Comparing major COPD triple therapy trials using a structured multi-criteria decision analysis: A deep dive into patient populations and outcomes

Background: Triple inhaled therapy (ICS/LABA/LAMA) is widely recommended for managing COPD in patients with persistent symptoms or frequent exacerbations. However, variability in trial designs, populations, and pharmacologic formulations complicates direct comparison between regimens. Objective: To evaluate the comparative performance of three triple therapies, FF/VI/UMEC, BUD/FOR/GLY, and BDP/FOR/GLY, using a multidimensional comparative decision analysis (MCDA) across key clinical domains. Methods: Data from pivotal trials (IMPACT, FULFIL, TRINITY, TRIBUTE, TRILOGY, ETHOS, and KRONOS) were synthesized using an MCDA framework encompassing lung function, symptom control, and exacerbations. Mortality, safety, and device usability were also assessed. Analyses considered variations in enrolled populations, prior ICS use, and inhaler characteristics. Results: FF/VI/UMEC showed consistent efficacy across multiple domains and populations, particularly in patients at high risk of exacerbations. BUD/FOR/GLY was associated with reductions in exacerbations and mortality, particularly in patients previously treated with LABA/LAMA. BDP/FOR/GLY may be suitable for ICS-maintained patients. Trials like FULFIL and KRONOS showed symptom and lung function gains even in non-exacerbators, although ICS use in this group always warrants caution due to pneumonia risk. Limitations: Findings are based on indirect comparisons across heterogeneous trials. Relative changes from dual therapy comparators were evaluated, and pharmacological and device-related differences between each triple therapy and the comparators may have influenced outcomes. Conclusions: Among the therapies evaluated, FF/VI/UMEC achieved the highest composite MCDA score. However, optimal COPD management requires personalized treatment to be prescribed based on factors such as exacerbation history, previous ICS use, inhaler preference and adherence. This may involve evaluating the use of an alternative triple therapy and emphasizes the importance of aligning the choice of triple therapy with the individual's clinical profile and treatment goals.