Table 3.

Effect of LABA/LAMA versus LAMA or LABA/ICS on secondary COPD outcomes

Outcome measure	Studies included	No of patients		Estimate	Effect (95% CI)	I2, % (P-value)
		LABA/LAMA	Comparator
TDI focal score from baseline to
LABA/LAMA versus LAMA
Week 12	25, 28–30, 33	2,059	2,471	Mean difference	0.50 (0.32, 0.68)	0 (<0.0001)
Week 24	7, 25, 29, 30, 32	2,653	3,064		0.29 (0.12, 0.46)	0 (0.0006)
Total assessed for MCIDa	7, 15, 25, 28–31, 33	2,444	2,865	Relative risk	1.12 (1.06, 1.18)	18 (0.0002)
Total with MCID		1,500	1,604	NNTB	19 (12, 36)
LABA/LAMA versus LABA/ICS
Week 12	34, 35, 37, 38	1,581	1,567	Mean difference	0.20 (−0.03, 0.42)	3 (0.09)
Week 26	34, 35	579	575		0.33 (−0.28, 0.95)	0 (0.29)
Health status (SGRQ) from baseline to
LABA/LAMA versus LAMA
Week 12	7, 25, 26, 28–31, 33	4,101	5,189	Mean difference	−1.84 (−2.31, –1.37)	0 (<0.0001)
Week 24	7, 25, 26, 29, 31, 32	3,679	4,750		−1.34 (−1.94, −0.75)	0 (<0.0001)
Week 52	7, 26	1,987	2,539		−1.21 (−2.64, 0.21)	58 (0.09)
Total assessed for MCIDb	7, 15, 25, 26, 28–31, 33	4,450	5,385	Relative risk	1.14 (1.09, 1.20)	39 (<0.0001)
Total with MCID		2,493	2,668	NNTB	16 (12, 22)
LABA/LAMA versus LABA/ICS
Week 12	34–38	3,122	3,099	Mean difference	−0.43 (−1.28, 0.42)	48 (0.32)
Week 26	34–36	2,160	2,143		−1.131 (−1.78, −0.48)	0 (0.0006)
Rescue medication use at EOT versus baseline
LABA/LAMA versus LAMA
Treatment period range (12–64 weeks)	25, 26, 28–31	2,769	3,744	Mean difference	−0.58 (−0.70, −0.45)	0 (<0.0001)
LABA/LAMA versus LABA/ICS
Treatment period range (12–26 weeks)	34–38	3,275	3,289	Mean difference	−0.18 (−0.28, −0.07)	0 (0.001)

Notes:

^aMCID of TDI: ≥1 unit.

^bMCID of SGRQL ≥4 units.

Abbreviations: CI, confidence interval; EOT, end of treatment; MCID, minimum clinically important difference; NNTB, number needed to treat for benefit; SGRQ, St George’s Respiratory Questionnaire; TDI, transitional dyspnea index; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist.