Deviation 0.10	0.07 visits per person per month Standard Deviation 0.13

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of ER visits per person per month is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Resource Utilization (HCRU): Number of Emergency Room (ER) Visits (Per Person Per Month)	0.03 visits per person per month Standard Deviation 0.08	0.04 visits per person per month Standard Deviation 0.09

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of ICU visits per person per month is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Resource Utilization (HCRU): Number of Intensive Care Unit (ICU) Visits (Per Person Per Month)	0.00 visits per person per month Standard Deviation 0.02	0.01 visits per person per month Standard Deviation 0.02

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

COPD-related HCRU was defined as medical claims with ICD-10 codes for COPD and/or COPD-related diseases. Mean and Standard Deviation of any medical visit (inpatient and outpatient visits which include emergency room (ER) and intensive care unit (ICU) visits) per person per month is reported. For outpatient claims, COPD-related HCRU was defined as claims with ICD-10 codes for COPD as primary ~ 4th secondary diagnosis. For inpatient claims, COPD-related HCRU was defined as claims with ICD-10 codes for COPD and/or for diseases due to COPD worsening as any diagnosis.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Resource Utilization (HCRU): Number of Any Medical Visit (Per Person Per Month)	0.66 visits per person per month Standard Deviation 0.39	0.60 visits per person per month Standard Deviation 0.47

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of outpatient visits per person per month is reported. For outpatient claims, COPD-related HCRU was defined as claims with ICD-10 codes for COPD as primary ~ 4th secondary diagnosis.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Resource Utilization (HCRU): Number of Outpatient Visits (Per Person Per Month)	0.63 visits per person per month Standard Deviation 0.38	0.56 visits per person per month Standard Deviation 0.46

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of inpatient visits per person per month is reported. For inpatient claims, COPD-related HCRU was defined as claims with ICD-10 codes for COPD and/or for diseases due to COPD worsening as any diagnosis.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Resource Utilization (HCRU): Number of Inpatient Visits (Per Person Per Month)	0.03 visits per person per month Standard Deviation 0.07	0.03 visits per person per month Standard Deviation 0.10

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of ER visits per person per month is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Resource Utilization (HCRU): Number of Emergency Room (ER) (Visits Per Person Per Month)	0.01 visits per person per month Standard Deviation 0.03	0.01 visits per person per month Standard Deviation 0.05

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of ICU visits per person per month is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Resource Utilization (HCRU): Number of Intensive Care Unit (ICU) Visits (Per Person Per Month)	0.00 visits per person per month Standard Deviation 0.01	0.00 visits per person per month Standard Deviation 0.02

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of total medical costs per person per month is reported. Total medical costs were estimated as the sum of medical costs (inpatient + outpatient) and pharmacy dispensation costs (drug cost + pharmacy service cost). Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Costs: Total Medical Costs (Per Person Per Month)	441.08 dollars per person per month Standard Deviation 527.43	510.42 dollars per person per month Standard Deviation 619.59

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of hospitalization costs per person per month is reported. Hospitalization costs were estimated as the total costs of services from all inpatient claims (e.g. cost for procedure, diagnostic test, medication, patient meal, and bed stay, etc.). Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Costs: Hospitalization Costs (Per Person Per Month)	176.26 dollars per person per month Standard Deviation 467.48	208.40 dollars per person per month Standard Deviation 558.44

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of outpatient medical costs per person per month is reported. Outpatient medical costs were estimated as the total costs of services from all outpatient claims (e.g. cost for procedure, diagnostic test, prescription, physician fee, etc.). Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Costs: Outpatient Medical Costs (Per Person Per Month)	92.44 dollars per person per month Standard Deviation 132.65	100.20 dollars per person per month Standard Deviation 147.37

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of outpatient pharmacy dispensation costs per person per month is reported. Outpatient pharmacy dispensation costs were estimated as the total costs of services from all outpatient pharmacy claims (pharmacy dispensing service costs + medication costs). Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
All-cause Healthcare Costs: Outpatient Pharmacy Dispensation Costs (Per Person Per Month)	172.38 dollars per person per month Standard Deviation 126.23	201.81 dollars per person per month Standard Deviation 156.85

