Single inhaler triple therapy in patients with advanced COPD (FULFIL): exacerbation/pneumonia composite outcomes

Abstract

Background: FULFIL reported statistically significant improvements in lung function and health status with once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100μg/62.5μg/25μg via the ELLIPTA® inhaler vs twice-daily budesonide/formoterol (BUD/FOR) 400μg/12μg via the Turbuhaler® in patients with advanced COPD (Lomas et al. ERJ 2016;48:PA4629). Given the clinical overlap of exacerbations and pneumonia, we analysed composites of these outcomes to assess the overall benefit/risk of FF/UMEC/VI compared with BUD/FOR. Methods: We performed post-hoc analyses in the ITT (24 weeks; FF/UMEC/VI, n=911; BUD/FOR, n=899) and extension (EXT; 52 weeks; FF/UMEC/VI, n=210; BUD/FOR, n=220) populations. There were two composite outcomes: time-to-first investigator-reported moderate (required antibiotics or oral/systemic corticosteroids)/severe (required hospitalisation) exacerbation or pneumonia event (investigator reported by a prespecified list of preferred terms); and time-to-first severe exacerbation/hospitalised pneumonia event. Analyses were based on a proportional hazards model. Results: For moderate/severe exacerbation or pneumonia, FF/UMEC/VI had a statistically significant reduction in risk vs BUD/FOR of 25% (ITT; 109 [12%] vs 130 [14%]; p=0.027) and 44% (EXT; 37 [18%] vs 63 [29%]; p=0.006). For severe exacerbation/hospitalised pneumonia, FF/UMEC/VI had a lower risk vs BUD/FOR of 17% (ITT; 22 [2%] vs 24 [3%]; p=0.541) and 65% (EXT; 8 [4%] vs 23 [10%]; p=0.010). Conclusion: The results of these exacerbation/pneumonia composite outcomes support a favourable benefit/risk profile of once-daily FF/UMEC/VI compared with BUD/FOR in patients with COPD. Funding: GSK (CTT116853)