Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide and is expected to become the third leading cause of death by 2030.1 The annual financial burden of lung disease in Europe is €141 billion, of which COPD accounts for almost half.2 Current treatment aims are to improve lung function, mitigate symptoms and to reduce the frequency and severity of exacerbations.3 Unsurprisingly, COPD formed the focus of a number of industry presentations at the 27th European Respiratory Society Congress, which was held on 9–13 September 2017 in Milan, Italy.
GlaxoSmithKline (GSK) presented efficacy and safety data from METREX and METREO, two phase III studies of mepolizumab, an investigational add-on treatment for patients with eosinophilic COPD. The study populations had a history of frequent exacerbations, despite receiving optimal standard of care treatments, and most were categorised as stage D, the most advanced disease, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Overall, COPD patients with blood eosinophil counts of >150 cells/µL at study entry or >300 cells/µL within the past year showed a consistent 18–20% reduction in the primary endpoint of annual rate of moderate and severe exacerbations when treated with add-on 100 mg mepolizumab. There was no increased benefit from a higher (300 mg) dose of mepolizumab investigated in the dose-ranging METREO study. In the METREX study, patients with blood eosinophil counts of less than 150 cells/µL at the start of the study (i.e. patients with non-eosinophilic COPD) did not benefit from mepolizumab. Mepolizumab was found to have the greatest impact on the annual rate of moderate or severe exacerbations among patients with higher blood eosinophil counts at screening.4 These data highlight the benefits of a personalised approach to the treatment of COPD with mepolizumab, using blood eosinophils as a biomarker.
In addition, GSK presented new data from the FULFIL (lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) study, which is comparing the effects of the once-daily investigational closed triple combination therapy fluticasone furoate/umeclidinium/vilanterol with twice daily budesonide/formoterol (Symbicort Turbohaler®) in patients with advanced COPD. The study has demonstrated clinically meaningful and statistically statistical benefits in terms of preventing clinically important deterioration (CID), a composite measure of worsening COPD.5
AstraZeneca presented results from INCONTROL 1, a first-of-its-kind post-hoc analysis of a large pooled data set of phase III COPD studies.6 This analysis identified patient characteristics that may affect the treatment response to budesonide/formoterol versus formoterol alone, and also investigated the relationship between blood eosinophil levels, risk of exacerbation and treatment selection in COPD. In COPD patients with a peripheral blood eosinophil level of 0.1 x109 cells/L or greater and who had experienced one or more exacerbations in the previous year, maintenance treatment with budesonide/formoterol 160/4.5 μg gave clinically meaningful reductions in exacerbations compared with formoterol 4.5 μg alone.
Further revisions to the GOLD international consensus guidelines7 were a major talking point at the meeting. A Novartis-sponsored symposium discussed the changes made to the severity classification and recommendations, in particular the incorporation of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) as the treatment of choice for patients with grade B, C, and even many with grade D. The reduced indications for inhaled corticosteroids (ICS) sparked considerable debate. This change was welcomed by Novartis, whose respiratory portfolio does not include either a LABA/ICS fixed-dose combination (FDC) or triple therapy for COPD. However, the news was less well received by other manufacturers. Cheisi presented data from a post-hoc analysis of their large TRILOGY (single-inhaler triple therapy versus inhaled corticosteroid plus long-acting beta-agonist therapy for COPD) and TRINITY (single-inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for COPD) clinical trials on their triple combination to align with the new recommendations. The reduced size of the patient population classified as grade D decreased the statistical significance of some of the results, but their formoterol/glycopyrronium/beclometasone triple therapy still showed a statistically significant decrease in exacerbations compared with either LAMA or LABA/ICS treatment.8
As a result of these findings and the data from GSK’s FULFIL study detailed above, many experts continue to recommend the use of ICS for patients with COPD whose disease remains unstable on dual therapy. In data released after the ERS meeting, GlaxoSmithKline announced positive results from their IMPACT (InforMing the PAthway of COPD Treatment) study, which compared a triple therapy (fluticasone furoate/umeclidinium/vilanterol) to a LABA/LAMA FDC (fluticasone furoate/vilanterol). The triple therapy showed a 15% reduction in the annual rate of on-treatment moderate/severe exacerbations compared with the LABA/LAMA FDC.9 This debate is likely to continue.
