Table 3. Summary of Findings and Strength of Evidence for LAMA as Add-on Therapy to Inhaled Corticosteroids (ICS) and LABA vs ICS and LABA (Control).

Outcome	Included Studies	ICS and LABA + LAMA		Control		Resultsa		Strength of Evidenced
		No. of Participants	Outcome Datab	No. of Participants	Outcome Dataa	Absolute Risk Difference (95% CI)c	Effect Size (95% CI)
Exacerbations
Requiring systemic corticosteroids	18,22	710	125	589	150	−0.5 (−8.1 to 7.0)	RR, 0.84 (0.57 to 1.22)	Moderate
Requiring hospitalizationc	Trial 118	237	8	222	10	−1.1 (−5.1 to 2.6)	RR, 0.75 (0.30 to 1.86)	Moderate
	Trial 218	216	8	232	10	−0.6 (−4.5 to 3.3)	RR, 0.86 (0.35 to 2.14)
Asthma worseninge	18,22	710	259	589	312	−10.2 (−21.5 to 1.2)	RR, 0.78 (0.72 to 0.86)	High
Death
All-cause	18,22	710	0	589	0	No deaths occurred		Insufficient
Asthma-specific	18,22	710	0	589	0	No deaths occurred		Insufficient
Asthma Control
ACQ-5 responderf	26	453	NR	454	NR		OR, 1.42 (1.08 to 1.86)	Low
ACQ-6 scoref	28	256	1.23 (0.80)	132	1.14 (0.79)		MD, 0.09 (−0.08 to 0.25)	Low
ACQ-6 responderf	28	257	191	135	100	0.2 (−8.5 to 9.6)	RR, 1.00 (0.88 to 1.12)	Low
ACQ-7 scoref	26,28	711		590			MD, −0.07 (−0.31 to 0.18)	Moderate
ACQ-7 respondera,f	26	453	263	454	205	12.9 (6.4 to 19.3)	RR, 1.28 (1.13 to 1.46)
	28	257	190	135	99	0.6 (−8.2 to 10.1)	RR, 1.01 (0.89 to 1.14)	Moderate
Spirometry
FEV1 peak, L	26,28	709		586			MD, 0.11 (0.00 to 0.22)	Moderate
FEV1 trough, L	26,28	709		586			MD, 0.07 (0.01 to 0.14)	Moderate
FEV1 AUC, L	26,28	709		586			MD, 0.10 (0.01 to 0.19)	High
FVC peak, L	26,28	709		586			MD, 0.11 (0.05 to 0.17)	High
FVC trough, L	26,28	709		586			MD, 0.09 (0.03 to 0.15)	High
FVC AUC, L	26,28	709		586			MD, 0.10 (0.04 to 0.17)	High
Asthma-Related Quality of Life
AQLQ scorea,g	Trial 126	237	5.15 (0.89)	222	5.11 (0.89)		MD, 0.04 (−0.13 to 0.20)	High
	Trial 226	216	5.09 (0.91)	232	4.95 (0.91)		MD, 0.14 (−0.03 to 0.31)
AQLQ responderg	26	453	212	454	192	4.5 (−2.0 to 10.9)	RR, 1.11 (0.96 to 1.28)	Moderate
Health Resource Utilization
Rescue medication use, puffs/24h	26,28	707		585			MD, −0.12 (−0.42 to 0.17)	Moderate

Abbreviations: ACQ, Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire; AUC, area under the curve; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; LAMA, long-acting muscarinic antagonist; MD, mean difference; NR, not reported, OR, odds ratio; RR, relative risk.

^a Meta-analyses were performed when ≥3 studies reported the same outcome. When data were available for ≤2 studies, the results from each study are individually shown. For continuous outcomes, the mean value represents the mean change from baseline (change score) for each study group and the MD represents the difference in change scores (change from baseline) between the LAMA and control groups.

^b Data are presented as either number of participants with an event (for dichotomous end points) or mean (SD) value (for continuous end points).

^c Data are presented as absolute risk differences (risk in LAMA group minus risk in control group) between groups.

^d The strength of evidence for each study was based on 5 domains (risk of bias, consistency, directness, precision, and publication bias) and categorized as high, moderate, low, or insufficient (eAppendix B in the Supplement).

^e Defined by studies as a progressive increase in asthma symptoms compared with day-to-day symptoms or a decrease in morning peak expiratory flow of ≥30% for ≥2 d.

^f ACQ responder was defined as an individual who had their score improve by ≥0.5 points.⁶ ACQ (range, 0 [worse] to 6 [better control]) is a patient self-administered tool for assessing overall asthma control. The minimal important difference is a 0.5-point change.^6,30,31

^g AQLQ (range, 1 [severe impairment] to 7 [no impairment]) is an asthma-specific quality of life tool. The minimal important difference is a 0.5-point change.^7,32,33,34 AQLQ responder was defined as an individual who had their score improve by ≥0.5 points .⁷