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Is initial maintenance treatment with LAMA/LABAs beneficial for patients with moderate COPD symptoms?

Explore the evidence for initial maintenance treatment with dual bronchodilators compared with bronchodilator monotherapy

LAMA/LABAs versus monotherapy

For patients with COPD with dyspnoea or exercise intolerance, LAMA/LABA combination therapy is recommended over LABA or LAMA monotherapy in the ATS guidelines for COPD management.1 However, the GOLD strategy only recommends initiating maintenance treatment with LAMA/LABA in patients with a history of exacerbations who are highly symptomatic (CAT score more than 20).2

Explore the efficacy and safety data for LAMA/LABAs versus monotherapy using the evidence from a meta-analysis of 23 RCTs with over 27,000 patients:3

  • Efficacy

    Overall, treatment with LAMA/LABA is associated with a greater improvement in outcomes, including lung function, symptoms, exacerbations and quality of life, over 6 months versus LAMA or LABA alone.3

    Forest-plot-showing-greater-improvement-in-lung-function, symptoms,-exacerbations-and-quality-of-life,-over-6-months-with LAMA/LABA-versus-LAMA-or-LABA

    This figure is adapted and reproduced with the permission of BMJ Journals. It was first published in Oba Y, et al. Thorax. 2016;71:15–25

  • Safety

    The benefits of LAMA/LABA versus LAMA or LABA alone are achieved without an apparent increase in adverse events.3

    Hazard-ratios-for-adverse-events-of-LAMA/LABA-vs-LAMA-or-LABA

    The figure has been independently created by GSK from original data first published in Oba Y, et al. Thorax. 2016;71:15–25

Although multiple studies have demonstrated greater clinical improvements and comparable safety profiles with LAMA/LABAs versus monotherapy, discussion continues as to the optimum use of dual bronchodilators, particularly when considered as initial maintenance therapy. Challenges and questions relating to the benefit and risk of each class have now been appropriately addressed by the Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial (ITT population: N=2425).

The EMAX trial

The EMAX trial was a large 24-week randomised, double-blind, double-dummy, parallel-group trial of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg (QD), versus UMEC 62.5 µg (QD) and salmeterol (SAL) 50 µg (BID).4

It was the first RCT to assess the efficacy and safety of a LAMA/LABA in symptomatic patients with a low risk of exacerbation who were not using ICS.4

  • Learn more

    ≥6-month efficacy trials with LAMA/LABA versus monotherapy

    Baseline-ICS-use-and-lung-function-in-trials-of-LAMA/LABAs-vs- monotherapy

    The figure has been independently created by GSK

Study-population

Study population

  • Age ≥40 years
  • CAT ≥10
  • Post-bronchodilator FEV1 30–80%
  • ≤1 moderate exacerbation in the previous year
  • Not receiving ICS, LAMA/LABA
Endpoints

Endpoints

  • Primary endpoint: trough FEV1 at Week 24
  • Key secondary endpoint: SAC-TDI (trial powered for SAC-TDI)
  • Other secondary endpoints include: daily symptoms E-RS, rescue medication use, CAT, SGRQ, time to first exacerbation, time to first CID
  • Safety
Topline-results

Topline results

  • At Week 24, change from baseline in lung function (trough FEV1, FVC and IC) was significantly greater with UMEC/VI versus both UMEC and SAL4
  • At Week 24, change in SAC-TDI, E-RS and the number of rescue medication-free days were significantly improved with UMEC/VI versus both UMEC and SAL4

Post hoc fractional polynomial analysis by baseline symptom severity

Patients receiving UMEC/VI had numerically greater improvements in breathlessness compared with patients receiving UMEC, regardless of symptom severity.11

This suggests that dual bronchodilation may be considered as appropriate initial therapy for patients with COPD across a broad range of symptom severities, not only those with severe symptoms (CAT ⩾20).11

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Improvement in symptoms

Greater sustained improvements in symptoms with UMEC/VI versus monotherapy were statistically significant from Week 1, and were generally sustained over 24 weeks.12

Improvements-in-E-RS score-with-UMEC/VI-versus-monotherapy from-Week-1-to-Week-24

Figure adapted with permission from Kerwin EM, et al. Ther Adv Respir Dis. 2020;14.

