Effect of once-daily ICS/LAMA/LABA triple therapy versus ICS/LABA on respiratory symptoms (E-RS: Asthma): Analysis of the phase IIIA CAPTAIN trial

Background Addition of the long-acting muscarinic antagonist umeclidinium (UMEC) to the inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination fluticasone furoate/vilanterol (FF/VI) improved lung function in adults with uncontrolled moderate to severe asthma in the CAPTAIN (Clinical study of Asthma Patients receiving Triple therapy through A single INhaler) study; however, the impact on symptoms requires further investigation.Objective We sought to evaluate the effect of adding UMEC to FF/VI on asthma symptoms.Methods The CAPTAIN study was a phase IIIA, randomized, controlled, 24- to 52-week study of patients with uncontrolled moderate to severe asthma despite ICS/LABA receiving once-daily single-inhaler FF/VI (100/25 or 200/25 μg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, or 200/62.5/25 μg). Here, we compare the effect of pooled FF/UMEC 62.5/VI (100/62.5/25 and 200/62.5/25 μg) versus FF/VI (100/25 and 200/25 μg) on symptom control using prespecified analyses of change from baseline in Evaluating Respiratory Symptoms in Asthma (E-RS: Asthma) total and domain scores, and proportion of patients meeting an E-RS: Asthma total score responder threshold. We also performed post hoc analyses assessing the impact of baseline type 2 inflammation status on treatment response.Results Least-squares mean (95% CI) reductions from baseline in E-RS: Asthma total score exceeded the minimum clinically important difference (-2.0 units) and were numerically greater with FF/UMEC 62.5/VI (-2.89 [-3.15 to -2.64]; n = 814) versus FF/VI (-2.47 [-2.73 to -2.22]; n = 813). The proportion of responders (45% [n = 360] vs 41% [n = 327]) and odds of response (odds ratio, 1.18 [95% CI, 0.96 to 1.45]) were numerically greater with FF/UMEC 62.5/VI versus FF/VI. Similar trends were observed irrespective of type 2 status.Conclusions Patients with symptomatic asthma may benefit from optimized treatment interventions, such as adding a long-acting muscarinic antagonist to ICS/LABA.