Applying key learnings from the EMAX trial to clinical practice and future trial design in COPD. (August 2022)

• Record Type: Journal Article
• Authors: Maltais, François; Vogelmeier, Claus F.; Kerwin, Edward M.; Bjermer, Leif H.; Jones, Paul W.; Boucot, Isabelle H.; Lipson, David A.; Tombs, Lee; Compton, Chris; Naya, Ian P.
• Is Part Of: Respiratory medicine. Volume 200(2022)
• Publication Date: 2022-08
• Subjects: Symptomatic COPD -- Low exacerbation risk -- UMEC/VI -- LAMA/LABA -- Long-acting bronchodilators -- GOLD B; AE adverse event -- ATS American Thoracic Society -- CAT COPD Assessment Test -- CI confidence interval -- CID clinically important deterioration -- CII clinically important improvement -- COPD chronic obstructive pulmonary disease -- CTS Canadian Thoracic Society -- EMAX Early MAXimisation of bronchodilation for improving COPD stability -- E-RS Evaluating Respiratory Symptoms COPD -- FEV1 forced expiratory volume in 1 s -- FVC forced vital capacity -- GADS Global Assessment of Disease Severity -- GOLD Global Initiative for Chronic Obstructive Lung Disease -- HRQoL health-related quality of life -- IC inspiratory capacity -- ICS inhaled corticosteroid -- ITT intent-to-treat -- LABA long-acting β2-agonist -- LAMA long-acting muscarinic antagonist -- LS least squares -- NICE National Institute for Health and Care Excellence -- NNT number needed to treat -- OR odds ratio -- PRO patient-reported outcome -- QALY quality-adjusted life-years -- SABA short-acting β2-agonist -- SAC-TDI self-administered computerised-Transition Dyspnoea Index -- SAE serious adverse event -- SAL salmeterol -- SGRQ St George's Respiratory Questionnaire -- UME umeclidinium -- VI vilanterol; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2022.106918
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a large, multicentre, multi-national, randomised, double-blind, 24-week trial. EMAX evaluated the efficacy and safety of dual bronchodilator therapy with umeclidinium bromide (UMEC)/vilanterol (VI) versus monotherapy with either UMEC or salmeterol (SAL) in symptomatic patients with chronic obstructive pulmonary disease (COPD) at low exacerbation risk who were not taking concomitant inhaled corticosteroid (ICS). EMAX generated evidence covering a wide range of patient-centred endpoints in COPD in addition to measures of lung function, clinical deterioration and safety. In addition, prospective and post hoc secondary analyses have generated clinically valuable information regarding the effects of baseline patient characteristics on treatment outcomes. Importantly, as concomitant ICS use was not permitted in this study, EMAX compared dual long-acting muscarinic antagonist (LAMA)/long-acting β2 -agonist (LABA) therapy with LAMA or LABA monotherapy without potential confounding due to concurrent ICS use or withdrawal. EMAX demonstrated beneficial treatment effects of UMEC/VI over UMEC or SAL monotherapy as maintenance treatment across a range of different patient characteristics, with no forfeit in safety. Thus, the trial provided novel insights into the role of LAMA/LABA versus LABA and LAMA monotherapies as maintenance therapy for patients with symptomatic COPD at low risk of exacerbations. This article will explore the clinical implications of the main findings to date of the EMAX trial and consider the key learnings this trial offers for future trial design in COPD. Highlights: EMAX compared dual bronchodilators with monotherapy in symptomatic COPD patients. The study design excluded confounding effects of concomitant ICS treatment. EMAX showed improvements in lung function and symptoms with dual vs monotherapy. Dual therapy was beneficial regardless of smoking status and at CAT scores >10. Dual therapy was cost effective and did not increase adverse events vs monotherapy.