Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD

Int J Chron Obstruct Pulmon Dis. 2021 Mar 1:16:499-517. doi: 10.2147/COPD.S291967. eCollection 2021.

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens. International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations. Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD. Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use. We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence. Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes. Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality. These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA. Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons. Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making. We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes.

Keywords: ICS; LABA; LAMA; all-cause mortality; exacerbations; hospitalizations.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / adverse effects
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Bronchodilator Agents / adverse effects
  • Drug Therapy, Combination
  • Humans
  • Muscarinic Antagonists / adverse effects
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Muscarinic Antagonists

Grants and funding

Editorial support (in the form of writing assistance, collating author comments, assembling tables/figures, grammatical editing, fact checking, and referencing) was provided by Carol A. Richter, PhD, of Gardiner-Caldwell Communications (Macclesfield, UK) and Chrystelle Rasamison, at Fishawack Indicia Ltd. part of Fishawack Health, UK, and was funded by GlaxoSmithKline (GSK).