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of COPD-related total medical costs per person per month is reported. COPD-related total medical costs were estimated as the sum of medical costs (inpatient + outpatient) of medical claims with ICD-10 codes for COPD and/or COPD-related diseases and pharmacy dispensation costs (drug costs + pharmacy service costs) of pharmacy claims including dispensation of ICS/LABA, LABA, LAMA, LABA/LAMA, short-acting beta-2 agonist (SABAs), short-acting muscarinic antagonist (SAMAs), SABA/SAMA, theophlliyne, or Phosphodiesterase-4 (PDE4) inhibitor. Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Costs: Total Medical Costs (Per Person Per Month)	243.82 dollars per person per month Standard Deviation 408.63	295.83 dollars per person per month Standard Deviation 528.06

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of COPD-related hospitalization costs per person per month is reported. COPD-related hospitalization costs were estimated as the total costs of services (e.g. costs for procedure, diagnostic test, medication, patient meal, and bed stay, etc.) from all inpatient claims (medical claims with ICD-10 codes for COPD and/or for diseases due to COPD worsening as any diagnosis).

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Costs: Hospitalization Costs (Per Person Per Month)	112.87 dollars per person per month Standard Deviation 380.37	132.22 dollars per person per month Standard Deviation 491.24

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of COPD-related outpatient medical costs per person per month is reported. COPD-related outpatient medical costs were estimated as the total costs of services (e.g. costs for procedure, diagnostic test, prescription, physician fee, etc.) from all outpatient claims (medical claims with ICD-10 codes for COPD as primary ~ 4th secondary diagnosis).

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Costs: Outpatient Medical Costs (Per Person Per Month)	21.19 dollars per person per month Standard Deviation 27.34	22.23 dollars per person per month Standard Deviation 36.53

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and Standard Deviation of COPD-related outpatient pharmacy dispensation costs per person per month is reported.

COPD related outpatient pharmacy dispensation costs were estimated as the total costs of services (pharmacy dispensing service costs + medication costs) from all outpatient pharmacy claims (pharmacy claims including dispensation of ICS/LABA, LABA, LAMA, LABA/LAMA, short-acting beta-2 agonist (SABAs), short-acting muscarinic antagonist (SAMAs), SABA/SAMA, theophlliyne, or Phosphodiesterase-4 (PDE4) inhibitor).

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Chronic Obstructive Pulmonary Disease (COPD)-Related Healthcare Costs: Outpatient Pharmacy Dispensation Costs (Per Person Per Month)	109.75 dollars per person per month Standard Deviation 101.63	141.39 dollars per person per month Standard Deviation 137.40

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of adjusted all-cause total medical costs per person per month is reported. All-cause total medical costs were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period. Total medical cost were estimated as the sum of medical costs (inpatient + outpatient) and pharmacy dispensation costs (drug costs + pharmacy service costs).

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted All-cause Costs: Total Medical Costs (Per Person Per Month)	403.08 dollars per person per month Interval 353.66 to 459.4	474.50 dollars per person per month Interval 415.29 to 542.16

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of adjusted all-cause hospitalization costs per person per month.

All-cause hospitalization costs were estimated as the total costs of services from all inpatient claims (e.g. costs for procedure, diagnostic test, medication, patient meal, and bed stay, etc.) and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted All-cause Costs: Hospitalization Costs (Per Person Per Month)	236.65 dollars per person per month Interval 177.23 to 316.0	282.58 dollars per person per month Interval 209.2 to 381.7

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of adjusted all-cause outpatient medical costs per person per month. All-cause outpatient medical costs were estimated as the total costs of services from all outpatient claims (e.g. costs for procedure, diagnostic test, prescription, physician fee, etc.) and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted All-cause Costs: Outpatient Medical Costs (Per Person Per Month)	77.41 dollars per person per month Interval 64.68 to 92.64	85.45 dollars per person per month Interval 71.88 to 101.58

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of adjusted all-cause outpatient pharmacy dispensation costs per person per month is reported. All-cause outpatient pharmacy dispensation cost were estimated as the total costs of services from all outpatient pharmacy claims (pharmacy dispensing service costs + medication costs) and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted All-cause Costs: Outpatient Pharmacy Dispensation Costs (Per Person Per Month)	161.18 dollars per person per month Interval 148.87 to 174.52	189.32 dollars per person per month Interval 175.23 to 204.54

