Umeclidinium/Vilanterol Compared with Fluticasone Propionate/Salmeterol, Budesonide/Formoterol, and Tiotropium as Initial Maintenance Therapy in Patients with COPD Who Have High Costs and Comorbidities

Figures & data

Figure 1 Study design.

Abbreviations: B/F, budesonide/formoterol; FP/SAL, fluticasone propionate/salmeterol; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.

Figure 2 Patient disposition. ^aICD codes for COPD are shown in Table S1. ^bICD codes for asthma included ICD-9-CM: 493.xx; ICD-10-CM: J45.3, J45.4, J45.5, J45.9. ^cHigh-comorbidity patients were defined as having a pre-index Quan-CCI score ≥3. ^dHigh-cost patients were defined as those with pre-index all-cause medical costs exceeding the 80th percentile of the cost distribution in the overall IMT COPD population.

Abbreviations: B/F, budesonide/formoterol; CCI, Charlson comorbidity index; COPD, chronic obstructive pulmonary disease; ICD, International Classification of Diseases; FP/SAL, fluticasone propionate/salmeterol; ICS, inhaled corticosteroid; IMT, initial maintenance treatment; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; SITT, single-inhaler triple therapy; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.

Table 1 Pre-Index Patient Characteristics for UMEC/VI versus FP/SAL, B/F, and TIO Matched Cohorts