Teva presented data from a real-world evidence study showing that of 1,091 patients with respiratory disease (including 348 with COPD) who were using the DuoResp Spiromax® inhaler (budesonide/formoterol), 385 matched controls (132 with COPD) who switched to the Symbicort Turbohaler® (budesonide/formoterol) had non-inferiority in terms of disease control.3 The DuoResp Spiromax® aims to reduce common errors in inhaler technique for patients with asthma and COPD by delivering medication via a breath-activated, multi-dose dry powder inhaler (MDPI).
Nuvaria, a manufacturer of medical devices to treat obstructive lung diseases, presented one-year data from the AIRFLOW-1 clinical trial, which is evaluating the safety and efficacy of targeted lung denervation (TLD), a bronchoscopic procedure developed to relieve obstructive airway disease by disrupting overactive parasympathetic nerves to promote airway dilatation. These data suggest that TLD is feasible, safe, and provides a sustained treatment effect.10
Controversy persists over the merits of triple therapy versus LABA/LAMA FDCs. However, the ERS meeting showcased some exciting new developments in COPD therapy, including the importance of personalised therapy, new inhaler technology and novel approaches to COPD therapy.
1. WHO, Chronic obstructive pulmonary disease (COPD), Available at: www.who.int/respiratory/copd/en/ (accessed 4 October 2017).
2. EFA, European Federation of Allergy and Airways Diseases Patients’ Associations (EFA), COPD explained, Available at: www.efanet.org/get-advice/copd(accessed 4 October 2017).
3. Roche N, Benhaddi H, van der Tol M, et al., Real-life evaluation of budesonide/formoterol (DuoResp Spiromax®) for the management of asthma and COPD in the UK, Presented at: European Respiratory Society (ERS) International Congress, Milan, Italy, 9–13 September 2017, Abstract # PA937.
4. Pavord ID, Chanez P, Criner GJ, et al., Mepolizumab for eosinophilic chronic obstructive pulmonary disease, N Engl J Med, 2017,377:1613–29.
5. Naya I, Barnacle H, Birk R, et al., Clinically important deterioration in advanced COPD patients using single inhaler triple therapy: results from the FULFIL study, Presented at: European Respiratory Society (ERS) International Congress, Milan, Italy, 9–13 September 2017, Abstract # PA3248.
6. Bafadhel M, Peterson S, De Bias M, et al., Modelling peripheral blood eosinophils to identify response to budesonide in COPD: a post-hoc analysis, Presented at: European Respiratory Society (ERS) International Congress, Milan, Italy, 9–13 September 2017, Abstract # PA394.
7. Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD diagnosis, management and prevention, Available at: www.guidelines.co.uk/respiratory/copd-diagnosis-management-and-prevention/252878.article (accessed 4 October 2017).
8. Scuri M, Singh D, Fabbri L, et al., Late breaking abstract: Extrafine triple therapy reduces exacerbations in GOLD B COPD patients: post-hoc analysis of TRILOGY and TRINITY, Presented at: European Respiratory Society (ERS) International Congress, Milan, Italy, 9–13 September 2017, Abstract # OA2898.
9. GSK, GSK and Innoviva report positive headline results from IMPACT study showing single inhaler triple therapy Trelegy Ellipta reduced COPD exacerbations, Available at: www.gsk.com/en-gb/media/press-releases/gsk-and-innoviva-report-positive-headline-results-from-impact-study-showing-single-inhaler-triple-therapy-trelegy-ellipta-reduced-copd-exacerbations/ (accessed 4 October 2017).
10. Slebos D-J, Targeted lung denervation (TLD) in COPD: new data AIRFLOW-1 trial, Presented at: European Respiratory Society (ERS) International Congress, Milan, Italy, 9–13 September 2017, Abstract # 4851.