The 28th European Respiratory Society (ERS) International Congress was held in Paris, France on 15–19 September, 2018. The congress acts as a platform to share the latest research advances in respiratory medicine, and industry representatives presented data from numerous clinical trials. Unsurprisingly, chronic obstructive pulmonary disease (COPD), which continues to be a leading cause of death worldwide,1 was the focus of many of these presentations.
The benefits of triple therapy for COPD with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), remain uncertain. GlaxoSmithKline presented new analyses of data from the IMPACT study,2 a phase III clinical trial comparing the triple therapy fluticasone furoate (FF)/umeclidinium (UMEC)/ vilanterol (VI) (Trelegy Ellipta®) with two dual therapies: UMEC/VI (Anoro Ellipta®) and FF/VI (Relvar/Breo Ellipta®) in more than 10,000 patients with a history of at least one moderate/severe exacerbation in the previous year. A comparison of FF/UMEC/VI and UMEC/VI showed a significant reduction in the annual rate of moderate/severe exacerbations for the triple therapy (rate reduction 15%, p<0.001). Reductions were seen regardless of eosinophil levels.2
AstraZeneca presented data from the KRONOS trial, a 24-week study evaluating the triple fixed-dose combination budesonide/glycopyrronium/formoterol (BGF) metered dose inhaler (MDI) via co-suspension delivery technology in patients with moderate to very severe COPD. The use of BGF MDI improved lung function compared with dual therapies, with significant reductions in exacerbation rates compared with glycopyrronium/formoterol (GFF).3 Among AstraZeneca’s other presentations on COPD was data from a phase IIa study of AZD8871, a novel dual-acting bronchodilator in COPD patients. The inhaled therapy had a positive, dose-dependent effect on forced expiratory volume compared with placebo.4
Extrafine inhaled corticosteroid (ICS)-containing medications are known to lower the risk of COPD exacerbations but their efficacy in lowering mortality remains a topic of controversy. Chiesi presented a stratified safety pooled analysis of fatal adverse events comparing extrafine ICS-containing combinations versus ICS-free treatments. No differences were seen between treatments for respiratory fatal events. However, for non-respiratory fatal events, time to death was delayed for extrafine ICS-containing treatments versus ICS-free treatments.7
While MDIs and dry powder inhalers are recommended for long-term treatment in the vast majority of patients, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends nebulizers for specific patient populations, such as patients with very low inspiratory flow rates, in whom nebulizer treatment may provide more benefits than dry powder inhalers or MDIs.5 Theravance Biopharma, Inc. and Mylan N.V. presented data from a phase II study evaluating revefanacin (YupelriTM), an investigational LAMA currently under review by the US Food and Drug Administration (FDA) for the treatment of COPD. Revefanacin reduced the rate of COPD exacerbations by 15–18% compared with placebo. If approved, revefanacin will be the first once-daily, long-acting nebulized bronchodilator for the treatment of COPD.6
Acute exacerbations are a major contributor to the morbidity, costs and mortality associated with COPD. Among the therapeutic options for the treatment of acute exacerbations are antibiotics. Results of the Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM)-funded Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalisation (BACE) showed that the macrolide antibiotic azithromycin may significantly reduce treatment failure during the period of highest risk in COPD requiring hospitalisation. These benefits are lost, however, 6 months after discontinuing azithromycin.8 The long-term use of azithromycin has been shown effective in preventing exacerbations; however, inherent risks have been considered to exceed the benefits. This study has demonstrated that reducing the dose and duration of azithromycin treatment and restricting it to acute periods of high risk for treatment failure improves the benefit-risk profile, potentially providing a new treatment strategy for acute exacerbations.
In addition to pharmacological therapies, surgical interventions for COPD are also the focus of considerable research. Nuvaira Inc. presented the first results from the AIRFLOW II clinical trial, which is investigating the use of targeted lung denervation (TLD) in COPD.9 TLD is a medical procedure that targets the whole lung by bronchoscopically disrupting parasympathetic nerves, promoting airway dilation. A total of 82 COPD patients were randomised to either sham treatment (n=41) or active treatment with TLD (n=41). Results of the study showed that between 3–6.5 months, 32% of patients randomised to TLD plus tiotropium experienced respiratory adverse events compared with 71% of those receiving sham procedures (p=0.0008). While there was not a significant difference in all COPD exacerbations between the two arms in the first year of study, severe exacerbations requiring hospitalisation were reduced in the TLD arm (p=0.039), suggesting the treatment may have cost-effectiveness benefits. Serious adverse events occurred in 17 TLD patients versus 16 sham patients, respiratory events occurred in 6 TLD versus 15 sham, and gastrointestinal events occurred in 6 TLD patients versus 2 sham.9 This approach may be useful following first-line use of pharmaceutical treatments in COPD patients with uncontrolled or progressive disease.
The management of chronic conditions such as COPD requires complex planning and multidisciplinary teams. At ERS 2018, Philips unveiled its latest connected care product, Trilogy Evo, a portable life support ventilator platform designed to provide consistent therapy and monitoring as patients change care environments and when their condition changes.10
In summary, as our understanding of COPD evolves, so does the range of treatment and management options. Although we are a long way from developing a cure for COPD, these presentations have highlighted significant advances in COPD therapy.
1. World Health Organisation (WHO). Chronic obstructive pulmonary disease (COPD). Available at: www.who.int/respiratory/copd/en/ (accessed 3 October 2018).
2. Lipson DA, Barnhart F, Breley N, et al. Single inhaler triple-therapy (ICS/LAMA/LABA) versus dual-therapy (ICS/LABA or LAMA/LABA) in patients with COPD at risk of exacerbations: efficacy and safety results of the phase III IMPACT trial. Am J Respir Crit Care Med. 2018;197:A1014.
3. Ferguson GT, Rabe KT, Martinez FJ, et al. KRONOS: 24-week study of triple fixed-dose combination budesonide/glycopyrronium/formoterol (BGF) MDI via co-suspension delivery technology vs glycopyrronium/formoterol (GFF) MDI, budesonide/formoterol (BFF) MDI and BFF inhalation powder in COPD. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA1661.
4. Psallidas I, Singh D, Astbury C, et al. A phase 2a randomized, double-blind, placebo-controlled trial of AZD8871, a novel dual-acting bronchodilator in COPD patients. Am J Respir Crit Care Med. 2018;197:A7708.
5. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 2018 report. Available at: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf (accessed 3 October 2018).
6. Donohue JF, Sethi S, Barnes CN, et al. COPD exacerbations in the phase 3 revefenacin clinical trial program. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA1655.
7. Scuri M, Fabbri LM, Singh D, et al. Reduction in fatal events with ICS-containing medications: results of safety pooled analysis from the TRILOGY, TRINITY and TRIBUTE studies. Am J Respir Crit Care Med. 2018:197:A7725.
8. Vermeersch K, Gabravska M, Aumann J, et al. Azithromycin for acute COPD exacerbations requiring hospitalization – the BACE trial results. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA1654.
9. Slebos D-J, Shah P, Herth F, et al. A double-blind, randomized, sham-controlled study of Targeted Lung Denervation in patients with moderate to severe COPD. Presented at the 28th European Respiratory Society International Congress, 15–19 September, 2018, Paris, France. Abstract OA4929.
10. Philips. Philips unveils Trilogy Evo and growing portfolio of connected solutions at ERS 2018. Available at: https://www.philips.com/a-w/about/news/archive/standard/news/press/2018/20180914-philips-unveils-trilogy-evo-and-growing-portfolio-of-connected-solutions-at-ers-2018.html (accessed 3 October 2018).