An Evaluation Of Single And Dual Long-Acting Bronchodilator Therapy As Effective Interventions In Maintenance Therapy-Naïve Patients With COPD

Abstract

Background

Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions.

Materials and methods

A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting β₂-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT1462942] and AUGMENT [NCT1437397]).

Results

Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV₁, trough FEV₁, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD.

Conclusion

These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.

Keywords:

• COPD
• treatment-naïve
• LAMA
• LABA

Acknowledgments

Medical writing support, under the direction of the authors, was provided by Nina Divorty, PhD, and Rebecca J. Douglas, PhD, of CMC Connect, a division of McCann Health Medical Communications Ltd., Glasgow, and Macclesfield, UK and was funded by AstraZeneca, Cambridge, UK in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). This work was funded by AstraZeneca, Cambridge, UK, with the original ACLIFORM and AUGMENT studies funded by Almirall S.A. and Forest Laboratories LLC. The sponsors did not place any restriction on authors about the statements made in the final article.

Abbreviations

AB/FF, aclidinium bromide/formoterol fumarate; CAT, COPD Assessment Test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; E-RS, Evaluating Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; LS, least squares; MCID, minimal clinically important difference; mMRC, modified Medical Research Council; OR, odds ratio; PF-10, 10-item Physical Functioning Questionnaire; POET-COPD^®, Prevention Of Exacerbations with Tiotropium in COPD; QoL, quality of life; RCT, randomized controlled trial; SABA, short-acting β₂-agonist; SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index; WPAI, work productivity and activity impairment.

Ethics Approval And Informed Consent

Both the studies included in this post-hoc analysis were conducted in accordance with the Declaration of Helsinki, International Council for Harmonisation/Good Clinical Practice Guidelines, and local regulations. The regulatory authorities approved the protocols for each country and each center had an independent ethics committee.

Data Availability

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

DS is supported by the NIHR Manchester Biomedical Research Centre; and has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards and research grants from various pharmaceutical companies including Apellis, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici S.p.A, Cipla, Genentech, GlaxoSmithKline, Glenmark, Johnson & Johnson, Mundipharma, Novartis, Peptinnovate Ltd., Pfizer Inc, Pulmatrix, Skyepharma, Teva, Theravance Biopharma, Menarini, and Verona Pharma. ADD has received research, consulting, and lecturing fees from Almirall, Altana, AstraZeneca, Boehringer Ingelheim (Canada) Ltd, Forest Laboratories, GlaxoSmithKline, KOS Pharmaceuticals, Merck Canada, Methapharm, Novartis Canada/USA, ONO Pharmaceutical Co., Pfizer Canada, Schering-Plough, Sepracor, and SkyePharma.

JFD has received consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, GSK, Mylan, Theravance, and Sunovion. He is a member of the Data Monitoring Committee for AstraZeneca.

EMK has participated in consulting, advisory boards, speaker panels, or received travel reimbursement from Amphastar Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Cipla, Chesi, Forest Laboratories LLC, GSK, Mylan, Novartis, Oriel, Pearl, Sunovion, Teva Pharmaceutical Industries Ltd., and Theravance Biopharma. He has conducted multicenter clinical research trials for ~40 pharmaceutical companies. EM, FC, and DJ are employees of AstraZeneca and former employees of Almirall S.A., Barcelona, Spain. AR is a former employee of Almirall S.A., Barcelona, Spain and was an employee of AstraZeneca at the time the study was conducted. The authors report no other conflicts of interest in this work.