Placing Novel, Fixed-Dose Dual Bronchodilators within the nice Guidelines for Chronic Obstructive Pulmonary Disease -Reflections on the Past, Present and Future

The current National Institute for Health and Care Excellence (NICE) chronic obstructive pulmonary disease (COPD) guidelines were updated in 2010, reflecting clinical evidence available at that time. Since the guidelines were written, a growing body of evidence has demonstrated enhanced Bronchodilation with LABA/LAMA in fixed-dose combinations (FDCs) versus single component agents (the standard of care) in moderate to severe COPD. Studies to date indicate that the indacaterol/glycopyrronium (QVA149) and umeclinidium/vilanterol (UMEC/VI) can optimize Bronchodilation and may lead to improvements in patient-reported outcomes beyond lung function. The evidence for LABA/LAMA FDC, in particular glycopyrronium/indacaterol, and also umeclidinium/vilanterol, supported by meta-analysis, shows that dual Bronchodilation provides superior efficacy compared with LAMA monotherapy (glycopyrronium or tiotropium), and suggests the appropriateness of progression to LABA/LAMA combinations after LAMA mono therapy rather than escalation to LABA/ICS in patients with persistent breathlessness. The debate regarding the benefits and risks of LABA/ICS is on-going, with data now more firmly showing an association with inhaled ICS use and pneumonia. In patients with moderate or severe airflow obstruction and no history of exacerbations in the past year, randomised data showed that glycopyrronium/indacaterol was superior to LABA/ICS in improving lung function and breathlessness score. How to quantify the benefits of LABA/LAMA FDC over Mono therapy will be an ongoing debate, and consideration of other parameters such as a responder analysis of the proportion of patients that did achieve a threshold, may be better suited to establish clinically relevant differences between active agents and placebo. This review highlights the need to consider revisions to the current NICE COPD guidelines to reflect the recently published evidence demonstrating a role for LABA/LAMA FDC in the treatment of moderate to severe COPD