Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial.

Szczegóły
Abstrakt

Tytuł:: Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial.
Autorzy:: Vogelmeier CF; Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps-Universität Marburg, German Centre for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany. .
Jones PW; GSK, Brentford, Middlesex, UK.
Kerwin EM; Altitude Clinical Consulting and Clinical Research Institute of Southern Oregon, Medford, OR, USA.
Boucot IH; GSK, Brentford, Middlesex, UK.
Maltais F; Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada.
Tombs L; Precise Approach Ltd, GSK, Brentford, Middlesex, UK.
Compton C; GSK, Brentford, Middlesex, UK.
Lipson DA; Respiratory Clinical Sciences, GSK, Collegeville, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bjermer LH; Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
Źródło:: Respiratory research [Respir Res] 2021 Oct 28; Vol. 22 (1), pp. 279. Date of Electronic Publication: 2021 Oct 28.
Typ publikacji:: Journal Article; Multicenter Study; Randomized Controlled Trial
Język:: English
Imprint Name(s):: Publication: 2001- : London : BioMed Central Ltd.
Original Publication: London : Current Science Ltd., c2000-
MeSH Terms:: Adrenergic beta-2 Receptor Agonists/*administration & dosage
Benzyl Alcohols/*administration & dosage
Bronchodilator Agents/*administration & dosage
Chlorobenzenes/*administration & dosage
Lung/*drug effects
Muscarinic Antagonists/*administration & dosage
Pulmonary Disease, Chronic Obstructive/*drug therapy
Quinuclidines/*administration & dosage
Adrenergic beta-2 Receptor Agonists/adverse effects ; Aged ; Benzyl Alcohols/adverse effects ; Bronchodilator Agents/adverse effects ; Chlorobenzenes/adverse effects ; Double-Blind Method ; Drug Combinations ; Female ; Forced Expiratory Volume ; Humans ; Lung/physiopathology ; Male ; Middle Aged ; Muscarinic Antagonists/adverse effects ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Quinuclidines/adverse effects ; Recovery of Function ; Time Factors ; Treatment Outcome
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Calverley PM, Albert P, Walker PP. Bronchodilator reversibility in chronic obstructive pulmonary disease: use and limitations. Lancet Respir Med. 2013; 1(7): 564–73.
Hansen JE, Porszasz J. Counterpoint: is an increase in FEV1 and/or FVC ≥ 12% of control and ≥ 200 mL the best way to assess positive bronchodilator response? No. Chest. 2014;146(3):538–41. (PMID: 10.1378/chest.14-0437)
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021. https://goldcopd.org/wp-content/uploads/2019/12/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf . Accessed Dec 2020.
Janson C, Malinovschi A, Amaral AFS, et al. Bronchodilator reversibility in asthma and COPD: findings from three large population studies. Eur Respir J. 2019;54(3):1900561. (PMID: 10.1183/13993003.00561-2019)
Ohar JA, Bowling A, Goodin T, et al. Efficacy and safety of glycopyrrolate in patients with COPD by reversibility: pooled analysis of GEM1 and GEM2 12-week studies. Int J Chron Obstruct Pulmon Dis. 2019;14:461–70. (PMID: 10.2147/COPD.S194102)
Ohar JA, Sharma S, Goodin T, et al. Efficacy of indacaterol/glycopyrrolate in patients with COPD by airway reversibility at baseline: a pooled analysis of the FLIGHT1 and FLIGHT2 12-week studies. COPD. 2019;16(2):133–9. (PMID: 10.1080/15412555.2019.1612341)
Tashkin D, Kesten S. Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses. Chest. 2003;123(5):1441–9. (PMID: 10.1378/chest.123.5.1441)
Hanania NA, Sharafkhaneh A, Celli B, et al. Acute bronchodilator responsiveness and health outcomes in COPD patients in the UPLIFT trial. Respir Res. 2011;12(1):6. (PMID: 10.1186/1465-9921-12-6)
Maltais F, Bjermer L, Kerwin EM, et al. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019;20(1):238. (PMID: 10.1186/s12931-019-1193-9)
Dorinsky PM, Reisner C, Ferguson GT, Menjoge SS, Serby CW, Witek TJ Jr. The combination of ipratropium and albuterol optimizes pulmonary function reversibility testing in patients with COPD. Chest. 1999;115(4):966–71. (PMID: 10.1378/chest.115.4.966)
Donohue JF. Minimal clinically important differences in COPD lung function. COPD. 2005;2(1):111–24. (PMID: 10.1081/COPD-200053377)
Mahler DA, Witek TJ Jr. The MCID of the transition dyspnea index is a total score of one unit. COPD. 2005;2(1):99–103. (PMID: 10.1081/COPD-200050666)
Leidy NK, Murray LT, Monz BU, et al. Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials. Respir Res. 2014;15:124. (PMID: 10.1186/s12931-014-0124-z)
Grant Information:: 201749 [NCT03034915] GSK
Contributed Indexing:: Keywords: Bronchodilator reversibility; COPD; Dual bronchodilators; E-RS; Lung function; Rescue medication; SAC-TDI; Umeclidinium/vilanterol
Substance Nomenclature:: 0 (Adrenergic beta-2 Receptor Agonists)
0 (Benzyl Alcohols)
0 (Bronchodilator Agents)
0 (Chlorobenzenes)
0 (Drug Combinations)
0 (GSK573719)
0 (Muscarinic Antagonists)
0 (Quinuclidines)
028LZY775B (vilanterol)
Entry Date(s):: Date Created: 20211029 Date Completed: 20220207 Latest Revision: 20220317
Update Code:: 20240105
PubMed Central ID:: PMC8555352
DOI:: 10.1186/s12931-021-01859-w
PMID:: 34711232
: Czasopismo naukowe

Pełny tekst

Background: In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids.
Methods: The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV 1 ) of ≥ 12% and ≥ 200 mL 10-30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV 1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21-24, and rescue medication use (puffs/day) over Weeks 1-24. Analyses were conducted across the full range of reversibility (-850-896 mL); however, results are presented for the range -100-400 mL because there were few participants with values outside this range.
Results: The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV 1 , SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV 1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range.
Conclusions: FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.
(© 2021. The Author(s).)

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