Association Between Adherence to Maintenance Medication in Patients with COPD and Acute Exacerbation Occurrence and Cost in China: A Retrospective Cohort Database Study

Figures & data

Figure 1 Patient flowchart.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS/LABA, inhaled corticosteroid/long-acting beta-2 agonist.

Table 1 Baseline Characteristics of Patients in the Combination ICS/LABA Group

Characteristic	High Adherence	Poor Adherence	P-value
	(n=903)	(n=2516)
Age (years), n (%)			0.003
<65	243 (26.9)	809 (32.2)
65–74	346 (38.3)	825 (32.8)
≥75	314 (34.8)	881 (35.0)
Missing	0	1 (0.0)
Sex, n (%)			<0.001
Female	139 (15.4)	540 (21.5)
Male	764 (84.6)	1976 (78.5)
CCI (No Age Adjustment)
Mean±SD	0.03±0.18	0.02±0.18	0.1307
Median	0	0
Pre-Index AECOPD Frequency, n (%)			<0.001
0	336 (37.2)	1,306 (51.9)
1 outpatient/ED	141 (15.6)	285 (11.3)
≥2 outpatient/ED or having at least 1 hospitalized AECOPD	426 (47.2)	925 (36.8)
Pre-Index SABA Prescriptions, n (%)			0.01
0	624 (69.1)	1831 (72.8)
1–3	209 (23.2)	553 (22.0)
>3	70 (7.8)	132 (5.3)
Pre-Index LAMA Prescriptions, n (%)			<0.001
0	663 (73.4)	2049 (81.4)
1–3	84 (9.3)	254 (10.1)
>3	156 (17.3)	213 (8.5)
Pre-Index Methylxanthines Prescriptions, n (%)			<0.001
0	415 (46.0)	1540 (61.2)
1–3	196 (21.7)	565 (22.5)
>3	292 (32.3)	411 (16.3)
Pre-Index COPD-Related Cost (USD)
Mean±SD	1343±2832	992±2416	<0.001
Median	574	224
Pre-Index COPD Inpatient Visits, n (%)			0.906
0	714 (79.1)	2,006 (79.7)
1	113 (12.5)	302 (12.0)
≥2	76 (8.4)	208 (8.3)

Note: All included patients used exclusively one category of drug on the index date.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS/LABA, inhaled corticosteroid/long-acting beta-2 agonist; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; SD, standard deviation; SABA, short-acting beta-agonist; LAMA, long-acting muscarinic antagonist; CCI, Charlson Co-morbidity Index; ED, emergency department; USD, United States dollar.

Table 2 Relative Risk of Hospitalized AECOPD (High Adherence Vs Poor Adherence) in COPD Patients During the Follow-Up Period

	Odds Ratio	Standard Error	95% CI	P-value
Combination ICS/LABA user^a	0.65	0.06	0.54, 0.79	<0.001
Inhaled bronchodilator user^a	0.81	0.18	0.52, 1.26	0.339
Oral mucolytic user^b	2.51	0.55	1.63, 3.87	<0.001
Test for interaction^c,d	—	—	—	0.001

Notes: ^aLogistic regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index theophylline script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for inhaled bronchodilator and ICS/LABA user. ^bLogistic regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index LABA script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for oral mucolytic user. ^cLogistic regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for the model with interaction. ^dTest for interaction between drug category and adherence status (high or poor).

Abbreviations: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; CI, confidence interval; ICS/LABA, inhaled corticosteroid/long-acting beta-2 agonist; SABA, short-acting beta-agonist; LAMA, long-acting muscarinic antagonist.

Table 3 Incident Rate Ratio of Hospitalized AECOPD Visits (High Adherence Vs Poor Adherence) Among COPD Patients During the Follow-Up Period

	Incident Rate Ratio				High Adherence		Poor Adherence
	Mean	SE	95% CI	P-value	Predicted Mean	SE	Predicted Mean	SE
Combination ICS/LABA user^a	0.76	0.06	0.65, 0.87	<0.001	0.55	0.04	0.73	0.03
Inhaled bronchodilator user^a	0.83	0.14	0.59, 1.17	0.28	0.49	0.06	0.59	0.06
Oral mucolytic user^b	1.82	0.21	1.45, 2.29	<0.001	1.69	0.19	0.92	0.02
Test for interaction^c,d	—	—	—	<0.001	—	—	—	—

Notes: ^aNegative binomial regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index theophylline script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for inhaled bronchodilator and ICS/LABA user. ^bNegative binomial regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index LABA script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for oral mucolytic user. ^cNegative binomial regression model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, and pre-index COPD inpatient visit times for the model with interaction. ^dTest for interaction between drug category and adherence status (high or poor).

Abbreviations: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; SE, standard error; CI, confidence interval; ICS/LABA, inhaled corticosteroid/long-acting beta-2 agonist; SABA, short-acting beta-agonist; LAMA, long-acting muscarinic antagonist.

Table 4 Hospitalized AECOPD Cost Comparison (USD) Between High Adherence Cohort and Poor Adherence Cohort Among COPD Patients During the Follow-Up Period

	High Adherence		Poor Adherence		Mean Difference
	Predicted Mean	SE	Predicted Mean	SE	Mean	SE	95% CI	P-value
Combination ICS/LABA user^a	1393	186	2242	235	−848	299	−1435, −262	<0.001
Inhaled bronchodilator user^a	1556	416	1871	480	−315	636	−1560, 931	0.46
Oral mucolytic user^b	5273	1201	2053	85	3221	1204	860, 5581	<0.001
Test for interaction^c,d	—	—	—	—	—	—	—	<0.001

Notes: ^aGeneralized linear model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index theophylline script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, pre-index COPD inpatient visit times for inhaled bronchodilator and ICS/LABA user. ^bGeneralized linear model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index LABA script number, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, pre-index COPD inpatient visit times for oral mucolytic user. ^cGeneralized linear model with the high adherence as the primary exposure and adjusted for age, gender, pre-index AECOPD frequency, Charlson comorbidity index, pre-index SABA script number, pre-index LAMA script number, pre-index COPD related cost, pre-index COPD inpatient visit times for the model with interaction. ^dTest for interaction between drug category and adherence status (high or poor).

Abbreviations: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; SE, standard error; CI, confidence interval; USD, United States dollar; ICS/LABA, inhaled corticosteroid/long-acting beta-2 agonist; SABA, short-acting beta-agonist; LAMA, long-acting muscarinic antagonist.