Characteristics	UMEC/VI vs FP/SAL			UMEC/VI vs B/F			UMEC/VI vs TIO
	UMEC/VI (n=1194)	FP/SAL (n=1194)	Std Diff (%)	UMEC/VI (n=1441)	B/F (n=1441)	Std Diff (%)	UMEC/VI (n=1277)	TIO (n=1277)	Std Diff (%)
Post-index eligibility period, days, mean (SD)	389.7 (303.5)	369.7 (291.6)	6.7	364.0 (292.2)	355.7 (296.6)	2.8	379.1 (301.0)	372.8 (305.2)	2.1
On-treatment follow-up period, days, mean (SD)	144.9 (185.3)	107.5 (153.0)	22.0	139.5 (176.9)	102.5 (139.9)	23.2	143.2 (183.3)	130.3 (167.5)	7.3
Age, years, mean (SD)	72.2 (9.4)	72.1 (10.0)	1.3	72.0 (9.4)	71.9 (9.9)	0.9	72.1 (9.4)	72.1 (9.3)	0.9
Female, n (%)	552 (46.2)	553 (46.3)	0.2	656 (45.5)	636 (44.1)	2.8	570 (44.6)	561 (43.9)	1.4
Region, n (%)
South	638 (53.4)	642 (53.8)	0.7	812 (56.3)	831 (57.7)	2.7	689 (54.0)	667 (52.2)	3.5
West	162 (13.6)	163 (13.7)	0.2	168 (11.7)	160 (11.1)	1.7	169 (13.2)	178 (13.9)	2.1
Midwest	285 (23.9)	280 (23.5)	1.0	331 (23.0)	324 (22.5)	1.2	298 (23.3)	300 (23.5)	0.4
Northeast	108 (9.0)	106 (8.9)	0.6	129 (9.0)	123 (8.5)	1.5	120 (9.4)	131 (10.3)	2.9
Unknown	1 (0.1)	3 (0.3)	4.1	1 (0.1)	3 (0.2)	3.7	1 (0.1)	1 (0.1)	0.0
Insurance plan type, n (%)
Medicare	1032 (86.4)	1020 (85.4)	2.9	1209 (83.9)	1206 (83.7)	0.6	1075 (84.2)	1083 (84.8)	1.7
Commercial	162 (13.6)	174 (14.6)	2.9	232 (16.1)	235 (16.3)	0.6	202 (15.8)	194 (15.2)	1.7
Quan-CCI, mean (SD)	6.2 (2.5)	6.3 (2.5)	3.6	6.1 (2.5)	6.1 (2.5)	0.9	6.1 (2.5)	6.2 (2.5)	1.6
Number of COPD-related exacerbations, mean (SD)
Overall	0.88 (1.02)	0.90 (1.02)	1.6	0.87 (1.00)	0.87 (0.98)	0.3	0.88 (1.01)	0.89 (1.04)	1.4
Moderate	0.34 (0.66)	0.36 (0.74)	3.5	0.36 (0.68)	0.37 (0.73)	1.6	0.35 (0.69)	0.37 (0.75)	1.7
Severe	0.55 (0.75)	0.54 (0.72)	1.1	0.51 (0.72)	0.50 (0.68)	1.2	0.52 (0.73)	0.53 (0.68)	0.2
Patients with COPD-related exacerbations, n (%)
Overall	677 (56.7)	696 (58.3)	3.2	821 (57.0)	833 (57.8)	1.7	725 (56.8)	744 (58.3)	3.0
Moderate	165 (13.8)	182 (15.2)	4.0	234 (16.2)	241 (16.7)	1.3	193 (15.1)	186 (14.6)	1.5
Severe	512 (42.9)	514 (43.0)	0.3	587 (40.7)	592 (41.1)	0.7	532 (41.7)	558 (43.7)	4.1
Respiratory medications, n (%)
Systemic corticosteroids	719 (60.2)	733 (61.4)	2.4	893 (62.0)	909 (63.1)	2.3	778 (60.9)	781 (61.2)	0.5
SABA	494 (41.4)	488 (40.9)	1.0	618 (42.9)	622 (43.2)	0.6	519 (40.6)	532 (41.7)	2.1
SAMA/SABA	186 (15.6)	198 (16.6)	2.7	221 (15.3)	213 (14.8)	1.6	186 (14.6)	180 (14.1)	1.3
Montelukast	58 (4.9)	56 (4.7)	0.8	68 (4.7)	82 (5.7)	4.4	60 (4.7)	52 (4.1)	3.1
SAMA	38 (3.2)	32 (2.7)	3.0	46 (3.2)	31 (2.2)	6.5	40 (3.1)	21 (1.6)	9.7
Methylxanthines	4 (0.3)	5 (0.4)	1.4	4 (0.3)	2 (0.1)	3.0	3 (0.2)	7 (0.5)	5.0
Chronic antibiotic (≥6 months of continuous use)	6 (0.5)	15 (1.3)	8.1	5 (0.3)	14 (1.0)	7.7	7 (0.5)	9 (0.7)	2.0
N-acetylcysteine	2 (0.2)	6 (0.5)	5.8	2 (0.1)	5 (0.3)	4.2	2 (0.2)	5 (0.4)	4.5
PDE-4 inhibitor	1 (0.1)	1 (0.1)	0.0	1 (0.1)	2 (0.1)	2.2	1 (0.1)	3 (0.2)	4.0
COPD-related HCRU^a, mean (SD)
Hospitalizations	0.95 (1.19)	0.94 (0.96)	1.3	0.87 (1.13)	0.88 (1.01)	0.3	0.92 (1.16)	0.92 (0.94)	0.7
ER visits	0.69 (1.72)	0.74 (1.64)	3.1	0.64 (1.62)	0.71 (1.67)	4.6	0.66 (1.67)	0.72 (1.76)	3.4
Outpatient visits	6.4 (11.6)	5.9 (13.5)	3.7	6.5 (12.8)	6.2 (13.4)	2.3	6.5 (13.3)	5.8 (13.2)	5.1
Other visits^b	2.0 (5.0)	2.0 (6.6)	1.5	1.9 (5.1)	1.5 (3.8)	9.3	2.0 (5.2)	1.7 (5.1)	4.3
Medical costs^c, $, mean (SD)
COPD-related total	43,731 (55,663)	43,498 (49,066)	0.4	42,350 (54,206)	42,733 (54,732)	0.7	43,911 (55,865)	45,124 (52,941)	2.2
Hospitalizations	31,602 (50,470)	30,902 (42,715)	1.5	29,716 (48,467)	30,175 (46,161)	1.0	31,249 (50,157)	32,170 (47,696)	1.9
ER visits	4491 (15,154)	4678 (17,315)	1.2	4129 (14,129)	4469 (14,830)	2.3	4330 (14,764)	3932 (12,291)	2.9
Outpatient visits	7084 (17,655)	7434 (21,726)	1.8	8002 (20,452)	7692 (28,620)	1.2	7798 (20,584)	8444 (23,415)	2.9
Other visits^b	554 (5577)	483 (2754)	1.6	503 (5183)	396 (3354)	2.4	534 (5400)	578 (5001)	0.9
All-cause total	113,558 (112,537)	113,968 (106,298)	0.4	113,440 (113,914)	112,781 (107,329)	0.6	111,970 (106,109)	110,769 (104,920)	1.1

Notes: ^aCOPD-related HCRU and costs were defined as claims with a primary or secondary diagnosis of COPD. ^bIncluded visits such as home services and hospice. ^cMedical costs are inflated to 2019 US dollars using the US Medical Care consumer price index from the Bureau of Labor Statistics, US Department of Labor.

Abbreviations: B/F, budesonide/formoterol; COPD, chronic obstructive pulmonary disease; ER, emergency room; FP/SAL, fluticasone propionate/salmeterol; HCRU, healthcare resource use; PDE-4, phosphodiesterase-4; Quan-CCI, Quan-Charlson comorbidity index; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation; Std diff, standardized difference; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.

