Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?

Abstract

BackgroundAs emphasized by international recommendations and largely confirmed by clinical experience, long-acting bronchodilators play a central role in the maintenance treatment of chronic obstructive pulmonary disease (COPD) due to their proven efficacy in reducing airflow obstruction and improving symptoms.Main bodyThere are some important aspects to define with regard to inhalation therapy for COPD, particularly those concerning the selection criteria and the optimal use of long-acting bronchodilators. First of all, it needs to be determined in which patients and clinical situations monotherapy with one bronchodilator, such as a long-acting muscarinic antagonist (LAMA), should be considered adequate, and in which cases the use of combination therapies, such as the “double bronchodilation” with a LAMA and a long-acting β2-agonist (LABA), should be preferred. Another critical issue concerns the effect of the frequency of daily administration of inhaled agents on the control of symptoms during the 24 h. COPD symptoms are known to exhibit considerable circadian variability with worsening in the early morning, and a significant proportion of patients have disease-related sleep disorders which can adversely affect their quality of life. The worsening of symptoms in the early morning may be due, at least in part, to a reduction in airway caliber caused by an increased “cholinergic tone” at night. As such, the coverage of nighttime and early morning symptoms is a reasonable therapeutic goal, which can be achieved by many patients using LAMAs such as aclidinium bromide twice daily (BID). Therapeutic adherence is known to be a multifactorial phenomenon that is frequently affected by other aspects than dosing frequency, including the technical features and ease of use of the inhalers. To this end, it should be mentioned that certain new-generation inhalers such as Genuair® have been associated in clinical trials with higher patient preference.ConclusionIn this work, in addition to presenting an overview of the main evidence on the efficacy of COPD treatment with the LAMA aclidinium bromide BID, we suggest some selection criteria for the monotherapy with one long-acting bronchodilator or the combination therapy with LAMA and LABA in COPD patients, with particular reference to specific clinical scenarios.

<p>A Real-World Observational Study Examining the Impact of Aclidinium Bromide Therapy on the Quality of Life, Symptoms, and Activity Impairment of Patients with Chronic Obstructive Pulmonary Disease: The Greek ON-AIR Study</p>

“…The circadian variability of COPD symptoms, which may be explained by the circadian modulation of the airway caliber by the cholinergic system, is amply documented. 10,27,28 Accordingly, through their ability to modulate the cholinergic tone, LAMAs constitute especially good therapeutic options for controlling COPD symptoms, with the twice-daily dosing of aclidinium bromide boosting the bronchodilation effect on airways and thus improving the night-time and early-morning symptoms. 10 Moreover, aclidinium-induced improvements in cough and sputum symptoms are supported by its antitussive activity, which is mediated by acid-sensing ion channels and mechanoreceptors.…”

“…10,27,28 Accordingly, through their ability to modulate the cholinergic tone, LAMAs constitute especially good therapeutic options for controlling COPD symptoms, with the twice-daily dosing of aclidinium bromide boosting the bronchodilation effect on airways and thus improving the night-time and early-morning symptoms. 10 Moreover, aclidinium-induced improvements in cough and sputum symptoms are supported by its antitussive activity, which is mediated by acid-sensing ion channels and mechanoreceptors. 26 These characteristics of aclidinium may explain why in a phase IIIb study, aclidinium, but not tiotropium, compared to placebo yielded significant reductions in the severity of night-time and individual early-morning (cough, wheeze, shortness of breath, and phlegm) symptoms, as well as an improvement in activity limitation due to COPD symptoms.…”

“…5 To date, in Europe, it is the only LAMA that can be dosed twice a day. 5,10 The inhalation device of aclidinium bromide is equipped with a safety mechanism to prevent accidental double-dosing, a dose indicator, feedback mechanism for correct inhalation, and a lockout mechanism. The features of the device have been linked with fewer inhalation errors and high patient satisfaction.…”

Daytime symptoms of chronic obstructive pulmonary disease: a systematic review

“…Current COPD treatment decisions (selection of LAMA monotherapy, combination therapy with LAMA/LABA, or add-on therapy with LAMA to LABA/ICS) should be based on individualized assessment, ensuring personalization to the particular needs of the patient. 72,73 Tools and measures to assess daytime COPD symptoms Many different tools have been used to measure and assess daytime symptoms of COPD, not all of which are validated for use in patients with the condition, or specific or focused enough to truly elicit the required information. The E-RS questionnaire, for example, is validated for use in COPD, and was used frequently in the identified clinical studies.…”

Erratum to: Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?

“…In the original publication of this article [ 1 ], the funding section omitted the following information: This work was funded by Momento Medico srl, which has also contributed to the costs for the literature selection and editorial assistance.…”