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Randomized Controlled Trial
. 2021 May 3:16:1215-1226.
doi: 10.2147/COPD.S295835. eCollection 2021.

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement

Claus F Vogelmeier  1 , Ian P Naya  2   3 , François Maltais  4 , Leif Bjermer  5 , Edward M Kerwin  6 , Lee Tombs  7 , Paul W Jones  2 , Chris Compton  2 , David A Lipson  8   9 , Isabelle H Boucot  2   10
Affiliations
Randomized Controlled Trial

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement

Claus F Vogelmeier et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Introduction: This post hoc analysis of the "Early MAXimization of bronchodilation for improving COPD stability" (EMAX) trial investigated whether patients achieving early clinically important improvement (CII) sustained longer-term improvements and lower risk of clinically important deterioration (CID).

Methods: Patients were randomized to umeclidinium/vilanterol, umeclidinium, or salmeterol for 24 weeks. The patient-reported outcomes (PROs) Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms, St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) were assessed. CII, defined as attaining minimum clinically important differences (MCID) in ≥2 PROs, was assessed at Weeks 4, 12 and 24. CID was defined as a deterioration in CAT, SGRQ, TDI by the MCID and/or a moderate/severe exacerbation from Day 30.

Results: Of 2425 patients, 50%, 53% and 51% achieved a CII at Weeks 4, 12 and 24, respectively. Patients with a CII at Week 4 versus those without had significantly greater odds of achieving a CII at Weeks 12 and 24 (odds ratio: 5.57 [95% CI: 4.66, 6.66]; 4.09 [95% CI: 3.44, 4.86]). The risk of a CID was higher in patients who did not achieve a CII at Week 4 compared with patients who did (hazard ratio [95% CI]: 2.09 [1.86, 2.34]). Patients treated with umeclidinium/vilanterol versus either monotherapy had significantly greater odds of achieving CII at Weeks 4, 12 and 24.

Conclusion: Achieving a CII at Week 4 was associated with longer-term improvement in PROs and a reduced risk of deterioration. Further research is required to investigate the importance of an early response to treatment on the long-term disease course.

Keywords: COPD symptoms; bronchodilator; clinically important deterioration; clinically important improvement; early improvement; patient-reported outcomes.

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Conflict of interest statement

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, CSL Behring, GSK, Grifols, MedUpdate, Nuvaira, Novartis and Teva. 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, Connect Biopharma, and GSK. IHB, DAL, CC and PWJ are employees of GSK and hold stock and shares in GSK. FM has received research grants for participating in multicenter trials for AstraZeneca, Boehringer Ingelheim, GSK, Sanofi and Novartis, and has received unrestricted research grants and personal fees from Boehringer Ingelheim, Grifols and Novartis. FM also reports financial participation in Oxynov, a company which is developing an oxygen delivery system. IPN was an employee of GSK at the time of the study, holds stocks and shares in GSK, and was 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. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Proportion of patients achieving a CII at Weeks 12 and 24 stratified by the achievement of a CII at Week 4.
Figure 2
Figure 2
Proportion of patients with a Clinically Important Deterioration (CID)a after Day 30 by: (A) achievement of a CII at Week 4; (B) the number of PRO responses at Week 4; (C) Kaplan–Meier curve of time to first CID in patients by achievement of CII at Week 4.
Figure 3
Figure 3
Proportion of patients achieving CII (reaching MCID in at least two PROs) at Weeks 4, 12 and 24a.
See this image and copyright information in PMC

References

    1. Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:95–99. doi:10.2147/COPD.S27480 - DOI - PMC - PubMed
    1. Sun Y, Zhou J. New insights into early intervention of chronic obstructive pulmonary disease with mild airflow limitation. Int J Chron Obstruct Pulmon Dis. 2019;14:1119–1125. doi:10.2147/COPD.S205382 - DOI - PMC - PubMed
    1. Sutherland ER, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2689–2697. doi:10.1056/NEJMra030415 - DOI - PubMed
    1. Decramer M, Celli B, Kesten S, Lystig T, Mehra S, Tashkin DP. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet. 2009;374(9696):1171–1178. doi:10.1016/s0140-6736(09)61298-8 - DOI - PubMed
    1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease; 2021. Accessed January 2021. - PubMed

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