Formoterol and Tiotropium Compared With Tiotropium Alone for Treatment of COPD

Figures & data

Figure 1 Study design diagram. BID = twice-daily; FORM = formoterol fumarate; QD = once-daily; TIO = tiotropium bromide; Wk = week.

Figure 2 Timing of spirometry measurements. Spirometry was performed to measure FEV₁ and FVC before and after administration of the first dose of study treatment (A) and before and after doses administered during visits at study weeks 4, 8, and 12 (B). FEV₁ = forced expiratory volume in 1 second; FVC = forced vital capacity.

Table 1 Baseline demographic and disease characteristics (randomized patients)

	FORM + TIO	TIO
	(n = 124)	(n = 131)
Age, y
Mean (SD)	63.8 (8.7)	63.9 (8.5)
Range	42–91	41–82
Sex, n (%)
Women	44 (35)	42 (32)
Men	80 (65)	89 (68)
Race, n (%)
White	111 (90)	124 (95)
Other	13 (10)	7 (5)
Ethnicity, n (%)
Non-Hispanic/non-Latino	123 (99)	130 (99)
Hispanic/Latino	1 (1)	1 (1)
Weight, kg (mean [SD])	79.9 (18.1)	82.4 (19.8)
Height, cm (mean [SD])	171.1 (9.9)	171.5 (10.4)
Current smokers, n (%)	61 (49)	60 (46)
ICS users, n (%)	34 (27)	36 (27)
Shortness of breath, n (%)
Median scores > 2	75 (60)	63 (48)
Median scores < 2	49 (40)	68 (52)
BDI, mean (n)	5.34 (121)	5.67 (125)
FEV1% predicted at screening, n (%)
≥80	1 (1)	0
≥50 and < 80	23 (19)	38 (29)
≥30 and < 50	80 (65)	64 (49)
< 30	20 (16)	28 (21)
Missing values	0	1 (1)

BDI = baseline dyspnea index; FEV₁ = forced expiratory volume in 1 s; FORM = formoterol fumarate 12 μ g BID; ICS = inhaled corticosteroid; SD = standard deviation; TIO = tiotropium bromide 18 μ g QD AM.

Figure 3 Patient disposition. FORM = formoterol fumarate 12 μ g BID; TIO = tiotropium bromide 18 μ g QD.

Figure 4 Improvements by treatment visit in normalized forced expiratory volume in 1 second (FEV₁) area under the response-time curve from 0–4 hours (AUC_0–4h) (A) and normalized forced vital capacity (FVC) AUC_0–4h(B). FORM = formoterol fumarate 12 μ g BID; TIO = tiotropium bromide 18 μ g QD. * p < 0.001 compared with TIO.

Figure 5 Improvements by treatment visit in trough values for forced expiratory volume in 1 second (FEV₁); shown are the averages of values obtained 30 and 10 minutes predose. FORM = formoterol fumarate 12 μ g BID; TIO = tiotropium bromide 18 μ g QD. *p < 0.01; ^†p < 0.001 compared with TIO.

Figure 6 Onset of improvements in postbronchodilator forced expiratory volume in 1 second (FEV₁) following administration of the first dose of each study treatment; the FEV₁ measurement at t = 0 was obtained immediately before administration of FORM + TIO (n = 118) and TIO (n = 125). FORM = formoterol fumarate 12 μ g BID; TIO = tiotropium bromide 18 μ g QD. *p < 0.001; ^† p = 0.005 compared with TIO.

Table 2 Changes from baseline to last visit in patient-centered outcomes

Variables	FORM + TIO	TIO
SGRQ scores	(n = 115)	(n = 128)
Activity	−3.28	−4.76
Impact	−4.31	−3.15
Symptoms	−8.33^a, ^†	−3.97^b
Total	−4.81^a	−3.80
TDI	(n = 121)	(n = 125)
	1.60	1.53
Total COPD symptom scores**	(n = 119)	(n = 129)
AM	−1.13^c, ^†	−0.59
PM	−1.40^†	−0.88
AM/PM average	−1.26^†	−0.73
Rescue medication use	(n = 120)	(n = 128)
AM	−0.45	−0.33
PM	−1.21	−0.84^d
AM/PM average	−0.84	−0.59
Nocturnal awakenings	(n = 117)	(n = 128)
	−0.18	−0.12

^an = 114.

^bn = 129.

^cn = 118.

^dn = 127.

FORM = formoterol fumarate 12 μ g BID; SGRQ = St. George's Respiratory Questionnaire; TDI = transition dyspnea index; TIO = tiotropium bromide 18 μ g QD AM.

*TDI is the sum of three questions scored from −3 = major deterioration to 3 = major improvement. Means are based on an ANCOVA model containing BDI as covariate and extracting variability due to treatment and ICS use at baseline.

**Total COPD symptom scores were the sum of scores for dyspnea (0 = none to 4 = severe), wheezing, cough, and chest tightness (0 = none to 3 = very uncomfortable).

^† p < 0.05 compared with TIO alone.

Table 3 Treatment-emergent adverse events reported by ≥ 3% of patients in either group

	FORM + TIO	TIO
Event, n (%)	(n = 124)	(n = 131)
COPD	16 (13)	12 (9)
Nasopharyngitis	10 (8)	6 (5)
Diarrhea	4 (3)	5 (4)
Cough	4 (3)	4 (3)
Dry mouth	4 (3)	4 (3)
Headache	3 (2)	6 (5)

COPD = chronic obstructive pulmonary disease; FORM = formoterol fumarate 12 μ g BID; TIO = tiotropium bromide 18 μ g QD.