Table 2 On-Treatment Medical Costs PPPY for UMEC/VI versus FP/SAL, B/F, and TIO Matched Cohorts

	Medical Costs, $^b PPPY, Mean (SD)		Cost Difference (95% CI)	P-value
	UMEC/VI (N=1194)	FP/SAL (N=1194)	–	–
Total COPD-related^a medical costs	28,823 (65,220)	35,411 (92,590)	−6587 (−13,661, −21)	0.048
Hospitalizations	14,961 (47,032)	18,793 (54,422)	−3832 (−8183, 613)	0.072
ER visits	3719 (30,675)	6580 (62,666)	−2862 (−6775, 387)	0.100
Outpatient visits	9360 (28,210)	9254 (35,078)	106 (−3181, 2759)	0.942
Other visits	784 (2849)	784 (2916)	0 (−342, 314)	0.998
Total all-cause medical costs	79,603 (127 705)	94,312 (166 284)	−14,709 (−29,239, 724)	0.060
	UMEC/VI (N=1441)	B/F (N=1441)	–	–
Total COPD-related^a medical costs	30,104 (66,821)	34,737 (80,979)	−4633 (−11,354, 1554)	0.156
Hospitalizations	15,745 (47,196)	18,631 (55,724)	−2887 (−7361, 1685)	0.188
ER visits	3466 (28,689)	4077 (29,383)	−610 (−2106, 1130)	0.401
Outpatient visits	10,141 (31,466)	10,242 (38,813)	−102 (−4191, 3122)	0.906
Other visits	752 (2769)	1787 (28,994)	−1035 (−3148, 167)	0.216
Total all-cause medical costs	87,463 (144 600)	102 158 (186 293)	−14,695 (34,688, 3098)	0.128
	UMEC/VI (N=1277)	TIO (N=1277)	–	–
Total COPD-related^a medical costs	30,022 (66,372)	35,581 (73,944)	−5559 (−11,541, 670)	0.080
Hospitalizations	15,750 (48,130)	20,890 (59,541)	−5140 (−9838, 35)	0.052
ER visits	3619 (29,892)	4411 (17,246)	−793 (−2314, 857)	0.301
Outpatient visits	9866 (28,961)	9598 (33,649)	268 (−2351, 2663)	0.878
Other visits	787 (2879)	681 (3043)	106 (−201, 407)	0.481
All-cause total	85,819 (138,079)	91,161 (156,275)	−5342 (−20,926, 8996)	0.501

Notes: ^aCOPD-related costs were defined as claims with a primary or secondary diagnosis of COPD. ^bMedical costs are inflated to US dollars 2019 using the US Medical Care consumer price index from the Bureau of Labor Statistics from the US Department of Labor.

Abbreviations: B/F, budesonide/formoterol; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ER, emergency room; FP/SAL, fluticasone propionate/salmeterol; PPPY, per patient per year; SD, standard deviation; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.

Figure 3 Kaplan–Meier curves for time-to-first severe exacerbation during the on-treatment period for (A) UMEC/VI versus FP/SAL, (B) UMEC/VI versus B/F, and (C) UMEC/VI versus TIO matched cohorts. ^aNumber of patients still observed at the specific point in time. ^bSevere COPD-related exacerbation defined as an inpatient hospitalization with a diagnosis code for COPD in the primary position.

Abbreviations: B/F, budesonide/formoterol; CI, confidence interval; FP/SAL, fluticasone propionate/salmeterol; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.

Table 3 Rate of on-Treatment COPD-Related Severe Exacerbations for UMEC/VI versus FP/SAL, B/F, and TIO and Matched Cohorts

	Number of Events		Rate (per 100 Person Days)		Rate Ratio (95% CI)	P-value
	UMEC/VI (N=1194)	FP/SAL (N=1194)	UMEC/VI (N=1194)	FP/SAL (N=1194)	–	–
On-treatment period, mean (SD)	144.9 (185.3)	107.5 (153.0)	–	–	–	–
Total person-days	173,045	128,367	–	–	–	–
Severe exacerbations	170	172	0.10	0.13	0.73 (0.59, 0.91)	0.008
	UMEC/VI (N=1441)	B/F (N=1441)	UMEC/VI (N=1441)	B/F (N=1441)	–	–
On-treatment period, mean (SD)	139.5 (176.9)	102.5 (139.9)	–	–	–	–
Total person-days	201,019	147,676	–	–	–	–
Severe exacerbations	203	203	0.10	0.14	0.73 (0.59, 0.93)	0.012
	UMEC/VI (N=1277)	TIO (N=1277)	UMEC/VI (N=1277)	TIO (N=1277)	–	–
On-treatment period, mean (SD)	143.2 (183.3)	130.3 (167.5)	–	–	–	–
Total person-days	182,822	166,413	–	–	–	–
Severe exacerbations	186	205	0.10	0.12	0.83 (0.68, 1.04)	0.080

Abbreviations: B/F, budesonide/formoterol; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FP/SAL, fluticasone propionate/salmeterol; TIO, tiotropium; UMEC/VI, umeclidinium/vilanterol.