Efficacy of aclidinium/formoterol 400/12 µg, analyzed by airflow obstruction severity, age, sex, and exacerbation history: pooled analysis of ACLIFORM and AUGMENT

Figures & data

Table 1 Patient demographics and baseline characteristics (pooled safety population)

	Aclidinium/formoterol 400/12 µg (n=720)	Aclidinium 400 µg (n=722)	Formoterol 12 µg (n=716)	Placebo (n=526)	Total (n=2,684)
Age, mean years (SD)	63.4 (8.5)	63.7 (8.5)	63.5 (8.2)	63.7 (8.5)	63.6 (8.4)
≥65 years, n (%)	327 (45.4)	346 (47.9)	337 (47.1)	250 (47.5)	1,260 (46.9)
Male, n (%)	429 (59.6)	444 (61.5)	424 (59.2)	313 (59.5)	1,610 (60.0)
Caucasian, n (%)	672 (93.3)	677 (93.8)	673 (94.0)	500 (95.1)	2,522 (94.0)
Current smoker, n (%)	354 (49.2)	353 (48.9)	350 (48.9)	263 (50.0)	1,320 (49.2)
Mean cigarette consumption, pack-years (SD)	46.6 (25.1)	44.9 (23.7)	45.8 (22.3)	49.1 (26.5)	46.4 (24.3)
Severity of airflow obstruction, n (%)
Stage II (moderate)a	418 (58.1)	410 (57.1)	434 (60.8)	293 (55.9)	1,555 (58.1)
Stage III (severe)b	298 (41.4)	304 (42.3)	275 (38.5)	227 (43.3)	1,104 (41.3)
Baseline FEV1, L (SD)	1.387 (0.524)	1.376 (0.519)	1.397 (0.510)	1.382 (0.550)	1.386 (0.524)
Percent predicted FEV1 at baseline (SD)	48.7 (14.6)	47.9 (13.9)	48.9 (14.3)	47.4 (14.1)	48.3 (14.2)
BDI focal score (SD)	6.4 (2.1)	6.5 (2.1)	6.4 (2.2)	6.5 (2.2)	6.4 (2.2)
Number of exacerbations in previous 12 months, mean (SD)	0.5 (0.9)	0.5 (0.8)	0.4 (0.8)	0.3 (0.7)	0.4 (0.8)
0, n (%)	503 (69.9)	505 (69.9)	509 (71.1)	396 (75.3)	1,913 (71.3)
≥1, n (%)	217 (30.1)	217 (30.1)	207 (28.9)	130 (24.7)	771 (28.7)

Note:

a GOLD Stage II (moderate): FEV₁ ≥50% to <80% predicted and FEV₁/FVC <0.70.¹

b GOLD Stage III (severe): FEV₁ ≥30% to <50% predicted and FEV₁/FVC <0.70.¹

Abbreviations: BDI, Baseline Dyspnea Index; GOLD, Global initiative for chronic Obstructive Lung Disease.

Figure 1 Efficacy endpoints at week 24 analyzed by airflow obstruction severity (moderate vs severe).

Notes: (A) LS mean change from baseline in morning pre-dose (trough) FEV₁;^a (B) LS mean change from baseline in morning 1-hour post-dose FEV ;^{a 1} (C) LS mean TDI focal score;^a (D) HCRU exacerbation rate (moderate/severe) per patient/year;^b and (E) EXACT exacerbation rate per patient/year^b (pooled ITT population). *P<0.05; **P<0.01; and ***P<0.001. ^aAnalysis based on the mixed model for repeated measures. ^bAnalysis based on the negative binomial regression model. Error bars represent 95% CI.
Abbreviations: AB, aclidinium bromide; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FF, formoterol fumarate; HCRU, healthcare resource utilization; ITT, intent-to-treat; LS, least squares; PBO, placebo; TDI, Transition Dyspnea Index.

Figure 2 Efficacy endpoints at week 24 analyzed by patient age (<65 vs ≥65 years).

Notes: (A) LS mean change from baseline in morning pre-dose (trough) FEV₁;^a (B) LS mean change from baseline in morning 1-hour post-dose FEV ;^{a 1} (C) LS mean TDI focal score;^a (D) HCRU exacerbation rate (moderate/severe) per patient/year;^b and (E) EXACT exacerbation rate per patient/year^b (pooled ITT population). *P<0.05; **P<0.01; and ***P<0.001. ^aAnalysis based on the mixed model for repeated measures in pooled ITT population. ^bAnalysis based on the negative binomial regression model. Error bars represent 95% CIs.
Abbreviations: AB, aclidinium bromide; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FF, formoterol fumarate; HCRU, healthcare resource utilization; ITT, intent-to-treat; LS, least squares; PBO, placebo; TDI, Transition Dyspnea Index.

Figure 3 Efficacy endpoints at week 24 analyzed by patient sex.

Notes: (A) LS mean change from baseline in morning pre-dose (trough) FEV₁;^a (B) LS mean change from baseline in morning 1-hour post-dose FEV ;^{a 1} (C) LS mean TDI focal score;^a (D) HCRU exacerbation rate (moderate/severe) per patient/year;^b and (E) EXACT exacerbation rate per patient/year^b (pooled ITT population). *P<0.05; **P<0.01; and ***P<0.001. ^aAnalysis based on the mixed model for repeated measures in pooled ITT population. ^bAnalysis based on the negative binomial regression model. Error bars represent 95% CIs.
Abbreviations: AB, aclidinium bromide; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FF, formoterol fumarate; HCRU, healthcare resource utilization; ITT, intent-to-treat; LS, least squares; PBO, placebo; TDI, Transition Dyspnea Index.

Figure 4 Efficacy endpoints at week 24 analyzed by prior exacerbation history (0 vs ≥1).

Notes: (A) LS mean change from baseline in morning pre-dose (trough) FEV₁;^a (B) LS mean change from baseline in morning 1-hour post-dose FEV ;^{a 1} (C) LS mean TDI focal score;^a (D) HCRU exacerbation rate (moderate/severe) per patient/year;^b and (E) EXACT exacerbation rate per patient/year^b (pooled ITT population). *P<0.05; **P<0.01; and ***P<0.001. ^aAnalysis based on the mixed model for repeated measures in pooled ITT population. ^bAnalysis based on the negative binomial regression model. Error bars represent 95% CIs.
Abbreviations: AB, aclidinium bromide; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FF, formoterol fumarate; HCRU, healthcare resource utilization; ITT, intent-to-treat; LS, least squares; PBO, placebo; TDI, Transition Dyspnea Index.

Global Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease2018 Available from: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdfAccessed October 11, 2018

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.