Comparative effectiveness of triple versus dual inhaled therapy (ICS/LABA or LABA/LAMA) for chronic obstructive...

The optimal role of triple therapy (ICS/LAMA/LABA) versus dual therapy in COPD remains uncertain, particularly given the trade-off between modest efficacy gains and potential safety concerns. In particular, whether triple therapy provides additional benefit over dual regimens consisting of either ICS/LABA or LABA/LAMA remains an important clinical question. This study aimed to evaluate the comparative effectiveness and safety of triple versus dual inhaled therapies in COPD using a network meta-analysis.

A systematic search of PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases was conducted from inception to July 2023. Randomized controlled trials comparing triple inhaled therapy with either ICS/LABA or LABA/LAMA dual inhaled therapy in COPD were eligible. Outcomes included moderate-to-severe exacerbations, forced expiratory volume in one second (FEV₁), St. George's Respiratory Questionnaire (SGRQ), Transition Dyspnea Index (TDI), and pneumonia incidence. Data were synthesized using a frequentist random-effects NMA. Treatment hierarchies were estimated using surface under the cumulative ranking curve (SUCRA).

Seven RCTs (n = 9,968 participants) were included. Triple therapy did not consistently reduce exacerbation rates compared with dual therapy, while dual regimens such as FF/VI and BUD/FORM ranked favorably for exacerbation prevention (SUCRA 75.6% and 71.4%). Triple therapy and selected dual regimens improved lung function, though SUCRA rankings unexpectedly favored BUD/FORM. Improvements in SGRQ and TDI were modest and often below the minimal clinically important difference. Pneumonia risk tended to be higher with fluticasone-containing regimens, though differences did not reach statistical significance.

Triple therapy was associated with improvements in some outcomes, particularly lung function, but did not show consistent statistically significant superiority over dual therapy across all endpoints in this network meta-analysis. Given the small number of included trials and limited power for some comparisons, these findings should be interpreted cautiously and should not be taken as evidence of equivalence. Dual regimens remained effective options, while triple therapy may still be beneficial in selected high-risk patients. Personalized treatment based on exacerbation history, eosinophil count, and pneumonia risk remains essential.

Not applicable.