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The number needed to treat (NNT) indicates the number of patients who need to be treated for one additional responder to be seen with one therapy compared with another in a defined time period. This analysis of the Early MAXimization of bronchodilation for improving chronic obstructive pulmonary disease (COPD) stability (EMAX) trial evaluated the NNT for benefit in symptomatic, inhaled corticosteroids (ICS)-free patients at low exacerbation risk treated with the longacting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) umeclidinium/vilanterol (UMEC/VI) versus UMEC (a LAMA), or salmeterol (SAL; a LABA) over 24 weeks. Methods: This double-blind, parallel-group trial randomized patients 1:1:1 to 24 weeks of UMEC/VI 62.5/25 mcg once daily (n=812), UMEC 62.5 mcg once daily (n=804), or SAL 50 mcg twice daily (n=809). NNT was calculated for each outcome from the proportion of patients experiencing a clinically relevant improvement or avoiding deterioration (responders) with UMEC/VI versus UMEC or SAL. Response was defined as: ≥1-point improvement in Transient Dyspnea Index (TDI) score; ≥2-point reduction from baseline in Evaluating Respiratory Symptoms (E-RS) total score; ≥4-point reduction from baseline in St George's Respiratory Questionnaire (SGRQ) total score; ≥2-point reduction from baseline in COPD Assessment Test (CAT) total score; avoiding a moderate/severe exacerbation; or avoiding a clinically important deterioration (CID) event (defined as one or more of: a ≥100 mL decrease in trough forced expiratory volume in 1 second [FEV 1 ], a ≥4-point reduction in SGRQ score, or a moderate/severe exacerbation). NNT was calculated post hoc for the proportion of patients achieving ≥100 mL increase in FEV 1 . Results: Across all outcomes over 24 weeks, fewer patients needed to be treated with UMEC/VI for one additional responder versus SAL (Figure). Aside from SGRQ and exacerbations, for which an NNT 95% confidence interval (CI) upper limit could not be determined, UMEC/VI also resulted in a lower NNT versus UMEC. Over 24 weeks, for the majority of endpoints, the NNT was lower for comparisons of UMEC/VI versus SAL than for comparisons of UMEC/VI versus UMEC. Of the seven outcomes analyzed, the NNT most in favor of UMEC/VI versus UMEC or SAL was observed for FEV 1 responder rate. Conclusion: These findings provide evidence of greater clinical benefit across a range of clinical outcomes over 24 weeks in symptomatic, ICS-free patients at low exacerbation risk with UMEC/VI compared with LAMA or LABA monotherapy. These data may facilitate physicians' choice of maintenance therapy. Funding: GlaxoSmithKline (201749; NCT03034915).

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Results from FULFIL have shown statistically significant improvements in lung function and health-related quality of life, and a reduction in exacerbation rates with once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100 µg/62.5 µg/25 µg administered using a single ELLIPTA® inhaler compared with twice-daily budesonide/formoterol (BUD/FOR) 400 µg/12 µg using the Turbuhaler® in patients with symptomatic COPD at risk of exacerbations. The safety profile of FF/UMEC/VI reflected that of the components (Lipson, et al. Am J Respir Crit Care Med. 2017). Herein we present post-hoc subgroup analyses of exacerbation rates by prior COPD medication class, disease severity and exacerbation history during FULFIL. In the intent-to-treat (ITT; 24 weeks) population, the mean annual exacerbation rate, FF/UMEC/VI versus BUD/FOR ratios and annual exacerbation rates reductions were calculated for subgroups: by prior COPD medication class, inhaled corticosteroid (ICS) +long acting beta agonists (LABA); BUD/FOR; ICS +LABA + long-acting muscarinic antagonists (LAMA); LAMA; tiotropium; LAMA +LABA; by disease severity, forced expiratory volume in 1 s (FEV1) <50% predicted, no moderate/severe exacerbation; FEV1 <50%,≥1 moderate/severe exacerbation; FEV1 ≥50–≤80%,≥2 moderate or ≥1 severe exacerbations; and by exacerbation history, 0/1 moderate exacerbations;≥2 moderate exacerbations;≥1 severe exacerbation. Up to Week 24 in the ITT population, FF/UMEC/VI versus BUD/FOR improved the mean annual exacerbation rate (range, 63%–24%) in all prior medication subgroups, except LAMA +LABA (annual exacerbation rate reduction, −44%) and improved mean annual exacerbation rates in all disease severity (range, 45%–27%) and exacerbation prior history (range, 57%–27%) subgroups (Table). Statistical significance of the FF/UMEC/VI:BUD/FOR ratio was observed for the subgroups: prior medication class ICS +LABA (0.37; 95% confidence interval [CI] 0.20–0.71; p=0.003) and ICS +LAMA + LABA (0.53; 95% CI 0.33–0.87; p=0.012); disease severity FEV1 <50% and≥1 moderate/severe exacerbation (0.55; 0.34–0.89; p=0.015); exacerbation history 0/1 prior moderate exacerbation (0.62; 0.44 0.87; p=0.005) and ≥1 prior severe exacerbation (0.43; 0.22 0.86; p=0.017) (Table). Improvements in mean annual exacerbation rates with once-daily FF/UMEC/VI compared with twice-daily BUD/FOR were observed in all patients regardless of disease severity or exacerbation history and all prior COPD medication class subgroups except for LAMA +LABA.FundingGSK (NCT02345161; CTT116853)Please refer to page A260 for declarations of interest in relation to abstract P272.Abstract P272 Table 1Mean annual exacerbation rates by subgroup (ITT population; up to Week 24) Subgroup FF/UMEC/VI 100/62.5/25 µg (n= 911) BUD/FOR 400/12 µg (n=899) Reduction in annual exacerbation rate n rate n rate % (95% CI) Prior medication ICS+LABA 266 0.10 258 0.27 63* (29–80) BUD+FOR 87 0.05 83 0.10 54 (−74–88) ICS+LABA+LAMA 256 0.28 254 0.53 47* (13–67) LAMA alone 79 0.12 79 0.23 49 (−42–81) TIO alo...

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