Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO^® and OTEMTO^® studies: a subgroup analysis by age

Figures & data

Figure 1 OTEMTO^® (1237.5 [NCT1431274] + 1237.6 [NCT1431287]) and TONADO^® (1237.25 [NCT1964352] + 1237.26 [NCT2006732]) study designs.

Note: ^aPrimary end point assessment.
Abbreviations: O, olodaterol; R, randomization; T, tiotropium.

Table 1 Baseline patient demographics by age group

	OTEMTO^® (n=1,609)			TONADO^® (n=5,149)
	40 years to <65 years (n=749)	65 years to <75 years (n=674)	75 years to <85 years (n=186)	40 years to <65 years (n=2,654)	65 years to <75 years (n=1,967)	75 years to <85 years (n=528)
Male, n (%)	428 (57.1)	434 (64.4)	119 (64.0)	1,808 (68.1)	1,499 (76.2)	444 (84.1)
BMI, kg/m^2, mean (SD)	28.2 (6.2)	27.9 (5.5)	27.0 (5.2)	26.0 (6.0)	25.8 (5.1)	25.2 (4.8)
Duration of COPD, years, mean (SD)	6.7 (5.3)	8.5 (5.9)	9.5 (6.5)	5.8 (5.5)	7.2 (6.0)	7.6 (6.4)
Smoking status, n (%)
Ex-smoker	278 (37.1)	423 (62.8)	145 (78.0)	1,345 (50.7)	1,450 (73.7)	446 (84.5)
Current smoker	471 (62.9)	251 (37.2)	41 (22.0)	1,309 (49.3)	517 (26.3)	82 (15.5)
Prebronchodilator screening, mean (SD)
FEV1, L	1.47 (0.53)	1.28 (0.44)	1.11 (0.37)	1.27 (0.54)	1.15 (0.44)	1.09 (0.47)
% of predicted normal FEV1	49.0 (13.4)	47.8 (13.6)	47.5 (13.3)	43.2 (15.6)	43.8 (14.6)	45.9 (14.1)
Postbronchodilator screening, mean (SD)
FEV1, L	1.67 (0.54)	1.46 (0.45)	1.29 (0.37)	1.45 (0.56)	1.31 (0.46)	1.24 (0.39)
% of predicted normal FEV1	55.8 (12.8)	54.3 (12.9)	54.9 (12.4)	49.3 (15.8)	50.1 (14.8)	52.5 (14.1)
GOLD, n (%)a
50% to <80% (GOLD 2)	497 (66.4)	421 (62.5)	116 (62.4)	1,286 (48.5)	989 (50.3)	304 (57.6)
30% to <50% (GOLD 3)	247 (33.0)	249 (36.9)	70 (37.6)	1,011 (38.1)	780 (39.7)	195 (36.9)
<30% (GOLD 4)	4 (0.5)	4 (0.6)	0	354 (13.3)	198 (10.1)	29 (5.5)
Otherb	1 (0.1)	0	0	3 (0.1)	0	0
Baseline pulmonary medications, n (%)
Any	551 (73.6)	532 (78.9)	146 (78.5)	2,033 (76.6)	1,612 (82.0)	452 (85.6)
LAMAs	213 (28.4)	267 (39.6)	73 (39.2)	821 (30.9)	775 (39.4)	238 (45.1)
SAMAs	50 (6.7)	54 (8.0)	19 (10.2)	361 (13.6)	238 (12.1)	66 (12.5)
LABAs	258 (34.4)	285 (42.3)	79 (42.5)	1,194 (45.0)	948 (48.2)	245 (46.4)
SABAs	385 (51.4)	330 (49.0)	94 (50.5)	1,121 (42.2)	768 (39.0)	186 (35.2)
ICS	242 (32.3)	266 (39.5)	93 (50.0)	1,210 (45.6)	977 (49.7)	254 (48.1)
Xanthines	14 (1.9)	17 (2.5)	4 (2.2)	232 (8.7)	218 (11.1)	65 (12.3)

Notes:

a Based on postbronchodilator FEV₁ percentage predicted.

b Of the four patients in this category, three had mild COPD (GOLD 1) and one had missing values.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; GOLD, Global initiative for chronic Obstructive Lung Disease; ICS, inhaled corticosteroids; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting β-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation.

Figure 2 FEV₁ AUC_0–3 response (A) and trough FEV₁ response (B) by age group after 12 weeks (OTEMTO^®) and 24 weeks (TONADO^®).

Abbreviations: AUC_0–3, area under the curve from 0 hour to 3 hours; FEV₁, forced expiratory volume in 1 second; O, olodaterol; SE, standard error; T, tiotropium.

Figure 3 Impact of treatment on FEV₁ AUC_0–3 response (A) and trough FEV₁ response (B) by age group after 12 weeks (OTEMTO^®) and 24 weeks (TONADO^®).

Abbreviations: AUC_0–3, area under the curve from 0 hour to 3 hours; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; O, olodaterol; T, tiotropium.

Table 2 Summary of AEs by age group

System organ class	TONADO^® (n=5,149), n (%)
	40 years to <65 years			65 years to <75 years			75 years to <85 years
	Olodaterol 5 µg	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg	Olodaterol 5 µg	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg	Olodaterol 5 µg	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg
Total patients	520 (100)	540 (100)	525 (100)	408 (100)	383 (100)	407 (100)	107 (100)	106 (100)	96 (100)
All AEs	389 (74.8)	376 (69.6)	379 (72.2)	319 (78.2)	290 (75.7)	305 (74.9)	84 (78.5)	87 (82.1)	77 (80.2)
Serious AEs	84 (16.2)	67 (12.4)	75 (14.3)	65 (15.9)	76 (19.8)	67 (16.5)	29 (27.1)	29 (27.4)	27 (28.1)
Specific AEs with an incidence >3% in total population
Cardiac disorders	24 (4.6)	29 (5.4)	25 (4.8)	29 (7.1)	18 (4.7)	16 (3.9)	5 (4.7)	8 (7.5)	5 (5.2)
Eye disorders	14 (2.7)	10 (1.9)	12 (2.3)	21 (5.1)	21 (5.5)	25 (6.1)	3 (2.8)	7 (6.6)	9 (9.4)
Gastrointestinal disorders	84 (16.2)	72 (13.3)	68 (13.0)	63 (15.4)	63 (16.4)	65 (16.0)	18 (16.8)	18 (17.0)	10 (10.4)
General disorders and administration site conditions	48 (9.2)	50 (9.3)	40 (7.6)	23 (5.6)	38 (9.9)	28 (6.9)	14 (13.1)	10 (9.4)	5 (5.2)
Infections and infestations	191 (36.7)	180 (33.3)	178 (33.9)	155 (38.0)	126 (32.9)	152 (37.3)	46 (43.0)	40 (37.7)	44 (45.8)
Injury, poisoning, and procedural complications	43 (8.3)	41 (7.6)	49 (9.3)	29 (7.1)	29 (7.6)	39 (9.6)	10 (9.3)	13 (12.3)	11 (11.5)
Investigations	23 (4.4)	22 (4.1)	21 (4.0)	23 (5.6)	13 (3.4)	20 (4.9)	5 (4.7)	6 (5.7)	3 (3.1)
Metabolism and nutrition disorders	20 (3.8)	20 (3.7)	22 (4.2)	18 (4.4)	21 (5.5)	19 (4.7)	9 (8.4)	13 (12.3)	7 (7.3)
Musculoskeletal and connective tissue disorders	58 (11.2)	59 (10.9)	84 (16.0)	49 (12.0)	50 (13.1)	54 (13.3)	17 (15.9)	8 (7.5)	18 (18.8)
Neoplasms benign, malignant, and unspecified (including cysts and polyps)	14 (2.7)	8 (1.5)	10 (1.9)	13 (3.2)	20 (5.2)	11 (2.7)	9 (8.4)	9 (8.5)	6 (6.3)
