The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies

Abstract

Background: Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS(™): COPD) scale (formerly EXACT-RS).

Methods: Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.

Results: Of 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.

Conclusions: Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients' level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms.

Trial registration: ATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 ).

Keywords: Cohort; Exacerbation risk; Morning symptoms; Nighttime symptoms; Prospective; Retrospective.

Figures

Fig. 1

Distribution of E-RS scores at baseline, overall and by pooled GOLD group. n = patients with available data. a RS Total score, ranged 0 to 40. b RS-Breathlessness domain score, range 0 to 17. c RS-Cough & Sputum domain score, range 0 to 11. d RS-Chest Symptoms domain score, range 0 to 12. Higher scores indicate more severe symptoms. E-RS, Evaluating Respiratory Symptoms; GOLD, Global initiative for chronic Obstructive Lung Disease

Fig. 2

Change from baseline in E-RS scores and proportion of E-RS responders at Week 24, overall and by GOLD group a and b RS-Total score; c and d RS-Breathlessness domain; e and f RS-Cough & Sputum domain; g and h RS-Chest Symptoms domain. *p < 0.05, **p < 0.01, ***p < 0.001 vs placebo. Change from baseline data are LS means (SE). Responder data are OR (95 % CI). aplacebo n = 578; aclidinium n = 583; bplacebo n = 72; aclidinium n = 64; cplacebo n = 506; aclidinium n = 519. BID, twice daily; CI, confidence interval; E-RS, Evaluating Respiratory Symptoms; GOLD, Global initiative for chronic Obstructive Lung Disease; LS, least squares; OR, odds ratio; SE, standard error

Fig. 3

Patients with improvement and worsening in RS-Total score, and net treatment benefit at Week 24, overall (a) and by GOLD group (b and c). BID, twice daily; GOLD, Global initiative for chronic Obstructive Lung Disease

Fig. 4

Net treatment benefit for E-RS domain scores at Week 24, overall (a) and by GOLD group (b and c) n = patients with available data. BID, twice daily; E-RS, Evaluating Respiratory Symptoms; GOLD, Global initiative for chronic Obstructive Lung Disease