Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
chronic obstructive pulmonary disease, cost and cost analysis, bronchodilators, healthcare utilization, fluticasone propionate/salmeterol, tiotropium
Brief summary
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by inflammation-mediated damage to lung tissue. Although damage to lung tissue in COPD appears to be irreversible, evidence suggests that the course of COPD can be altered through measures such as smoking cessation, pulmonary rehabilitation, and the use of pharmacotherapy for bronchodilation. A primary goal of maintenance pharmacotherapy is to reduce the incidence of acute exacerbations and the associated hospitalizations and emergency department (ED) visits. Bronchodilation in COPD maintenance therapy can be accomplished with the long-acting anticholinergic tiotropium (TIO), long acting beta-agonists (e.g. formoterol, salmeterol), methylxanthines (e.g. theophylline), or combination therapy with a long-acting beta-agonist and an inhaled corticosteroid (e.g. fluticasone propionate/salmeterol \[FSC\]). The objective of this study is to compare the benefits of combination long-acting beta-agonist/inhaled corticosteroid therapy to long-acting anticholinergic therapy. The study compares the risk of COPD exacerbations and COPD-related healthcare utilization and costs for commercially-insured patients age 40 and older who were prescribed FSC to those prescribed TIO. The null hypothesis is that no difference exists between the costs and outcomes of COPD patients treated with TIO and those treated with FSC. The test hypothesis is that patients treated with either TIO or FSC will incur lower costs and use fewer healthcare resources for the management of COPD. The source of data for this study was the Ingenix Impact database (formerly the Integrated Healthcare Information Services \[IHCIS\] database). This is an administrative claims database that includes patient-level data on enrollment, facility, professional, and pharmacy services from approximately 50 million patients covered by more than 40 managed care health plans across the United States (US). The study design is a retrospective cohort study.
Interventions
DRUGfluticasone propionate/salmeterol 250µg/50µg (FSC)
Patient records with evidence of COPD and prescription claims for FSC
DRUGtiotropium bromide (TIO)
Patient records with evidence of COPD and prescription claims for TIO
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is age 40 or older * Patient record indicates a new prescription claim for fluticasone propionate/salmeterol (FSC) or tiotropium bromide (TIO) (first pharmacy claim defines the index date) * Patient records include at least two medical claims with a primary or non-primary diagnosis of COPD (International Classification of Disease-9 \[ICD-9\] code 490.xx - 492.xx or 496.xx) * At least one of the patient's ICD-9 codes for COPD is observed in the 12 months prior to the first pharmacy claim for FSC or TIO (the index date)
Exclusion criteria
* A pharmacy claim for FSC or TIO prior to the index date * The patient initiated FSC at a dose other than 250µg/50µg * The patient initiated FSC and TIO at the same time * The patient had one or more prescription with missing dosing information * The patient had a prescription claim for the study medication other than the one they started on at the index date within 60 days after the index date
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-index Period COPD-related, Unadjusted Costs | 1 year | The mean cost per participant for COPD-related healthcare interventions for one year following the index date (first pharmacy claim for fluticasone propionate/salmeterol 250 µg/50 µg \[FSC\] or tiotropium bromide \[TIO\]) was calculated. Total medical costs included inpatient, emergency department, and outpatient costs associated with the treatment of COPD. Total pharmacy costs included costs of all COPD-related medications, and total healthcare costs included all medical and pharmacy costs that were related to COPD treatment. These costs were unadjusted and reflect the actual costs. |
| Mean Number of COPD Exacerbations | 1 year | Moderate COPD exacerbations were defined as the occurrence of a COPD-related emergency department (ED) visit or a COPD-related office visit that is closely followed by a prescription claim for oral steroids or antibiotics. Severe exacerbations were defined as the occurrence of a COPD-related hospital admission. |
Secondary
| Measure | Time frame |
|---|---|
| Number of COPD-related Healthcare Encounters | 1 year |
Participant flow
Pre-assignment details
Participants were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymized and used to develop a cohort. All diagnoses and treatments are recorded in the course of routine medical practice.
