Effect of Fluticasone Propionate/Salmeterol (250/50) on COPD Exacerbations and Impact on Patient Outcomes

Figures & data

Figure 1 Study Flow Diagram.

Table 1 Demography and baseline characteristics

	FSC 250/50	SAL
Characteristic	(N = 394)	(N = 403)
Age, yrs	65.4 ± 9.1	65.3 ± 8.8
Male, %	51	57
Race, %
White	94	95
Black	4	2
Other	4	1
Body Mass Index, kg/m^2	27.6 ± 6.2	27.3 ± 6.6
Current Smoker, %	42	43
Smoking history, pack-yrs	57.8 ± 32.7	56.5 ± 27.8
Pre-bronchodilator FEV1, L	0.97 ± 0.39	0.98 ± 0.37
Pre-bronchodilator FEV1,% predicted	34.1 ± 11.1	33.9 ± 10.6
Post-bronchodilator FEV1, L	1.18 ± 0.51	1.16 ± 0.44
Post-bronchodilator FEV1, % predicted	41.2 ± 14.3	40.0 ± 12.6
Albuterol responsive/non-responsive, %	41/59	37/63
Pre-bronchodilator FVC, L	2.14 ± 0.79	2.14 ± 0.70
Pre-bronchodilator FEV1/FVC	0.46 ± 0.11	0.46 ± 0.11
Previous medication use, %
Ipratropium	5	6
Ipratropium/albuterol combination	33	29
Tiotropium	14	15
Short-acting beta2-agonists	43	45
Long-acting beta2-agonists	8	9
Long-acting beta2-agonists/inhaled corticosteroid combination	44	42
Inhaled corticosteroids	14	14
Theophylline	6	4
Anti-leukotrienes	4	5

FEV₁ = forced expiratory volume in one second; FVC = forced vital capacity; L = Liters.

FSC 250/50 = fluticasone propionate/SAL 250/50 twice daily via the DISKUS.

SAL = salmeterol 50 mcg twice daily via the DISKUS.

All values are presented as absolute numbers or means ± SD.

Table 2 COPD exacerbations

	FSC 250/50	SAL
	(N = 385)	(n = 393)
Subjects with ≥ 1 moderate/severe exacerbation, n (%)	208 (54)	234 (60)
Total number of moderate/severe exacerbations	352	440
Mean annual rate of moderate/severe exacerbations	1.10	1.59
Treatment ratio for FSC 250/50 vs. SAL	0.696
95% confidence interval	0.58, 0.83
p-value	< 0.001
Subjects with ≥ 1 OCS-treated exacerbation, n (%)	161 (42)	197 (50)
Total number of OCS-treated exacerbations	255	332
Mean annual rate of OCS-treated exacerbations	0.81	1.23
Treatment ratio for FSC 250/50 vs. SAL	0.657
95% confidence interval	0.53, 0.81
p-value	< 0.001
Subjects with any exacerbations (mild and moderate/severe)	335 (87)	346 (88)
Total number of all exacerbations	1469	1538
Mean annual rate of all exacerbations	4.67	5.61
Treatment ratio for FSC 250/50 vs. SAL	0.833
95% confidence interval	0.74, 0.94
p-value	0.003
Time to each moderate/severe exacerbation
Hazard ratio for FSC 250/50 vs. SAL	0.730
95% confidence interval	0.617, 0.863
p-value	< 0.001

OCS = oral corticosteroids.

Moderate/severe exacerbations: worsening symptoms requiring treatment with antibiotics, OCS, and/or hospitalization.

Mild exacerbations: worsening symptoms that were self-managed by subject and did not require antibiotic or OCS treatment.

Table 3 Moderate/severe COPD exacerbations by age, reversibility, smoking status, and emphysema (only)

	FSC 250/50 (N = 385)	SAL (N = 393)	Ratio FSC 250/SAL (95% CI)	p-value
Age
< 65 years	n = 177	n = 175
Mean annual rate	1.25	1.55	0.808 (0.620–1.052)	0.113
> 65 years	n = 208	n = 218
Mean annual rate	0.96	1.55	0.621 (0.489–0.788)	< 0.001
Reversibility
Non-reversible	n = 224	n = 245
Mean annual rate	1.17	1.69	0.696 (0.550–0.879)	0.002
Reversible	n = 161	n = 146
Mean annual rate	1.00	1.43	0.695 (0.534–0.905)	0.007
Smoking Status
Current Smoker	n = 164	n = 172
Mean annual rate	1.21	1.46	0.832 (0.647–1.069)	0.151
Former Smoker	n = 221	n = 221
Mean annual rate	1.01	1.69	0.599 (0.468–0.766)	< 0.001
Emphysema Only
Mean annual rate	n = 175	n = 159
	1.08	1.58	0.686 (0.518–0.908)	0.008

Figure 2 Kaplan-Meier Estimates of the Probability of Not Experiencing a Moderate/Severe COPD Exacerbation.

Figure 3 Change from Baseline (randomization) in AM Pre-dose FEV₁ Compared with Screening, over the 52 week Treatment Period, and at Endpoint.

Table 4 Adverse events reported for > 5% of subjects

Adverse Event	FSC 250/50 (N = 394)	SAL (N = 403)
Any event, n (%)	344 (87)	343 (85)
Nasopharyngitis	133 (34)	133 (33)
Pharyngolaryngeal pain	129 (33)	135 (33)
Pyrexia	70 (18)	77 (19)
Headache	52 (13)	53 (13)
COPD	42 (11)	45 (11)
Rhinorrhoea	43 (11)	37 (9)
Upper respiratory tract infection	41 (10)	30 (7)
Nausea	33 (8)	22 (5)
Nasal congestion	32 (8)	22 (5)
Back pain	32 (8)	21 (5)
Diarrhoea	27 (7)	25 (6)
Sinusitis	30 (8)	22 (5)
Chest pain	20 (5)	24 (6)
Muscle spasms	25 (6)	19 (5)
Dizziness	23 (6)	19 (5)
Vomiting	27 (7)	14 (3)
Fatigue	24 (6)	13 (3)
Pneumonia	26 (7)	10 (2)