O4.2.3 Fixed vs open triple therapy

More data are becoming available on different drug combinations and regimens, including open triple therapy (multiple inhalers collectively containing ICS, LAMA, and LABA) and fixed triple therapy (a fixed-dose single triple therapy inhaler containing ICS/LABA/LAMA).

The TRINITY study evaluated the fixed triple therapy (extra-fine beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide; n=1078) against open triple therapy (tiotropium with combination beclomethasone dipropionate and formoterol fumarate; n=538) and tiotropium alone (n=1075 control) (Vestbo 2017) [evidence level II]. The adjusted mean changes from baseline in pre-dose FEV₁ at week 52 of TRINITY were 0·082 L (95% CI 0·065 to 0·100) for fixed triple, 0·021 L (0·003 to 0·039) for tiotropium and 0·085 L (0·061 to 0·110) for open triple (Vestbo 2017) [evidence level II]. Moderate to severe COPD exacerbations were 0·46 (0·41–0·51) per patient per year for fixed triple, 0·57 (0·52–0·63) for tiotropium, and 0·45 (0·39–0·52) for open triple, meaning fixed triple was superior to tiotropium (adjusted RR 0·80, 95% CI 0·69 to 0·92; p=0·0025). The time to first severe exacerbation was prolonged with fixed triple compared with tiotropium (HR 0·70, 95% CI 0·52 to 0·95; p=0·0208) and was similar for fixed triple and open triple (1·05 [0·70–1·56]; p=0·82) (Vestbo 2017) [evidence level II]. The incidence of adverse events (55 to 58%), serious adverse events (13 to 15%) and pneumonia (1 to 2%) were similar across the fixed triple, open triple, and control groups (Vestbo 2017) [evidence level II]. A meta-analysis of 2 trials (Bremner 2018, Vestbo 2017) directly comparing fixed triple therapy with separate triple therapy found no statistically significant associations for all the outcomes, including exacerbations of COPD, lung function, adverse events and HRQoL (Zheng 2018).