Exacerbations, health services utilization, and costs in commercially-insured COPD patients treated with nebulized long-acting β2-agonists

Figures & data

Figure 1. Study design. LABA, long-acting β2-agonist; PDC, proportion of days covered by index prescription fills within 1 year post-index.

Figure 2. Selection flow chart by eligibility criteria. COPD, chronic obstructive pulmonary disease; LABA, long-acting β2-agonist; PDC, proportion of days covered by index prescription fills within 1 year post-index.

Table 1. Demographic and clinical characteristics of patients.

Variable	Adherent or partially adherent patients (n = 417)
Demographic characteristics profile at index	Nebulized arformoterol (n = 274)		Nebulized formoterol (n = 143)		p value
	n	%	n	%
Age group (years)					0.729
35–54	11	4.0	8	5.6
55–64	68	24.8	33	23.1
≥65	195	71.2	102	71.3
Gender					0.650
Female	122	44.5	67	46.9
Male	152	55.5	76	53.1
Geographic region					0.678
Northeast	30	10.9	18	12.6
Midwest	102	37.2	52	36.4
South	118	43.1	56	39.2
West	24	8.8	17	11.9
Health plan type					0.004
HMO	21	7.7	15	10.5
Indemnity	41	15.0	14	9.8
PPO	210	76.6	105	73.4
Other/unknown	2	0.7	9	6.3
Payer type					0.150
Commercial	112	40.9	70	49.0
Self-insured/group insurance	145	52.9	61	42.7
Medicare risk	15	5.5	9	6.3
Other/unknown	2	0.7	3	2.1
Prescribing physician specialty					0.446
General/family practice	21	8.0	10	7.0
Internal medicine	19	7.0	7	5.0
Pulmonary medicine	94	34.0	54	38.0
Other/unknown	140	51.0	72	50.3
Clinical characteristics at 180 days pre-index
Use of other COPD-related therapies
Antibiotics (oral)	169	61.6	104	72.7	0.024
Anticholinergic bronchodilators	135	49.2	75	52.4	0.538
Non-nebulized LABAs	128	46.7	68	47.5	0.871
Non-nebulized SABAs	43	15.6	22	15.3	0.934
Corticosteroids (oral)	132	48.1	78	54.5	0.217
Leukotriene modulators	34	12.4	16	11.1	0.716
Nebulized SABAs	91	33.2	67	46.8	0.006
Steroid inhalants	73	26.6	34	23.7	0.525
Spirometry testing	101	36.8	52	36.3	0.920
COPD exacerbations	156	56.9	98	68.5	0.021
Distribution of exacerbation event frequency
0	118	43.1	45	31.4	0.067
1	53	19.3	27	18.8
2	35	12.7	29	20.2
3	21	7.6	12	8.3
4	12	4.4	7	4.8
5+	35	12.7	23	16.1
Mean (±SD)	1.9 (3.3)		2.4 (3.4)		0.692
Comorbidities
Hypertension	149	54.3	71	49.6	0.359
Hyperlipidemia	83	30.2	44	30.7	0.920
Congestive heart failure	49	17.8	21	14.6	0.407
Diabetes	57	20.8	26	18.1	0.525
Deficiency anemia	30	10.9	11	7.6	0.289
Depression	28	10.2	8	5.5	0.111
Dyspnea and respiratory abnormalities	119	43.4	66	46.1	0.595
Cough	35	12.7	25	17.4	0.193
Charlson Comorbidity Index, mean (±SD)	2.6 (1.8)		2.3 (1.8)		0.040
COPD-related total costs, median	$2497		$2957		0.054

COPD, chronic obstructive pulmonary disease; HMO, health maintenance organization; LABA, long-acting β2-agonist; PPO, preferred provider organization; SABA, short-acting β2-agonist; SD, standard deviation.

Table 2. Cox proportional hazard model of the risk of exacerbation 1 year post-index among adherent or partially adherent patients (n = 417).