Nervous system disorders	39 (7.5)	47 (8.7)	32 (6.1)	38 (9.3)	42 (11.0)	41 (10.1)	8 (7.5)	12 (11.3)	11 (11.5)
Psychiatric disorders	23 (4.4)	20 (3.7)	13 (2.5)	17 (4.2)	8 (2.1)	14 (3.4)	8 (7.5)	2 (1.9)	7 (7.3)
Renal and urinary disorders	11 (2.1)	13 (2.4)	9 (1.7)	14 (3.4)	16 (4.2)	17 (4.2)	3 (2.8)	7 (6.6)	8 (8.3)
Respiratory, thoracic, and mediastinal disorders	220 (42.3)	222 (41.1)	200 (38.1)	192 (47.1)	162 (42.3)	160 (39.3)	56 (52.3)	55 (51.9)	45 (46.9)
Skin and subcutaneous tissue disorders	19 (3.7)	27 (5.0)	23 (4.4)	28 (6.9)	21 (5.5)	24 (5.9)	7 (6.5)	4 (3.8)	9 (9.4)
Vascular disorders	28 (5.4)	22 (4.1)	28 (5.3)	31 (7.6)	20 (5.2)	24 (5.9)	12 (11.2)	7 (6.6)	10 (10.4)
System organ class	OTEMTO^® (n=1,609), n (%)
	40 years to <65 years			65 years to <75 years			75 years to <85 years
	Placebo	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg	Placebo	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg	Placebo	Tiotropium 5 µg	Tiotropium + olodaterol 5/5 µg
Total patients	183 (100)	185 (100)	189 (100)	183 (100)	174 (100)	158 (100)	37 (100)	43 (100)	55 (100)
All AEs	82 (44.8)	83 (44.9)	76 (40.2)	93 (50.8)	74 (42.5)	71 (44.9)	21 (56.8)	24 (55.8)	30 (54.5)
Serious AEs	6 (3.3)	6 (3.2)	9 (4.8)	9 (4.9)	6 (3.4)	4 (2.5)	0	6 (14.0)	3 (5.5)
Specific AEs with an incidence >3% in total population
Infections and infestations	24 (13.1)	29 (15.7)	28 (14.8)	26 (14.2)	29 (16.7)	27 (17.1)	7 (18.9)	9 (20.9)	6 (10.9)
Nervous system disorders	4 (2.2)	5 (2.7)	1 (0.5)	3 (1.6)	6 (3.4)	9 (5.7)	2 (5.4)	0	3 (5.5)
Respiratory, thoracic, and mediastinal disorders	35 (19.1)	22 (11.9)	24 (12.7)	41 (22.4)	28 (16.1)	26 (16.5)	9 (24.3)	4 (9.3)	13 (23.6)
Gastrointestinal disorders	8 (4.4)	12 (6.5)	15 (7.9)	10 (5.5)	5 (2.9)	6 (3.8)	1 (2.7)	6 (14.0)	1 (1.8)
Musculoskeletal and connective tissue disorders	11 (6.0)	10 (5.4)	12 (6.3)	13 (7.1)	9 (5.2)	16 (10.1)	2 (5.4)	3 (7.0)	5 (9.1)
General disorders and administration site conditions	2 (1.1)	5 (2.7)	8 (4.2)	9 (4.9)	4 (2.3)	4 (2.5)	2 (5.4)	2 (4.7)	3 (5.5)
Injury, poisoning, and procedural complications	3 (1.6)	4 (2.2)	3 (1.6)	8 (4.4)	4 (2.3)	9 (5.7)	2 (5.4)	4 (9.3)	3 (5.5)

Notes: Combined analyses of treated sets. Percentages calculated using total number of patients in the age group with treatment class as the denominator. Medical Dictionary for Regulatory Activities Version 17.1 used for reporting.

Abbreviation: AE, adverse event.