Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: an overview of systematic reviews.

BACKGROUND: Some systematic reviews (SRs) on triple therapy (consisting of long-acting β2 -agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for chronic obstructive pulmonary disease (COPD) have reported conflicting results. As the number of syntheses increases, the task of identifying and interpreting evidence becomes increasingly complex and demanding.

OBJECTIVES: To provide a comprehensive overview of the efficacy and safety of triple therapy for COPD.

DESIGN: Overview of SRs.

METHODS: Two independent reviewers conducted comprehensive searches in PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant SRs that compared triple therapy with any non-triple therapy for COPD, from the inception of these databases until 1 June 2023. The AMSTAR 2 and GRADE tools were utilized to assess the quality of the included studies and the evidence for each outcome.

RESULTS: Eighteen SRs encompassing 30 original studies and involving 47,340 participants were analyzed. The overall AMSTAR 2 rating revealed that 3 SRs were of low quality, 13 SRs were of critically low quality, and 2 SRs were of high quality. No high-certainty evidence revealed a significant advantage of triple therapy in improving lung function or reducing acute exacerbations. However, all evidence, including one high certainty, supported the benefits of improving quality of life. Regarding all-cause mortality, no significant difference was found when compared to LAMA or ICS/LABA; however, high-certainty evidence confirmed its effectiveness when compared with LABA/LAMA. Notably, high-certainty evidence indicated that triple therapy was associated with a significant increase in the risk of pneumonia compared to LABA/LAMA.

CONCLUSION: Triple therapy demonstrated notable benefits in improving lung function, reducing exacerbations, improving quality of life, and reducing all-cause mortality. However, it is important to note that it may also significantly increase the risk of pneumonia.

TRIAL REGISTRATION: This overview protocol was prospectively registered with PROSPERO (No. CRD42023431548).