Independent variable	Hazard ratio	95% CI
		Lower	Upper
Index therapy: nebulized arformoterol	0.81*	0.64	1.03
Age: 35–64 years old	1.06	0.82	1.38
Male	0.99	0.77	1.26
Prescriber physician specialty: pulmonology	1.07	0.83	1.38
Payer type: non-commercially insured	1.57*	0.97	2.55
Health plan type: non-PPO	0.70†	0.51	0.96
Pre-index use of oral corticosteroids	2.07†	1.59	2.69
Pre-index history of hyperlipidemia	0.78*	0.58	1.05
Pre-index history of depression	2.20†	1.48	3.27
Pre-index COPD-related ED visits	0.83	0.60	1.15
Pre-index COPD-related hospitalizations	0.82	0.61	1.11

*p < 0.10; †p < 0.05; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ED, emergency department; PPO, preferred provider organization.

Table 3. COPD-related health services utilization at 1-year post-index.

Service use by type	Nebulized arformoterol (n = 274)	Nebulized formoterol (n = 143)	Test on means
	n (%), mean (SD)	n (%), mean (SD)	p value
Pharmacy services – number of prescriptions per COPD patient
Nebulizer LABA therapy	274 (100), 10.1 (2.9)	143 (100), 9.8 (2.8)	0.266
Anti-asthmatic monoclonal antibodies	2 (0.7), 0.1 (0.8)	0 (0), 0 (0)	0.350
Antibiotics	204 (74.5), 3.0 (3.6)	111 (77.6), 3.8 (4.3)	0.035
Anticholinergic bronchodilators	157 (57.3), 3.9 (4.6)	76 (53.1), 3.6 (4.7)	0.501
Non-nebulizer LABAs	55 (20.1), 0.7 (1.9)	28 (19.6), 0.9 (2.4)	0.287
Non-nebulizer SABAs	35 (12.8), 0.6 (2.0)	23 (16.1), 0.9 (2.8)	0.113
Corticosteroids	167 (60.9), 2.6 (3.5)	82 (57.3), 2.8 (3.9)	0.673
Leukotriene modulators	38 (13.9), 0.7 (2.2)	19 (13.3), 0.8 (2.5)	0.877
PDE-4 inhibitors	6 (2.2), 0.1 (0.5)	2 (1.4), 0 (0.4)	0.744
Nebulizer SABAs	105 (38.3), 1.8 (3.2)	53 (37.1), 2.0 (3.6)	0.578
Steroid inhalants	185 (67.5), 6.0 (5.2)	105 (73.4), 6.3 (5.1)	0.545
Xanthines	26 (9.5), 0.6 (2.1)	13 (9.1), 0.5 (1.9)	0.649
All other pharmacy services	58 (21.2), 0.9 (3.0)	32 (22.4), 0.9 (2.5)	0.860
Other outpatient services – number of encounters per COPD patient
Spirometry testing	88 (32.1), 0.5 (0.9)	40 (28.0), 0.5 (1.1)	0.751
Oxygen therapy	157 (57.3), 8.7 (9.5)	78 (54.5), 9.9 (12.2)	0.266
Non-invasive mechanical ventilation	11 (4.0), 0.4 (2.5)	6 (4.2), 0.6 (3.3)	0.605
Emergency department	64 (23.4), 0.3 (0.6)	30 (21.0), 0.3 (0.8)	0.572
Physician office	254 (92.7), 6.0 (6.0)	138 (96.5), 6.3 (5.1)	0.497
Laboratory and pathology	96 (35.0), 2.4 (7.3)	50 (35.0), 2.4 (6.7)	0.943
Radiology	118 (43.1), 0.9 (1.5)	55 (38.5), 0.7 (1.1)	0.120
Ambulatory surgical services	15 (5.5), 0.1 (0.5)	8 (5.6), 0.1 (0.4)	0.717
Ancillary services^a	263 (96.0), 21.2 (24.7)	136 (95.1), 14.4 (10.8)	0.002
Inpatient services per COPD patient
Hospital admissions	79 (28.8), 0.38 (0.82)	41 (28.7), 0.43 (0.75)	0.566
Re-admissions within 30 days after discharge	6 (7.6), 0.14 (0.71)	5 (12.2), 0.12 (0.33)	0.879
Average annual inpatient days^b	8.4 (9.3)	9.3 (7.3)	0.701
Average length in days of an inpatient stay^b	6.4 (6.1)	6.2 (5.0)	0.863