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of adjusted COPD-related total medical costs per person per month is reported. COPD-related total medical costs were estimated as the sum of medical costs (inpatient + outpatient) of medical claims with ICD-10 codes for COPD and/or COPD-related diseases and pharmacy dispensation costs (drug costs + pharmacy service costs) of pharmacy claims including dispensation of ICS/LABA, LABA, LAMA, LABA/LAMA, short-acting beta-2 agonist (SABAs), short-acting muscarinic antagonist (SAMAs), SABA/SAMA, theophlliyne, or Phosphodiesterase-4 (PDE4) inhibitor and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted Chronic Obstructive Pulmonary Disease (COPD)-Related Costs: Total Medical Costs (Per Person Per Month)	216.37 dollars per person per month Interval 189.65 to 246.85	267.32 dollars per person per month Interval 235.25 to 303.78

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of COPD-related hospitalization costs per person per month is reported.

COPD-related hospitalization costs were estimated as the total costs of services (e.g. costs for procedure, diagnostic test, medication, patient meal, and bed stay, etc.) from all inpatient claims (medical claims with ICD-10 codes for COPD and/or for diseases due to COPD worsening as any diagnosis and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted Chronic Obstructive Pulmonary Disease (COPD)-Related Costs: Hospitalization Costs (Per Person Per Month)	178.25 dollars per person per month Interval 133.93 to 237.23	216.31 dollars per person per month Interval 162.45 to 288.01

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of COPD-related outpatient medical costs (per person per month) is reported. COPD-related outpatient medical costs were estimated as the total costs of services (e.g. costs for procedure, diagnostic test, prescription, physician fee, etc.) from all outpatient claims (medical claims with ICD-10 codes for COPD as primary ~ 4th secondary diagnosis) and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period.

Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted Chronic Obstructive Pulmonary Disease (COPD)-Related Costs: Outpatient Medical Costs (Per Person Per Month)	20.20 dollars per person per month Interval 16.66 to 24.49	20.72 dollars per person per month Interval 16.91 to 25.38

SECONDARY outcome

Timeframe: Up to 36 months from the index date. Index date was between 01 January 2005 and 30 April 2015.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Mean and 95% Confidence Interval of COPD-related outpatient pharmacy dispensation costs (per person per month) is reported. COPD related outpatient pharmacy dispensation costs were estimated as the total costs of services (pharmacy dispensing service costs + medication costs) from all outpatient pharmacy claims (pharmacy claims including dispensation of ICS/LABA, LABA, LAMA, LABA/LAMA, short-acting beta-2 agonist (SABAs), short-acting muscarinic antagonist (SAMAs), SABA/SAMA, theophlliyne, or Phosphodiesterase-4 (PDE4) inhibitor) and were adjusted for baseline characteristics and healthcare resource utilization (HCRU) and healthcare costs occurred during baseline period Costs were converted to US dollars using the average 2019 exchange rate: US$ = 1166.51 KRW (South Korean won) and were also adjusted to calendar year 2019 using the Consumer Price Index of South Korea.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Adjusted Chronic Obstructive Pulmonary Disease (COPD)-Related Costs: Outpatient Pharmacy Dispensation Costs (Per Person Per Month)	112.35 dollars per person per month Interval 102.68 to 122.92	146.53 dollars per person per month Interval 134.35 to 159.82

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Date of death event was defined as the date of death recorded in the National Health Information Database (NHID).

Incidence rate of all-cause death was calculated as below: Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of All-cause Death	9.38 patients/1000 person-years	10.09 patients/1000 person-years

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Number of patients with the event all-cause death is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With the Event All-cause Death	51 Participants	46 Participants

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Median and Inter-Quartile Range of time to death from the index date is reported. Date of death event was defined as the date of death recorded in the National Health Information Database (NHID). Time to death was estimated from the Kaplan-Meier curve.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to Death From the Index Date	609 days Interval 308.0 to 1070.0	350 days Interval 303.0 to 965.0

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. study end date), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Tuberculosis (TB) was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for pulmonary TB recorded as any diagnosis, AND 2) with special benefit costs for TB patients during the following period after the index date. To assess the incidence of TB event, the first TB event observed during the follow-up period was considered. Incidence rate of TB was calculated as below:

Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Tuberculosis (TB) Event	10.46 patients/1000 person-years	10.46 patients/1000 person-years

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Tuberculosis (TB) was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for pulmonary TB recorded as any diagnosis, AND 2) with special benefit costs for TB patients during the following period after the index date. Number of patients with tuberculosis (TB) is reported.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With Tuberculosis (TB)	56 Participants	47 Participants