Improvement in symptoms

The greater benefit of UMEC/VI versus monotherapy was apparent within 2 days.12

Improvements-in-E-RS-score-with-UMEC/VI-versus-monotherapy from-Day-1-to-Day 7

The figure has been independently created by GSK from data first published in Kerwin EM, et al. Ther Adv Respir Dis. 2020;14 with permission.

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Improvement in lung function

UMEC/VI also demonstrated improvements in lung function at Week 24 versus monotherapy in both the ITT population3 and in maintenance-naive patients.13

Change-from-baseline-in-trough-FEV1-at-Week-24-in-the-ITT population

Figure adapted from Maltais F, et al. Respir Res. 2019;20:238. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/

Improvement in lung function

UMEC/VI also demonstrated improvements in lung function at Week 24 versus monotherapy in both the ITT population3 and in maintenance-naive patients.13

Change-from-baseline-in-trough-FEV1-at-Week-24-in-the maintenance-naive-subgroup

The figure has been independently created by GSK from data first published in Bjermer L, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:1939–1956.

Summary

gsk-ung-icon

Dual therapy with LAMA/LABAs has been shown to improve lung function, symptoms and quality of life versus monotherapy, without compromising safety.

EMAX-trial-icon

Patients treated with UMEC/VI experienced a significant improvement in COPD symptoms versus monotherapy, regardless of their baseline symptom severity. UMEC/VI also provided improvements in lung function versus monotherapy, in both the ITT and maintenance-naïve populations.

Abbreviations

AE, adverse events; ATS, American Thoracic Society; BID, twice daily; CAT, COPD Assessment Test; CI, confidence interval; CID, clinically important deterioration; COPD, chronic obstructive pulmonary disease; CrI, credible interval; E-RS:COPD, Evaluating Respiratory Symptoms:COPD; FEV1, forced expiratory volume in 1 second; FOR, formoterol fumarate; FVC, forced vital capacity; GLY, glycopyrronium; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IC, inspiratory capacity; ICS, inhaled corticosteroids; IND, indacaterol; ITT; intent-to-treat; LABA, long-acting B2-agonist; LAMA, long-acting muscarinic antagonist; LS, least squares, OLO, olodaterol; QD, once daily; RCT, randomised controlled trial; SAC, self-administered computerised, SAE, serious adverse events; SAL, salmeterol; SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnoea Index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol

References

  1. Nici L, et al. Am J Respir Crit Care Med. 2020;201(9):e56–e69
  2. GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2021. Available at: https://goldcopd.org/2021-gold-reports/ [accessed April 2021].
  3. Oba Y, et al. Thorax. 2016;71:15–25
  4. Maltais F, et al. Respir Res. 2019;20:238
  5. Maleki-Yazdi MR, et al. Adv Ther. 2017;33:2188─2199
  6. Buhl R, et al. Eur Respir J. 2015;45:969─979
  7. Bateman ED, et al. Eur Respir J. 2013;42;1484─1494
  8. Martinez FJ, et al. Chest. 2017;151:340–357
  9. Wedzicha JA, et al. Lancet Respir Med. 2013;1:199─209
  10. Calverley PMA, et al. Lancet Respir Med. 2018;6:337─344
  11. Vogelmeier CF, et al. Ther Adv Respir Dis. 2020;14
  12. Kerwin EM, et al. Ther Adv Respir Dis. 2020;14
  13. Bjermer L, et al. Am J Respir Crit Care Med. 2019;199:A3317

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NX-GBL-UCV-WCNT-210001 | Date of preparation: August 2022