The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life. This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.

Methods: Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7. Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.

Results: Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male). In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05). Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients. Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05). Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001). In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05). The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.

Conclusion: Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used. Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms.

Keywords: COPD; aclidinium; dyspnea; formoterol; lung function; symptoms.

Figure 1

One-hour morning postdose FEV₁ change from baseline in less symptomatic and more symptomatic patients with COPD at week 24. Notes: Data are LS mean ± SE for the pooled ITT population; ***P<0.0001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; FF, formoterol fumarate 12 µg; LS, least squares; ITT, intent-to-treat; SE, standard error.

Figure 2

Trough FEV₁ (1-hour morning predose) change from baseline in less symptomatic and more and symptomatic patients with COPD at week 24. Notes: Data are LS mean ± SE for the pooled ITT population; *P<0.05; ***P<0.001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; FF, formoterol fumarate 12 µg; ITT, intent-to-treat; LS, least squares; SE, standard error.

Figure 3

TDI focal score change from baseline in less symptomatic and more symptomatic patients with COPD at week 24. Notes: Data are LS mean ± SE for the pooled ITT population; *P<0.05; ***P<0.001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FF, formoterol fumarate 12 µg; ITT, intent-to-treat; LS, least squares; SE, standard error; TDI, Transition Dyspnea Index.

Figure 4

E-RS total score change from baseline in less symptomatic and more symptomatic patients with COPD at week 24. Notes: Data are LS mean ± SE for the pooled ITT population; *P<0.05; **P<0.01; ***P<0.001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FF, formoterol fumarate 12 µg; ITT, intent-to-treat; LS, least squares; SE, standard error.

Figure 5

Change from baseline in (A) early-morning and (B) nighttime symptom severity in less symptomatic and more symptomatic patients with COPD at week 24. Notes: Data are LS mean ± SE for the pooled ITT population; *P<0.05; **P≤0.01; ***P<0.001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FF, formoterol fumarate 12 µg; ITT, intent-to-treat; LS, least squares; SE, standard error.

Figure 6

Change from baseline in early-morning limitation of activity in (A) the overall pooled population and (B) less symptomatic and more symptomatic patients with COPD. Notes: Data are LS mean ± SE for the pooled ITT population; *P<0.05; **P<0.01; ***P<0.001. Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FF, formoterol fumarate 12 µg; ITT, intent-to-treat; LS, least squares; SE, standard error.

Figure 7

Rate of moderate or severe COPD exacerbations (HCRU criteria) in less symptomatic and more symptomatic patients at Week 24, (A) less symptomatic and more symptomatic defined by E-RS score, (B) less symptomatic and more symptomatic defined by BDI score. Note: *P≤0.05; P=0.057 vs placebo in more symptomatic patients with BDI <7; Moderate or severe exacerbations are defined as exacerbations that require treatment with antibiotics or corticosteroids and those which result in hospitalization, respectively; Exacerbations data are RR (95% CI). Abbreviations: AB, aclidinium bromide 400 µg; BDI, Baseline Dyspnea Index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FF, formoterol fumarate 12 µg; HCRU, healthcare resource utilization; RR, rate ratio.