The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods

Figures & data

Table 1 Included studies

Authors	RCT design	F/U weeks	Agea	FEV1 %a	Pack-yearsa	Comparison	Primary outcome
Aaron et al^Citation4	Double-blind	52	67.7	41.8	50.3	TIO + FP (1,000 μg/d)/SAL (n=145) vs TIO (n=156)	Exacerbation of disease
Cazzola et al^Citation5	Double-blind	12	65.8	38.1	50.9	TIO + FP (1,000 μg/d)/SAL (n=29) vs TIO (n=26)	Change in predose FEV1
Welte et al^Citation10	Double-blind	12	62.5	37.9	37	TIO + BUD (640 μg/d)/FOR (n=329) vs TIO (n=331)	Change in predose FEV1
Hanania et al^Citation6	Double-blind	24	61.2	56.7	55.1	TIO + FP (500 μg/d)/SAL (n=173) vs TIO (n=169)	Change in predose FEV1
Jung et al^Citation8	Open-label	24	67.4	47.5	NR	TIO + FP (500 μg/d)/SAL (n=237) vs TIO (n=242)	Change in predose FEV1
Hoshino and Ohtawa^Citation7	Open-label	16	71.2	NR	57.7	TIO + FP (500 μg/d)/SAL (n=15) vs TIO (n=15)	Airway dimension
Maltais et al^Citation9	Double-blind	4	62.7	54.7	NR	TIO + FP (500 μg/d)/SAL (n=124) vs TIO (n=131)	Exercise endurance time

Note:

a Mean value.

Abbreviations: RCT, randomized controlled trial; TIO, tiotropium; FP, fluticasone propionate; SAL, salmeterol; BUD, budesonide; FOR, formoterol; NR, not recorded; F/U, follow-up; FEV₁, forced expiratory volume in the first second.

Figure 1 Flowchart for the selection of studies.

Abbreviations: COPD, chronic obstructive pulmonary disease; RCT, randomized controlled trial; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist.

Figure 2 Risk of bias summary and table.

Table 2 Summary of efficacy outcomes

Outcome variable	Number of studies	Total number of patients included		RR or MD (95% CrI)	Posterior probability	SD
		Triple therapy	TIO monotherapy
Deatha	3	705	725	1.46 (0.13–5.17)	P (RR <1) =0.47	1.72
Acute exacerbationa	4	870	888	0.80 (0.35–1.63)	P (RR <1) =0.84	0.37
Changes in FEV1 b	6	915	928	63.68 mL (45.29–82.73)	P (MD <0 mL) =1.0 P (MD >100 mL) =0.002	9.69
Changes in SGRQb	3	697	711	−3.11 points (−6.00 to −0.80)	P (MD <0) =0.99 P (MD <−4) =0.18	2.16

Notes:

a RR for binary outcomes,

b MD for continuous outcomes.

Abbreviations: FEV₁, forced expiratory volume in the first second; TIO, tiotropium; SGRQ, St George Respiratory Questionnaire; RR, relative risk; CrI, credible interval; MD, mean difference; SD, standard deviation (between studies).

Figure 3 The efficacy of triple therapy compared with tiotropium monotherapy.

Notes: (A) Death; (B) acute exacerbation; (C) changes in FEV₁; (D) changes in SGRQ.
Abbreviations: FEV₁, forced expiratory volume in the first second; TIO, tiotropium; SGRQ, St George Respiratory Questionnaire; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; SD, standard deviation; RR, relative risk; CrI, credible interval; MD, mean difference.

Table 3 Summary of adverse events

Outcome	Number of studies	Total number of patients included		RR (95% CrI)	Posterior probability	SD
		Triple therapy	TIO monotherapy
Total adverse events	5	800	813	1.12 (0.87–1.40)	P (RR >1) =0.84	0.14
Severe adverse events	6	1,031	1,051	0.62 (0.17–1.25)	P (RR <1) =0.93	0.29
Pneumonia	4	829	856	1.07 (0.05–4.28)	P (RR >1) =0.27	3.63
Oral candidiasis	3	647	656	3.63 (0.46–12.82)	P (RR >1) =0.88	4.53

Abbreviations: TIO, tiotropium; RR, relative risk; CrI, credible interval; SD, standard deviation (between studies).

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