Real-world effectiveness of umeclidinium/vilanterol versus fluticasone propionate/salmeterol as initial maintenance therapy for chronic obstructive pulmonary disease (COPD): a retrospective cohort study

Figures & data

Figure 1 Study design.

Abbreviations: FP/SAL, fluticasone propionate/salmeterol; UMEC/VI, umeclidinium/vilanterol.

Table 1 Pre-index patient demographics and clinical characteristics before and after inverse probability of treatment weighting

Demographics	Pre-IPTW				Post-IPTW
	UMEC/VI (N=1386)	FP/SAL (N=3920)	Standard difference (%)	P-value	UMEC/VI (N=1386)	FP/SAL (N=3920)	Standard difference (%)	P-value
Age, years, mean (SD)	68.52 (10.48)	69.49 (10.49)	−9.30	0.003	69.47 (10.59)	69.15 (10.53)	3.04	0.497
Male, %	54.69	46.38	16.68	<0.001	49.01	48.50	1.02	0.823
Geographic region, %
Northeast	14.43	17.70	−8.92	0.005	17.23	16.88	0.95	0.845
Midwest	26.77	31.63	−10.72	<0.001	30.62	30.29	0.72	0.878
South	51.37	41.10	20.72	<0.001	42.28	43.73	−2.93	0.510
West	7.43	9.57	−7.66	0.017	9.86	9.10	2.60	0.620
Insurance type, %
Commercial	33.62	24.06	21.23	<0.001	26.94	26.76	0.40	0.920
MAPD	66.38	75.94	−21.23	<0.001	73.06	73.24	−0.40	0.920
Charlson comorbidity score
Mean (SD)	2.16 (1.66)	2.33 (1.78)	−10.07	0.001	2.31 (1.77)	2.30 (1.78)	0.42	0.928
Chronic disease score
Mean (SD)	5,077.14 (3,743.13)	5,316.92 (3,632.34)	−6.50	0.036	5,358.00 (3,964.69)	5,225.13 (3,620.08)	3.50	0.496
Median	4,272.00	4,636.00			4,596.00	4,596.00
COPD severity score
Mean (SD)	23.86 (5.27)	24.04 (5.80)	−3.15	0.301	24.21 (4.97)	23.98 (6.03)	4.06	0.267
Median	23.37	23.31			24.18	23.29
Moderate/severe COPD exacerbations pre-index, %	33.19	30.26	6.31	0.042	32.83	31.15	3.61	0.409
COPD-related healthcare resource utilization
Ambulatory visits, %	77.78	63.37	32.02	<0.001	70.35	67.41	6.35	0.197
ED visits, %	8.59	8.01	2.09	0.501	8.62	8.30	1.15	0.781
Inpatient visits, %	6.13	6.96	−3.36	0.289	7.16	6.81	1.37	0.763
Medical costs ($), mean (SD)	1,301.96 (5,387.25)	1,965.51 (9,398.59)	−8.66	0.001	1,466.79 (5,806.35)	1,950.14 (9,434.29)	−6.17	0.114
All-cause healthcare costs, mean (SD)	16,195.32 (26,647.25)	18,232.19 (32,821.94)	−6.81	0.022	16,556.59 (25,056.32)	18,130.01 (33,271.90)	−5.34	0.128
COPD medications, %
Systemic corticosteroids	48.56	47.88	1.35	0.666	47.63	48.06	−0.87	0.849
SAMA	2.09	2.93	−5.38	0.098	2.55	2.87	−2.02	0.645
SABA	49.13	54.52	−10.79	<0.001	54.00	53.37	1.27	0.780
SAMA/SABA combination	13.85	17.02	−8.76	0.006	17.04	16.21	2.21	0.662

Abbreviations: CDS, chronic disease score; COPD, chronic obstructive pulmonary disease; ED, emergency department; FP/SAL, fluticasone propionate/salmeterol; IPTW, inverse probability of treatment weighting; MAPD, Medicare advantage plan D; SD, standard deviation; PDE-4, phosphodiesterase-4; SABA, short-acting β₂-antagonist; SAMA, short-acting muscarinic antagonist; UMEC/VI, umeclidinium/vilanterol.

Figure 2 Patient identification and attrition.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; FP/SAL, fluticasone propionate/salmeterol; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; UMEC/VI, umeclidinium/vilanterol.

Figure 3 Medication adherence. (A) Mean PDC. (B) Percentage of patients achieving PDC≥80.

Note:  Error bars indicate the standard deviation.
Abbreviations: FP/SAL, fluticasone propionate/salmeterol; PDC, proportion of days covered; UMEC/VI, umeclidinium/vilanterol.

Figure 4 Kaplan–Meier curves for incidence of moderate/severe exacerbations. (A) Intent-to-treat analysis. (B) On-treatment sensitivity analysis.

Abbreviations: FP/SAL, fluticasone propionate/salmeterol; UMEC/VI, umeclidinium/vilanterol.

Figure 5 Kaplan–Meier curve for incidence of multiple-inhaler triple therapy.

Abbreviations: FP/SAL, fluticasone propionate/salmeterol; UMEC/VI, umeclidinium/vilanterol.