COPD, chronic obstructive pulmonary disease; LABA, long-acting β2-agonist; PDE-4, phosphodiesterase-4; SABA, short-acting β2-agonist; SD, standard deviation.

^aIncludes diagnostic imaging, genetic testing, rehabilitation services, urgent care and other similar services; ^bMean (SD) only.

Table 4. COPD-related medical care costs at 1 year post-index.

COPD-related costs by category per patient	Nebulized arformoterol			Nebulized formoterol			p value of test on
	n	Mean (±SD)	Median	n	Mean (±SD)	Median	Mean	Median
Among all patients
Total medical care costs	274	$20,001 ($42,690)	$11,715	143	$21,031 ($27,904)	$12,769	0.794	0.177
Pharmacy services	274	$7381 ($3711)	$7215	143	$7840 ($3364)	$7276	0.217	0.140
Outpatient services	274	$4594 ($8560)	$2478	143	$4072 ($6561)	$2494	0.523	0.905
Inpatient services	274	$8026 ($39,427)	$0	143	$9120 ($26,403)	$0	0.765	–
Among patients with ≥1 inpatient admission
Cost per inpatient stay	79	$21,144 ($61,239)	$9542	41	$21,379 ($28,674)	$14,025	0.978	0.009
Costs per inpatient day	79	$3290 ($3858)	$2266	41	$3792 ($3580)	$3048	0.409	0.085
Among patients with re-admission within 30 days of discharge
Cost per inpatient stay	6	$9092 ($6949)	$7392	5	$20,271 ($13,712)	$18,018	0.004	0.006
Costs per inpatient day	6	$1472 ($1003)	$1357	5	$2799 ($1509)	$3094	0.006	0.018

COPD, chronic obstructive pulmonary disease; SD, standard deviation.

Table 5. Generalized linear model (GLM) estimates of mean COPD-related total costs at 1 year post-index.

Independent variables of GLM	Exponentiated parameter estimate	p value
At index
Index therapy: nebulized arformoterol	0.856	0.062
Age 35–64 years	1.277	0.006
Male	1.295	0.002
Geographic region (reference: South)
Midwest	1.043	0.638
Northeast	1.504	0.002
West	1.233	0.136
Health plan type: non-PPO	0.590	<0.0001
Prescriber physician specialty:  pulmonology	1.298	0.002
180 days pre-index
Use of anticholinergic bronchodilators	1.216	0.028
Use of combination of steroid inhalant  therapy and non-nebulized  adrenergic therapy	1.178	0.079
Use of oral corticosteroids	1.166	0.092
Use of non-nebulized LABA therapy	1.041	0.657
Use of any SABA therapy	0.813	0.014
History of hypertension	1.138	0.134
History of hyperlipidemia	0.888	0.201
History of congestive heart failure	1.348	0.007
History of diabetes	0.918	0.396
History of deficiency anemia	1.008	0.950
History of depression	0.899	0.451
History of hypothyroidism	1.347	0.042
History of valvular disease	0.843	0.666
History of cough	0.790	0.038
Number of pre-index COPD  exacerbations	1.061	<0.0001

COPD, chronic obstructive pulmonary disease; LABA, long-acting β2-agonist; PPO, preferred provider organization; SABA, short-acting β2-agonist.