Three drugs in one inhaler for COPD :where are we going with triple therapy

Dr Brian Lipworth

Scottish Centre for Respiratory Research University of Dundee

Ninewells Hospital and Medical School

University of Dundee ,DD1 9SY

Summary

Single inhaler triple therapy comprising ICS/LABA/LAMA for COPD have been developed to improve patient adherence . The ICS moiety reduces eosinophilic inflammation while the LABA/LAMA improves airway calibre .Current guidelines advocate triple therapy for frequently exacerbating patients in GOLD group D.Evidence suggests that single inhaler triple is superior to either ICS/LABA or LABA/LAMA in reducing exacerbations while having a much smaller effect on lung function and quality of life . Patients with an eosinopihilic COPD phenotype fare better in terms of exacerbation reduction with triple therapy . The ICS moiety is also related to an increased pneumonia risk especially for fluticasone furoate  compared to either budesonide or beclometasone dipropionate , which in turn is related to their relative lipophilicity and associated lung retention in the presence of impaired mucociliary clearance and altered lung microbiome . This is in turn may determine which triple inhaler is optimal in terms of the overall benefit-risk equation for treating COPD . Other factors such as device preference (DPI vs pDMI) , particle size and  dosing regimen (od vs bid) will also influence individual prescribing . Triples currently available or in development include fluticasone furoate /vilanaterol/umeclidinium (od DPI) , becometasone dipripionate/formoterol/glycopyrronium (bid extra fine solution pMDI) and budesonide/formoterol/glycopyrronium  (bid  co-suspension pMDI) .