Participants by arm
| Arm | Count |
|---|---|
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg Participants 40 years of age or older with \>=2 medical claims with a primary or non-primary diagnosis of COPD (ICD-9-CM code 490.xx, 491.xx, 492.xx, or 496.xx), \>=1 in the 12 months prior to the index date (defined as the first pharmacy claim for the study drug), \>=1 in the post-index date observation period, and \>=1 prescription claim for FSC | 11,582 |
| Tiotropium Bromide 18 µg Participants 40 years of age or older with \>=2 medical claims with a primary or non-primary diagnosis of COPD (ICD-9-CM code 490.xx, 491.xx, 492.xx, or 496.xx), \>=1 in the 12 months prior to the index date (defined as the first pharmacy claim for the study drug), \>=1 in the post-index date observation period, and \>=1 prescription claim for TIO | 10,641 |
| Total | 22,223 |
Baseline characteristics
| Characteristic | Total | Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Tiotropium Bromide 18 µg |
|---|---|---|---|
| Age, Continuous | 61.9 Years STANDARD_DEVIATION 10.4 | 60.8 Years STANDARD_DEVIATION 10.6 | 63.1 Years STANDARD_DEVIATION 10 |
| Charlson Comorbidity Score | 1.6 scores on a scale STANDARD_DEVIATION 2.1 | 1.6 scores on a scale STANDARD_DEVIATION 2.1 | 1.6 scores on a scale STANDARD_DEVIATION 2.2 |
| Number of Participants with the Indicated COPD Severity Mild | 17918 participants | 9442 participants | 8476 participants |
| Number of Participants with the Indicated COPD Severity Moderate | 1270 participants | 750 participants | 520 participants |
| Number of Participants with the Indicated COPD Severity Severe | 3035 participants | 1390 participants | 1645 participants |
| Number of participants with the indicated payer source Commercial | 19460 participants | 10233 participants | 9227 participants |
| Number of participants with the indicated payer source Medicaid | 171 participants | 121 participants | 50 participants |
| Number of participants with the indicated payer source Medicare | 2592 participants | 1228 participants | 1364 participants |
| Number of the Indicated Pre-Index Period COPD-related comorbidities Asthma | 4977 number of comorbidities | 3326 number of comorbidities | 1651 number of comorbidities |
| Number of the Indicated Pre-Index Period COPD-related comorbidities Congestive heart failure | 3096 number of comorbidities | 1472 number of comorbidities | 1624 number of comorbidities |
| Number of the Indicated Pre-Index Period COPD-related comorbidities Lower respiratory infection | 1006 number of comorbidities | 531 number of comorbidities | 475 number of comorbidities |
| Number of the Indicated Pre-Index Period COPD-related comorbidities Upper respiratory infection | 7347 number of comorbidities | 4395 number of comorbidities | 2952 number of comorbidities |
| Number of the Indicated Pre-Index Period Treatments Long-acting beta-agonist use | 798 number of treatments | 242 number of treatments | 556 number of treatments |
| Number of the Indicated Pre-Index Period Treatments Oxygen use | 2727 number of treatments | 1210 number of treatments | 1517 number of treatments |
| Region of Enrollment Midwest | 3521 Participants | 1790 Participants | 1731 Participants |
| Region of Enrollment National or Unknown | 670 Participants | 366 Participants | 304 Participants |
| Region of Enrollment Northeast | 8672 Participants | 4523 Participants | 4149 Participants |
| Region of Enrollment South | 7448 Participants | 3818 Participants | 3630 Participants |
| Region of Enrollment West | 1912 Participants | 1085 Participants | 827 Participants |
| Sex: Female, Male Female | 11079 Participants | 6121 Participants | 4958 Participants |
| Sex: Female, Male Male | 11144 Participants | 5461 Participants | 5683 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Mean Number of COPD Exacerbations
Moderate COPD exacerbations were defined as the occurrence of a COPD-related emergency department (ED) visit or a COPD-related office visit that is closely followed by a prescription claim for oral steroids or antibiotics. Severe exacerbations were defined as the occurrence of a COPD-related hospital admission.
Time frame: 1 year
Population: The total population including participants with index dates between January 1,2004 and June 30, 2008.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Mean Number of COPD Exacerbations | Moderate Exacerbation | 0.35 number of exacerbations | Standard Deviation 0.77 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Mean Number of COPD Exacerbations | Severe Exacerbation | 0.05 number of exacerbations | Standard Deviation 0.29 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Mean Number of COPD Exacerbations | Any Exacerbation | 0.4 number of exacerbations | Standard Deviation 0.87 |
| Tiotropium Bromide 18 µg | Mean Number of COPD Exacerbations | Moderate Exacerbation | 0.29 number of exacerbations | Standard Deviation 0.71 |
| Tiotropium Bromide 18 µg | Mean Number of COPD Exacerbations | Severe Exacerbation | 0.05 number of exacerbations | Standard Deviation 0.32 |
| Tiotropium Bromide 18 µg | Mean Number of COPD Exacerbations | Any Exacerbation | 0.34 number of exacerbations | Standard Deviation 0.82 |
p-value: 0.219895% CI: [0.909, 1.022]Regression, Cox
p-value: 0.040695% CI: [0.752, 0.994]Regression, Cox
p-value: 0.096295% CI: [0.901, 1.009]Regression, Cox
Primary
Post-index Period COPD-related, Unadjusted Costs
The mean cost per participant for COPD-related healthcare interventions for one year following the index date (first pharmacy claim for fluticasone propionate/salmeterol 250 µg/50 µg \[FSC\] or tiotropium bromide \[TIO\]) was calculated. Total medical costs included inpatient, emergency department, and outpatient costs associated with the treatment of COPD. Total pharmacy costs included costs of all COPD-related medications, and total healthcare costs included all medical and pharmacy costs that were related to COPD treatment. These costs were unadjusted and reflect the actual costs.
Time frame: 1 year
Population: A subpopulation of participants with an index date between January 1, 2004 and September 30, 2007
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Inpatient services | 688 United States (US) dollars | Standard Deviation 4998 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Emergency department visits | 55 United States (US) dollars | Standard Deviation 415 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Inpatient and emergency department visits | 743 United States (US) dollars | Standard Deviation 5090 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Office visits | 231 United States (US) dollars | Standard Deviation 388 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Other outpatient/ancillary services | 734 United States (US) dollars | Standard Deviation 2504 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Total medical costs | 1709 United States (US) dollars | Standard Deviation 6322 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Total pharmacy costs | 1291 United States (US) dollars | Standard Deviation 1791 |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Post-index Period COPD-related, Unadjusted Costs | Total healthcare utilization | 3000 United States (US) dollars | Standard Deviation 6805 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Office visits | 293 United States (US) dollars | Standard Deviation 559 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Inpatient services | 867 United States (US) dollars | Standard Deviation 6887 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Total medical costs | 2091 United States (US) dollars | Standard Deviation 8302 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Emergency department visits | 52 United States (US) dollars | Standard Deviation 363 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Total healthcare utilization | 3299 United States (US) dollars | Standard Deviation 8536 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Other outpatient/ancillary services | 879 United States (US) dollars | Standard Deviation 3050 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Inpatient and emergency department visits | 919 United States (US) dollars | Standard Deviation 6977 |
| Tiotropium Bromide 18 µg | Post-index Period COPD-related, Unadjusted Costs | Total pharmacy costs | 1209 United States (US) dollars | Standard Deviation 1378 |
95% CI: [5857, 9045]
95% CI: [8827, 14263]
95% CI: [58, 63]
95% CI: [49, 53]
95% CI: [227, 234]
95% CI: [290, 299]
95% CI: [827, 919]
95% CI: [1022, 1138]
95% CI: [1251, 1283]
95% CI: [1234, 1266]
95% CI: [1083, 1267]
95% CI: [1438, 1695]
95% CI: [2922, 3059]
95% CI: [3221, 3386]
Secondary
Number of COPD-related Healthcare Encounters
Time frame: 1 year
Population: A subpopulation of participants with an index date between January 1, 2004 and September 30, 2007
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Number of COPD-related Healthcare Encounters | Inpatient and emergency department visits | 3673 number of encounters |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Number of COPD-related Healthcare Encounters | Inpatient services | 2155 number of encounters |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Number of COPD-related Healthcare Encounters | Emergency department visits | 3085 number of encounters |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Number of COPD-related Healthcare Encounters | Other outpatient/ancillary services | 7243 number of encounters |
| Fluticasone Propionate/Salmeterol 250 Micrograms (µg)/50 µg | Number of COPD-related Healthcare Encounters | Office visits | 7833 number of encounters |
| Tiotropium Bromide 18 µg | Number of COPD-related Healthcare Encounters | Other outpatient/ancillary services | 5859 number of encounters |
| Tiotropium Bromide 18 µg | Number of COPD-related Healthcare Encounters | Emergency department visits | 2312 number of encounters |
| Tiotropium Bromide 18 µg | Number of COPD-related Healthcare Encounters | Inpatient and emergency department visits | 2817 number of encounters |
| Tiotropium Bromide 18 µg | Number of COPD-related Healthcare Encounters | Office visits | 6295 number of encounters |
| Tiotropium Bromide 18 µg | Number of COPD-related Healthcare Encounters | Inpatient services | 1792 number of encounters |