Current Findings on Fixed Combination Aclidinium/Formoterol in COPD Therapy
The fixed inhalation combination of aclidinium/formoterol represents a combination of a long-acting anticholinergic (LAMA) and a long-acting β2-mimetic (LABA) used for maintenance treatment of moderate to severe chronic obstructive pulmonary disease (COPD). Below, we summarize the current findings on the efficacy and safety of this dual bronchodilation therapy.
Individual Efficacy Parameters
Pulmonary Function
The efficacy of the fixed combination of aclidinium/formoterol in patients with moderate to severe COPD was investigated, among other studies, in phase III studies ACLIFORM COPD and AUGMENT COPD. They confirmed significant improvement in pulmonary function compared to both placebo and monotherapy with aclidinium or formoterol after 24 weeks of therapy. Specifically, FEV1 (forced expiratory volume in one second) was compared before morning inhalation and 1 hour after it, with significant improvement observed in patients on dual bronchodilation therapy. A similar trend, even compared to tiotropium (LAMA), was also demonstrated in the phase III AMPLIFY study.
Reduction of Dyspnea
The ACLIFORM and AUGMENT studies showed a reduction in dyspnea as per the TDI (Transition Dyspnea Index) in patients inhaling the fixed combination of aclidinium/formoterol compared to monotherapy and placebo. In the AMPLIFY study, a reduction in nighttime and early morning COPD symptoms (which are the most bothersome) was also observed, even compared to tiotropium.
Improvement in Quality of Life
The aforementioned studies also highlighted an improvement in quality of life as per the SGRQ (St George's Respiratory Questionnaire) and CAT (COPD Assessment Test) when using the fixed combination of aclidinium/formoterol, though without a significant difference compared to monotherapy and placebo.
Patients included in the phase IV ACTIVATE study additionally noted improvements in endurance during physical activity (+59 seconds) and the number of steps taken per day (+731 steps) after 4 weeks of inhaling the fixed combination of aclidinium/formoterol compared to placebo.
Disease Exacerbation
In the ACLIFORM and AUGMENT studies, fewer COPD exacerbations were reported in patients on dual bronchodilation (who had not had an exacerbation in the past year) compared to placebo (relative risk 0.57; p < 0.01), but not compared to monotherapy. Similar findings were reported in the AMPLIFY study with tiotropium, except for patients on formoterol monotherapy, who had a higher exacerbation rate. In the DETECT observational study, the frequency of exacerbations after 12 months was comparable for patients inhaling aclidinium/formoterol and other LAMA/LABA combinations (glycopyrronium/indacaterol and umeclidinium/vilanterol).
Safety Profile
The safety profile of the fixed combination of aclidinium/formoterol proved comparable to corresponding monotherapies. Additionally, the ASCENT-COPD study found no increased cardiovascular risk or higher incidence of major adverse cardiovascular events (MACE) with aclidinium use compared to placebo over 3 years in patients with concomitant cardiovascular disease or risk factors. The incidence of MACE and mortality were higher in patients with COPD exacerbation in the past year, but not due to the use of LAMA or beta-blockers in medical history. The use of aclidinium, which is characterized by minimal systemic effects, is associated with a low incidence of side effects such as dry mouth and urinary retention.
Conclusion and Discussion
The above studies have demonstrated that the use of the fixed combination of aclidinium/formoterol at a dose of 340 μg/12 μg twice daily in powdered form in patients with moderate to severe COPD is associated with improved pulmonary function and reduced dyspnea compared to placebo, monotherapy, and tiotropium. Additionally, an improvement in quality of life (including exercise tolerance) and a reduction in the number of exacerbations compared to placebo were observed. The majority of patients (78.2–92.0%) found the inhalation system easy or very easy to use.
This fixed combination is indicated if disease control is not achieved with LAMA or LABA monotherapy or if inhaled corticosteroids are unsuitable for the patient (due to side effects or inadequate control). There is also discussion on initiating dual bronchodilation therapy in patients with newly diagnosed COPD. However, clinical studies are needed to identify patients who will benefit from this treatment.
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Source: D’Urzo A. D., Singh D., Donohue J. F. et al. Aclidinium bromide/formoterol fumarate as a treatment for COPD: an update. Expert Rev Respir Med 2021; 15 (9): 1093–1106, doi: 10.1080/17476348.1920403.
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