A32-18 An Indirect Comparison of Budesonide/ Glycopyrrolate/ Formoterol Fumarate Versus Fluticasone/ Umeclidinium/ Vilanterol in Adults With Uncontrolled Asthma From a US Perspective: A Systematic Review and Network Meta Analysis

Rationale Budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FOR 320/36/9.6 µg), delivered via Aerosphere inhaler, was evaluated in the KALOS and LOGOS trials which included a comparison with the marketed Symbicort® pressurized MDI in uncontrolled asthma patients with or without recent exacerbation history [NCT04609878, NCT04609904]. BUD/GLY/FOR demonstrated superiority to Symbicort® for improving lung function and in reducing severe exacerbations. In CAPTAIN, adding umeclidinium (UMEC) to fluticasone/vilanterol (FF/VI) improved lung function versus FF/VI alone but did not lead to a significant reduction in severe exacerbations. However, the comparative efficacy between approved single inhaler triple therapies (SITTs) remains unknown. Methods A systematic literature review identified randomized controlled trials of single-inhaler triple therapies (SITTs) in uncontrolled asthma. This network meta-analysis (NMA) compared the clinical efficacy budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FOR) with SITTs containing medium-dose inhaled corticosteroids (MD-ICS) including fluticasone/umeclidinium/vilanterol (FF/UMEC/VI), which is the only currently marketed SITT for asthma in the US. Analyses were conducted compared to pooled FF/UMEC/VI doses (100/62.5/25 and 200/62.5/25) and for FF/UMEC/VI 100/62.5/25 alone. Endpoints included trough FEV1 at 24 (±4) weeks and severe exacerbations at 52 weeks. A Bayesian framework was applied, and fixed-effect models were selected due to the limited number of studies per outcome. Results BUD/GLY/FOR demonstrated an 18% numerical reduction in severe exacerbations [RR, (95%CI): 0.82 (0.65,1.03)] and no significant difference in lung function [mean difference, (95% CI): -13.99 (-55.23, 27.55)] compared to pooled FF/UMEC/VI (100/62.5/25 & 200/62.5/25). BUD/GLY/FOR demonstrated statistically significant reduction of 28% in severe exacerbations versus FF/UMEC/VI (100/62.5/25) [RR, (95%CI): 0.72 (0.55,0.95)] and no significant difference in lung function [mean difference, (95% CI): -17.17 (-65.46, 31.16)]. Conclusions This study suggests that treatment with BUD/GLY/FOR leads to greater reduction in severe exacerbations compared with FF/UMEC/VI for uncontrolled asthma patients with or without recent exacerbation history and can inform clinical and treatment decision making.