Clinical Remission with FF/UMEC/VI Versus ICS/LABA in Uncontrolled Asthma: The PERFORM Pragmatic Randomized Controlled Trial

Prospective, randomized evidence for clinical remission, an ambitious treatment goal relevant for all patients with asthma, with single-inhaler triple therapy (SITT) in routine care is lacking. Significant improvement in lung function and asthma control with SITT versus inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) was demonstrated in PERFORM at week 24. PERFORM (GSK 219912/NCT06372496), a randomized, open-label, active-controlled, global pragmatic trial, evaluated the effectiveness and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus usual care ICS/LABA in adults (18–75 years) with uncontrolled, infrequently exacerbating asthma. Secondary outcomes related to clinical remission (no oral corticosteroid use, no severe exacerbations, optimized lung function [change from baseline (CFB) in forced expiratory volume in 1 second (FEV1) ≥ 100 mL], asthma control [Asthma Control Questionnaire total score < 1.50]) were assessed at week 52, following prespecified analysis plans. Alternative clinical remission definitions using stabilized lung function (CFB FEV1 ≥ 0 mL) and those within Japanese guidelines were also assessed. Clinical remission responder analyses are presented as multiplicity-adjusted odds ratios. Safety was assessed throughout. Overall, 1236 participants (mean age 48.9 years; 68.6% [n = 848/1236] female) were included (FF/UMEC/VI: N = 619/1236; ICS/LABA: N = 617/1236). Participants receiving FF/UMEC/VI had statistically significantly greater odds of achieving clinical remission (including optimized lung function) at week 52 versus usual care ICS/LABA (adjusted odds ratio [95% confidence interval] 2.13 [1.54, 2.94], P < 0.0001). Similar results were observed for alternative definitions. Week 52 safety profile aligned with previous studies. In a broad patient population with uncontrolled asthma, treatment with FF/UMEC/VI resulted in statistically significantly greater odds of achieving clinical remission versus usual care ICS/LABA in a setting reflecting routine practice, a secondary outcome of PERFORM. These findings were consistent irrespective of clinical remission definitions and provide evidence informing the use of FF/UMEC/VI in an underserved group of symptomatic patients with infrequent exacerbations and minimal lung function impairment. GSK 219912/NCT06372496.