Early and sustained symptom improvement with umeclidinium/vilanterol versus monotherapy in COPD: a post hoc analysis of the EMAX randomised controlled trial

Abstract

Background: In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown. This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained.

Methods: Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol. Daily Evaluating Respiratory Symptoms in COPD (E-RS:COPD) score and rescue salbutamol use were captured via an electronic diary and analysed initially in 4-weekly periods. Post hoc analyses assessed change from baseline in daily E-RS:COPD score and rescue medication use weekly (Weeks 1-8), and association between E-RS:COPD responder status at Weeks 1-4 and later time points.

Results: In the intent-to-treat population (n = 2425), reductions from baseline in E-RS:COPD scores and rescue medication use were apparent from Day 2 with all treatments. Treatment differences for UMEC/VI versus either monotherapy plateaued by Week 4-8 and were sustained at Weeks 21-24; improvements were consistently greater with UMEC/VI. For all treatments, most patients (60-85%) retained their Weeks 1-4 E-RS:COPD responder/non-responder status at Weeks 21-24. Among patients receiving UMEC/VI who were E-RS:COPD responders at Weeks 1-4, 70% were responders at Weeks 21-24.

Conclusion: Patients with symptomatic COPD had greater potential for early symptom improvements with UMEC/VI versus either monotherapy. This benefit was generally maintained for 24 weeks. Early monitoring of treatment response can provide clinicians with an early indication of a patient's likely longer-term response to prescribed bronchodilator treatment and will facilitate appropriate early adjustments in care.

Clinical trial registration: NCT03034915, 2016-002513-22 (EudraCT Number). The reviews of this paper are available via the supplemental material section.

Keywords: COPD; E-RS:COPD; bronchodilator therapy; rescue medication; symptoms.

Conflict of interest statement

Conflict of interest statement: EMK has served on advisory boards, speaker panels or received travel reimbursement for Amphastar, AstraZeneca, Boehringer Ingelheim, GSK, Mylan, Novartis, Pearl, Sunovion, Teva and Theravance, and has received consulting fees from Cipla and GSK. IHB, DAL, TK and PWJ are employees of GSK and hold stocks and shares in GSK. CFV has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Grifols, Mundipharma, Novartis and the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), and has received personal fees from AstraZeneca, Boehringer Ingelheim, Berlin Chemie/Menarini, Chiesi, Cipla, CSL Behring, GSK, Grifols, MedUpdate, Mundipharma, Novartis, Nuvaira and Teva. FM has received research grants for participating in multicentre trials for AstraZeneca, Boehringer Ingelheim, GSK, Sanofi and Novartis, and has received unrestricted research grants and personal fees from Boehringer Ingelheim, Grifols and Novartis. IPN was an employee of GSK at the time of the study, holds stocks and shares in GSK and is a contingent worker on assignment at AstraZeneca. LT is a contingent worker on assignment at GSK. LB has received honoraria for giving a lecture or attending an advisory board for Airsonett, ALK-Abelló, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Meda, Novartis and Teva.

ELLIPTA and DISKUS are owned by/licensed to the GSK group of companies.

Figures

Figure 1.

Daily mean change from baselinea over time in E-RS:COPD total score (a) and LS mean change from baseline in E-RS:COPD total score (b). aBaseline (Day 0) is defined as the average of the measurements recorded from Day –28 to –1 inclusive. E-RS:COPD, Evaluating Respiratory Symptoms in COPD; LS, least squares; SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.

Figure 2.

E-RS:COPD total score responders (⩾2-point reduction from baseline) CI, confidence interval; E-RS:COPD, Evaluating Respiratory Symptoms in COPD; OR, odds ratio; SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.

Figure 3.

Daily mean change from baseline rescue medication use (puffs/day) (a) LS mean change from baseline rescue medication use (puffs/day) (b). Analyses for Weeks 21–24 were pre-specified, and for Weeks 1, 4 and 8 were conducted post hoc. E-RS:COPD, Evaluating Respiratory Symptoms in COPD; LS, least squares; SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.