Table S1 Variables included in inverse probability of treatment weighting model

Variable category	Variable
Demographics	Index month/year (categorical) Age in years (categorical) Gender Region Health plan type Business line (commercial or MAPD) Pharmacy plan type: Enhanced alternative, Employer group
Clinical characteristics and comorbidities	COPD severity score Charlson comorbidity index (categorical) AHRQ-defined comorbidities Hypertension Other lower respiratory disease Disorders of lipid metabolism Diseases of the heart Diseases of the urinary system Other connectivity tissue disease Non-traumatic joint disorder Respiratory infection Screening and history of mental health and substance abuse
COPD exacerbation	COPD exacerbation (moderate/severe) Severe COPD exacerbation
Respiratory medication use	SAMA units (categorical) SAMA/SABA inhaled units (categorical) Count of SABA fills (categorical) CTR (categorical) CTR non-missing flag Methylxanthines use SAMA/SABA use Index fill ≥90-day fill OCS use
All-cause and COPD-related healthcare utilization and costs	All-cause ambulatory count (categorical) All-cause inpatient count (categorical) All-cause medical costs (categorical) COPD-related ambulatory cost (categorical) Index prescription patient-paid costs (categorical) COPD-related inpatient stay

Abbreviations: AHRQ, agency for healthcare research and quality; COPD, chronic obstructive pulmonary disease; CTR, COPD treatment ratio; MAPD, medicare advantage Part D; OCS, oral corticosteroids; SABA, short-acting β₂-antagonist; SAMA, short-acting muscarinic agonist.

Table S2 Post-inverse probability of treatment weighting post-index time to first occurrence of multiple-inhaler triple therapy (intent-to-treat) – proportional hazard model, first 90 days and 91─365 days

Independent variables	Hazard ratio (95% CI)	P-value
UMEC/VI vs FP/SAL over time
First 90 days	0.408 (0.247, 0.674)	<0.001
91─365 days	0.878 (0.580, 1.329)	0.539
Baseline medication units
Methylxanthines units	1.093 (0.362, 3.304)	0.874
SAMA nebulized units	0.526 (0.167, 1.662)	0.274
SAMA/SABA combination inhaled units
1	reference	–
2─5	1.109 (0.438, 2.808)	0.828
6─10	1.805 (0.399, 8.163)	0.443
10+	2.106 (0.631, 7.027)	0.226
0	1.155 (0.563, 2.371)	0.694
All cause inpatient costs, %
≤50	reference	–
>50–≤75	1.381 (0.430, 4.436)	0.587
>75	1.239 (0.975, 1.574)	0.080
All cause other medical costs, %
≤25	reference	–
>25–≤50	1.009 (0.750, 1.359)	0.950
>50–≤75	1.111 (0.809, 1.527)	0.514
>75	1.152 (0.867, 1.530)	0.331

Abbreviations: CI, confidence interval; FP/SAL, fluticasone propionate/salmeterol; SABA, short-acting β₂-antagonist; SAMA, short-acting muscarinic-antagonist; UMEC/VI, umeclidinium/vilanterol.

Table S3 Secondary outcome: post-inverse probability of treatment weighting post-index time to first occurrence of multiple-inhaler triple therapy (intent-to-treat) – proportional hazard model, monthly time increments

Independent variables	Hazard ratio (95% CI)	P-value
UMEC/VI vs FP/SAL over time, days
1–30	0.314 (0.188, 0.521)	<0.001
31–60	1.020 (0.346, 3.003)	0.971
61–90	0.222 (0.057, 0.861)	0.030
91–120	1.859 (0.858, 4.028)	0.116
121–150	0.493 (0.177, 1.372)	0.176
151–180	0.669 (0.200, 2.233)	0.513
181–210	0.509 (0.186, 1.397)	0.190
211–240	1.737 (0.638, 4.735)	0.280
241–270	0.772 (0.221, 2.693)	0.684
271–300	1.027 (0.219, 4.812)	0.973
301–330	0.550 (0.189, 1.602)	0.273
331–365	0.274 (0.090, 0.830)	0.022
Baseline medication units
Methylxanthines units	1.093 (0.362, 3.302)	0.874
SAMA nebulized units	0.526 (0.167, 1.662)	0.274
SAMA/SABA combination inhaled units
1	reference	–
2─5	1.108 (0.438, 2.807)	0.828
6─10	1.806 (0.398, 8.194)	0.444
10+	2.105 (0.632, 7.015)	0.226
0	1.155 (0.563, 2.371)	0.694
All cause inpatient costs, %
≤50	reference	–
>50–≤75	1.383 (0.430, 4.449)	0.586
>75	1.238 (0.975, 1.574)	0.080
All-cause other medical costs
0%≤ Other medical cost ≤ 25%	reference	–
25%< Other medical cost ≤ 50%	1.010 (0.750, 1.359)	0.950
50%< Other medical cost ≤ 75%	1.112 (0.809, 1.527)	0.514
75%< Other medical cost	1.152 (0.867, 1.530)	0.330

Abbreviations: CI, confidence interval; FP/SAL, fluticasone propionate/salmeterol; SABA, short-acting beta antagonist; SAMA, short-acting muscarinic-antagonist; UMEC/VI, umeclidinium/vilanterol.