Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT)

Abstract

BackgroundThe combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).MethodsPatients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.ResultsThe pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).ConclusionsAclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.Trial registrationNCT01462942 and NCT01437397 (ClinicalTrials.gov)Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.

Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

“…В ис следованиях TOnado 1 и TOnado 2 продемонстриро вано снижение числа обострений ХОБЛ на фоне терапии тиотропием / олодатеролом по сравнению с монотерапией олодатеролом (ОР -0,83; 95% ный ДИ -0,71-0,99), но не с тиотропием [95]. В исследо ваниях, посвященных комбинации формотерол / ак лидиний (ФОР / АКЛ) не показано достоверных раз личий по числу обострений между терапией ФОР / АКЛ, монокомпонентами и САЛ / ФЛУ [96][97][98][99]. При терапии комбинацией вилантерол / умеклиди ний также не показано достоверного влияния на риск обострений при сравнении с терапией моно компонентами или тиотропием [100].…”

Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema

“…In a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active-and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT), overall, 55.7% of patients achieved the minimum clinically important difference in TDI focal score with aclidinium, compared with 57.0% with formoterol and 40.3% with placebo [14].…”

“…The pooled analysis of the ATTAIN and AUGMENT studies showed that the percentage of patients achieving a reduction in E-RS total score of ≥2 units was 41.3% with aclidinium, compared with 42.3% with formoterol and 34.4% with placebo [14]. The same pooled analysis documented that improvements in overall night-time symptom severity (aclidinium: -0.16 units; formoterol: −0.19 units) and early-morning symptom severity (aclidinium: −0.14 units; formoterol: −0.17 units) were almost identical [14].…”

The clinical relevance of the emphysema-hyperinflated phenotype in COPD

“…Some also have a positive effect on exacerbation rates, healthcare utilisation and, possibly, mortality [93,94,96,[113][114][115][116][117][118]. One study highlighted the fact that bronchodilators predominantly exert their effects on measures of resting hyperinflation, even when little or no change in FEV1 is observed [37].…”