Single inhaler triple therapy (ICS/LAMA/LABA) in patients with advanced COPD: German responder results for patient reported symptom E-RS and subscale analyses from the FULFIL trial

Rationale:

FULFIL was a 24 week phase III, randomized, double-blind, double-dummy trial comparing FF/UMEC/VI (od 100 µg/62.5 µg/25 µg) via a single ELLIPTA inhaler with BUD/FOR (bid 400 µg/12 µg) via TURBUHALER in symptomatic COPD patients at risk of exacerbations. This study demonstrated statistically significant improvements in lung function and SGRQ with FF/UMEC/VI versus BUD/FOR (Lipson, et al. AJRCCM 2017). Patient reported symptom severity was assessed using the Evaluating Respiratory Symptoms in COPD [E-RS:COPD] tool.

Methods:

E-RS:COPD was completed each evening by participants in an e-diary and analysed up to week 24 (W24) and week 52 (W52). Post-hoc responder analyses were based on a 2-weekly (W24) and 4-weekly (W52) mean score, using the distribution based thresholds of -3.35 for the total E-RS:COPD score, -1.85 for breathlessness, -1.15 for cough and sputum and -1.05 for chest symptoms.

Results:

1810 participants were included in the ITT population (FF/UMEC/VI, n = 911; BUD/FOR, n = 899) up to week 24. The first 430 participants completed up to 52 weeks (EXT). Over both time periods, FF/UMEC/VI produced greater reductions from baseline in mean E-RS:COPD score compared with BUD/FOR leading to statistically significant differences for proportion of responders (ITT: p < 0.001 W23 – 24; EXT: p = 0.016 W49 – 52). The ratio between treatments of odds of response versus non-response was statistically significant in favour of FF/UMEC/VI (odds ratios [OR] of 1.51; 95% CI 1.22, 1.87 W23 – 24 and OR 1.74; 95% CI 1.11, 2.74 W49 – 52). Response rates for breathlessness, cough and sputum, and chest symptoms were significantly improved during weeks 23 – 24 (p < 0.001 to 0.028) and weeks 49 – 52 (p < 0.001 to p = 0.645).

Comparison with a 4-weekly average using pre-specified response thresholds of -2.00 for the total E-RS:COPD score, -1.00 for breathlessness, -0.70 for cough and sputum and chest symptoms, showed similar statistically significant results in favour of FF/UMEC/VI versus BUD/FOR.

Conclusions:

FF/UMEC/VI was associated with greater improvements from baseline in E-RS:COPD and subscale scores compared with BUD/FOR. Irrespective of different responder definitions, the evaluation of the E-RS:COPD consistently demonstrated statistically significant improvements in favour of FF/UMEC/VI versus BUD/FOR.