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Median and Inter-Quartile Range of time to first tuberculosis (TB) event is reported. Tuberculosis (TB) was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for pulmonary TB recorded as any diagnosis, AND 2) with special benefit costs for TB patients during the following period after the index date. Date of TB was defined as the admission date of inpatient claim or the starting date of outpatient claim with the above 2 conditions to define TB event. Median and Inter-Quartile Range of time to first tuberculosis (TB) event was estimated using the Kaplan-Meier curve.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to First Tuberculosis (TB) Event From the Index Date	1 days Interval 1.0 to 116.5	86 days Interval 1.0 to 318.0

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Lung cancer was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for lung cancer recorded as any diagnosis, AND 2) with costs for patients with cancers during the following period after the index date. To assess the incidence of lung cancer event, the first lung cancer event observed during the follow-up period was considered.

Incidence rate of lung cancer was calculated as below:

Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Lung Cancer	10.64 patients/1000 person-years	11.74 patients/1000 person-years

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Number of patients with lung cancer is reported. Lung cancer was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for lung cancer recorded as any diagnosis, AND 2) with costs for patients with cancers during the following period after the index date.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With Lung Cancer	57 Participants	53 Participants

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Median and Inter-Quartile Range of time to occurrence of lung cancer from the index date.

Lung cancer was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for lung cancer recorded as any diagnosis, AND 2) with costs for patients with cancers during the following period after the index date.

Date of lung cancer diagnosis was defined as the admission date of inpatient claim or the starting date of outpatient claim with the above 2 conditions to define lung cancer event.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to Occurrence of Lung Cancer From the Index Date	91 days Interval 1.0 to 399.0	231 days Interval 77.0 to 600.0

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Non-tuberculosis mycobacteria (NTM) lung disease was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for NTM recorded as any diagnosis during the following period after the index date. To assess the incidence of NTM event, the first NTM event observed during the follow-up period was considered.

Incidence rate of NTM lung disease was calculated as below:

Incidence rate per 1000 person-years= Number of patients with event/ sum of event-free period during the follow-up period (1000 person-years)

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Incidence Rate of Non-tuberculosis Mycobacteria (NTM) Lung Disease	5.00 patients/1000 person-years	3.09 patients/1000 person-years

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Number of patients with non-tuberculosis mycobacteria (NTM) lung disease is reported. NTM lung disease was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for NTM recorded as any diagnosis during the following period after the index date.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Number of Patients With Non-tuberculosis Mycobacteria (NTM) Lung Disease	27 Participants	14 Participants

SECONDARY outcome

Timeframe: From the index date (i.e. between 01 January 2005 and 30 April 2015) up to the earliest of discontinuation of the index drug (i.e. LAMA or ICS/LABA), death, or 30 April 2016 (i.e. cut-off date for data retrieving), up to 136 months.

Population: Propensity score matching population: To address the imbalance of potential confounders between LAMA and ICS/LABA groups, treatment groups were matched using propensity scores estimated as by multiple logistic regression analysis based on age, sex, socioeconomics status, Charlson Comorbidity Index, asthma and history of chronic obstructive pulmonary disease (COPD) exacerbation.

Median and Inter-Quartile Range of Time to non-tuberculosis mycobacteria (NTM) lung disease from the index date were estimated using the Kaplan-Meier curve.

NTM lung disease was defined as ≥1 inpatient claims or outpatient claims 1) with ICD-10 codes for NTM recorded as any diagnosis during the following period after the index date.

Date of NTM was defined as the admission date of inpatient claim or the starting date of outpatient claim with the above 1 condition to define NTM event.

Outcome measures

Measure	LAMA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed long-acting muscarinic antagonists (LAMA) monotherapy between 01 January 2005 and 30 April 2015.	ICS/LABA n=2444 Participants Chronic obstructive pulmonary disease (COPD) patients who were prescribed a fixed-dose combination (FDC) of inhaled corticosteroid (ICS)/long-acting beta agonists (LABA) between 01 January 2005 and 30 April 2015.
Time to Non-tuberculosis Mycobacteria (NTM) Lung Disease From the Index Date	129 days Interval 49.0 to 815.0	360.5 days Interval 99.0 to 612.0

Adverse Events

LAMA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 51 deaths

ICS/LABA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 46 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER