Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The objective of this study was to examine COPD-related outcomes for patients with comorbid depression/anxiety who are on combination fluticasone propionate/salmeterol xinafoate compared to those receiving anticholinergics. The prevalence of comorbid depression/anxiety in patients with chronic obstructive pulmonary disease (COPD) is estimated to be high and range from 10-40%, given that the risk of depression/anxiety symptoms is almost 3 times higher in patients with versus without COPD. Additionally, patients with comorbid COPD and depression/anxiety have higher COPD-related healthcare utilization and costs compared to those without depression/anxiety. Therapy with maintenance medications for COPD has been recommended to prevent future adverse COPD outcomes, but the impact of initiating these interventions has not yet been evaluated in a higher-risk population with comorbid COPD-depression/anxiety. The present study compares the risk of COPD exacerbations and COPD-related costs in patients initiating maintenance medications for treatment of COPD in a comorbid COPD/depression-anxiety population. Maintenance medications include inhaled corticosteroid (ICS), long-acting beta agonist (LABA), combination drug product of ICS+LABA, and anti-cholinergics (AC) including tiotropium (TIO) and ipratropium or combination ipratropium-albuterol (collectively abbreviated as IPR).
Detailed description
This was a retrospective cohort study using a large administrative database (study period: 1/1/2003 through 6/30/2009). Date of first FSC or ACs (tiotropium; ipratropium alone or in combination with albuterol) was defined as the index date. Managed care enrollees (aged \>40 years) having at least one medical claim with a primary diagnosis of COPD (ICD code 491.xx, 492.xx and 496.xx) and a diagnosis of depression (at least one claim with depression/anxiety or at least one prescription claim for depression/anxiety) in one-year pre-index and within 60-days post-index were defined in the comorbid population. Patients were continuously eligible throughout the one-year pre and post-index periods. Negative binomial models were used to analyze number of COPD-related events \[hospitalization (IP), emergency department (ED), office visits with oral steroid and/or antibiotic prescription within 5 days (OV+Rx)\] and logistic regression was used to examine risk of COPD events between the two cohorts. COPD-related costs were compared between the two cohorts using - generalized linear model with log-link/gamma distribution after adjusting for baseline differences. Specifically the study hypothesis for the primary outcome being tested was: Ho: There is no difference in risk of any COPD-related exacerbation between FSC and AC cohorts Ha: There is a difference in risk of any COPD-related exacerbation between FSC and AC cohorts Hypothesis for the key secondary outcome of COPD-related costs that was tested was: Ho: There is no difference in COPD-related costs between FSC and AC cohorts Ha: There is a difference in COPD-related costs between FSC and AC cohorts
Interventions
combination fluticasone priopionate and salmeterol xinafoate 250/50mcg
DRUGAnticholinergics
tiotropium; ipratropium alone; or ipratropium + albuterol
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
* Diagnosis of COPD in any field in the pre-index period and 60 days after the index date * Diagnosis of depression/anxiety in any field and a medication for treating depression/anxiety in the pre-index period and 60 days after the index date * Index date occurs during identification period * Patients must be continuously eligible during 1-year pre and 1-year post-index date and be of at least 40 years of age
Exclusion criteria
* comorbid conditions (respiratory cancer, cystic fibrosis, fibrosis due to tuberculosis, and bronchiectasis, pneumonociosis, pulmonary fibrosis, pulmonary tuberculosis, sarcoidosis) during the 1 year pre or post-index periods * No other maintenance medications other than the index medication on or 60 days after the index date
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Chronic Obstructive Pulmonary Disease (COPD)-Related Exacerbation | Maximum of 1 year after index date (January 1, 2004 to June 30, 2009) | The number of participants with any of the following COPD-related exacerbations during the follow-up period was computed: COPD-related hospitalization, emergency room (ER) visit, or physician visit with a prescription (Rx) for oral corticosteroid (OCS) or antibiotic within 5 days of the visit. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Indicated COPD-related Exacerbations | Maximum of 1 year after index date (January 1, 2004 through June 30, 2009) | The number of participants with a COPD-related exacerbation was identified during the follow-up period. Four types of COPD-related exacerbations were defined: COPD-related hospitalization, ER visit, physician visit with a prescription (Rx) for oral corticosteroid or antibiotic within 5 days of the visit, or combined occurrence of COPD-related hospitalization/ER visit. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008. |
| Mean Annual COPD-related Costs Per Participant | Maximum of 1 year after index date (January 1, 2004 through June 30, 2009) | Cost categories included medical, pharmacy, and total (calculated as the sum of medical and pharmacy). COPD-related medical costs were computed using claims with a primary diagnosis of COPD, and COPD-related pharmacy costs were computed using the paid amounts of pharmacy claims for prescription medication used for COPD.The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008. |
| Number of the Indicated COPD-related Exacerbations | Maximum of 1 year after index date (January 1, 2004 through June 30, 2009) | The number of COPD-related exacerbations was identified during the follow-up period. Five types of COPD-related exacerbations were defined: -COPD-related hospitalization, ER visit, physician visit with a prescription (Rx) for oral corticosteroid or antibiotic within 5 days of the visit, combined occurrence of COPD-related hospitalization/ER visit, or combined occurrence of any COPD-related exacerbation. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FSC Cohort Fluticasone/Salmeterol Combination (FSC) 250/50 micrograms (mcg) twice a day | 1,078 |
| AC Cohort Anticholinergics (AC) include Tiotropium, Ipratropium, and Ipratropium-albuterol combination drug product. Due to the retrospective nature of this study, dosing information is not available. | 2,923 |
| Total | 4,001 |
Baseline characteristics
| Characteristic | FSC Cohort | AC Cohort | Total |
|---|---|---|---|
| Age, Continuous | 57.8 Years STANDARD_DEVIATION 9.8 | 60.3 Years STANDARD_DEVIATION 10.3 | 59.6 Years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 742 Participants | 1910 Participants | 2652 Participants |
| Sex: Female, Male Male | 336 Participants | 1013 Participants | 1349 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
Number of Participants With Any Chronic Obstructive Pulmonary Disease (COPD)-Related Exacerbation
The number of participants with any of the following COPD-related exacerbations during the follow-up period was computed: COPD-related hospitalization, emergency room (ER) visit, or physician visit with a prescription (Rx) for oral corticosteroid (OCS) or antibiotic within 5 days of the visit. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008.
Time frame: Maximum of 1 year after index date (January 1, 2004 to June 30, 2009)
Population: Managed care enrollees (aged \>=40 years) diagnosed with COPD (ICD code 491.xx, 492.xx, and 496.xx) and depression/anxiety before or within 60 days of the date of first prescription for a maintenance medication for COPD (index date).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FSC Cohort | Number of Participants With Any Chronic Obstructive Pulmonary Disease (COPD)-Related Exacerbation | 200 participants |
| AC Cohort | Number of Participants With Any Chronic Obstructive Pulmonary Disease (COPD)-Related Exacerbation | 674 participants |
p-value: 0.00295% CI: [1.08, 1.56]Chi-squared
Secondary
Mean Annual COPD-related Costs Per Participant
Cost categories included medical, pharmacy, and total (calculated as the sum of medical and pharmacy). COPD-related medical costs were computed using claims with a primary diagnosis of COPD, and COPD-related pharmacy costs were computed using the paid amounts of pharmacy claims for prescription medication used for COPD.The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008.
Time frame: Maximum of 1 year after index date (January 1, 2004 through June 30, 2009)
Population: Managed care enrollees (aged \>=40 years) diagnosed with COPD (ICD code 491.xx, 492.xx, and 496.xx) and depression/anxiety before or within 60 days of the date of first prescription for a maintenance medication for COPD (index date).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FSC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related total costs | 1604 United States (US) dollars | Standard Deviation 3187 |
| FSC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related pharmacy costs | 934 United States (US) dollars | Standard Deviation 814 |
| FSC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related medical costs | 670 United States (US) dollars | Standard Deviation 2923 |
| AC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related total costs | 1687 United States (US) dollars | Standard Deviation 4299 |
| AC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related pharmacy costs | 684 United States (US) dollars | Standard Deviation 724 |
| AC Cohort | Mean Annual COPD-related Costs Per Participant | COPD-related medical costs | 1003 United States (US) dollars | Standard Deviation 4095 |
Secondary
Number of Participants With the Indicated COPD-related Exacerbations
The number of participants with a COPD-related exacerbation was identified during the follow-up period. Four types of COPD-related exacerbations were defined: COPD-related hospitalization, ER visit, physician visit with a prescription (Rx) for oral corticosteroid or antibiotic within 5 days of the visit, or combined occurrence of COPD-related hospitalization/ER visit. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008.
Time frame: Maximum of 1 year after index date (January 1, 2004 through June 30, 2009)
Population: Managed care enrollees (aged \>=40 years) diagnosed with COPD (ICD code 491.xx, 492.xx, and 496.xx) and depression/anxiety before or within 60 days of the date of first prescription for a maintanance medication for COPD (index date).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FSC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related hospitalization | 35 participants |
| FSC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related physician + Rx visit | 156 participants |
| FSC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related ER visit | 37 participants |
| FSC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit | 63 participants |
| AC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit | 307 participants |
| AC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related hospitalization | 168 participants |
| AC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related ER visit | 171 participants |
| AC Cohort | Number of Participants With the Indicated COPD-related Exacerbations | COPD-related physician + Rx visit | 448 participants |
p-value: 0.00295% CI: [1.02, 2.38]Chi-squared
p-value: 0.00295% CI: [1.14, 2.39]Chi-squared
p-value: 0.50395% CI: [0.93, 1.4]Chi-squared
p-value: <0.00195% CI: [1.26, 2.31]Chi-squared
Secondary
Number of the Indicated COPD-related Exacerbations
The number of COPD-related exacerbations was identified during the follow-up period. Five types of COPD-related exacerbations were defined: -COPD-related hospitalization, ER visit, physician visit with a prescription (Rx) for oral corticosteroid or antibiotic within 5 days of the visit, combined occurrence of COPD-related hospitalization/ER visit, or combined occurrence of any COPD-related exacerbation. The index date is defined as the date of first chronologically occurring COPD maintenance medication of interest during an identification period spanning January 1, 2004 to June 30, 2008.
Time frame: Maximum of 1 year after index date (January 1, 2004 through June 30, 2009)
Population: Managed care enrollees (aged \>=40 years) diagnosed with COPD (ICD code 491.xx, 492.xx, and 496.xx) and depression/anxiety before or within 60 days of the date of first prescription for a maintenance medication for COPD (index date).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FSC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related ER visit | 0.06 number of exacerbations | Standard Deviation 0.4 |
| FSC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit | 0.09 number of exacerbations | Standard Deviation 0.5 |
| FSC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related physician (phy)+Rx visit | 0.19 number of exacerbations | Standard Deviation 0.6 |
| FSC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit/phy+Rx visit | 0.29 number of exacerbations | Standard Deviation 0.8 |
| FSC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization | 0.04 number of exacerbations | Standard Deviation 0.2 |
| AC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit/phy+Rx visit | 0.34 number of exacerbations | Standard Deviation 0.8 |
| AC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization | 0.07 number of exacerbations | Standard Deviation 0.3 |
| AC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related ER visit | 0.07 number of exacerbations | Standard Deviation 0.4 |
| AC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related physician (phy)+Rx visit | 0.20 number of exacerbations | Standard Deviation 0.6 |
| AC Cohort | Number of the Indicated COPD-related Exacerbations | COPD-related hospitalization/ER visit | 0.14 number of exacerbations | Standard Deviation 0.5 |
p-value: 0.000495% CI: [1.01, 2.09]t-test, 2 sided
p-value: 0.20895% CI: [0.89, 1.82]t-test, 2 sided
p-value: 0.67195% CI: [0.9, 1.32]t-test, 2 sided
p-value: 0.00995% CI: [1.05, 1.72]t-test, 2 sided
p-value: 0.05295% CI: [0.98, 1.37]t-test, 2 sided