Cochrane · systematic review · CD013799
Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta‐analysis
Oba, Y, Anwer, S, Maduke, T, et al. · Cochrane Database of Systematic Reviews · 2022 · Cochrane Library
AirwaysAMSTAR 2: not assessed
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
161
current version
GRADE rated
128
No studies
15
Included studies
NR
No studies 15 · 9.3%Ungraded 18 · 11.2%Very low 4 · 2.5%Low 26 · 16.1%Moderate 74 · 46%High 24 · 14.9%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
NMA Summary of Findings for severe exacerbations (asthma‐related hospitalisations)
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Severe exacerbations Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 8 RCTs Total Participants: 9983 | no estimate extracted | 8 studies · 9983 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 7 RCTs; 7023 participants) | no estimate extracted | 7 studies · 7023 participants | Moderate |
MD‐TRIPLE (Direct evidence; 2 RCTs; 1023 participants) | no estimate extracted | 2 studies · 1023 participants | Low |
HD‐TRIPLE (Direct evidence; 2 RCTs; 1024 participants) | no estimate extracted | 2 studies · 1024 participants | Low |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
Asthma exacerbations ‐ pairwise comparisons
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome№ of participants(studies) | no estimate extracted | NR | No studies |
Severe exacerbations ‐ HD‐ICA/LABA vs MD‐ICS LABA№ of participants: 4492(5 RCTs) | RR 1.49 [0.74, 3.01] | 5 studies · 4492 participants | Moderate |
Severe exacerbations ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 813(1 RCT) | RR 1 [0.35, 2.83] | 1 study · 813 participants | Low |
Severe exacerbations ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 815(1 RCT) | RR 0.57 [0.17, 1.93] | 1 study · 815 participants | Low |
Severe exacerbations ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 812(1 RCT) | RR 1.4 [0.45, 4.37] | 1 study · 812 participants | Low |
Severe exacerbations ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 1727(2 RCTs) | RR 0.8 [0.45, 1.42] | 2 studies · 1727 participants | Moderate |
Severe exacerbations ‐ HD TRIPLE vs MD TRIPLE№ of participants: 814(1 RCT) | RR 0.57 [0.17, 1.93] | 1 study · 814 participants | Low |
Severe exacerbations ‐ TRIPLE vs DUAL№ of participants: 2540(2 RCTs) | RR 0.84 [0.51, 1.4] | 2 studies · 2540 participants | Moderate |
Moderate to severe exacerbations ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 5452(6 RCTs) | RR 0.93 [0.82, 1.05] | 6 studies · 5452 participants | High |
Moderate to severe exacerbations ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3184(3 RCTs) | RR 0.86 [0.75, 0.99] | 3 studies · 3184 participants | Moderate |
Moderate to severe exacerbations ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 2037(2 RCTs) | RR 0.78 [0.66, 0.92] | 2 studies · 2037 participants | High |
Moderate to severe exacerbations ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2651(2 RCTs) | RR 1.05 [0.78, 1.41] | 2 studies · 2651 participants | Low |
Moderate to severe exacerbations ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 4989(4 RCTs) | RR 0.83 [0.75, 0.92] | 4 studies · 4989 participants | High |
Moderate to severe exacerbations ‐ HD TRIPLE vs MD TRIPLE№ of participants: 3470(3 RCTs) | RR 0.85 [0.72, 1.01] | 3 studies · 3470 participants | Moderate |
Moderate to severe exacerbations ‐ TRIPLE vs DUAL№ of participants: 8173(5 RCTs) | RR 0.85 [0.78, 0.92] | 5 studies · 8173 participants | High |
NMA Summary of Findings for moderate to severe (steroid‐requiring) exacerbations
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Moderate to severe exacerbations Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 10 RCTs Total Participants: 12407 | no estimate extracted | 10 studies · 12407 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 6 RCTs; 5452 participants) | no estimate extracted | 6 studies · 5452 participants | High |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3184 participants) | no estimate extracted | 3 studies · 3184 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 2037 participants) | no estimate extracted | 2 studies · 2037 participants | High |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
HD Triple vs. MD Triple | no estimate extracted | NR | No studies |
HD‐TRIPLE (Direct evidence; 3 RCTs; 3470 participants) | no estimate extracted | 3 studies · 3470 participants | Moderate |
MD Triple | no estimate extracted | NR | No studies |
NMA Summary of Findings for change from baseline in ACQ scores at 3 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Change from baseline in ACQ scores at 3 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 4 RCTs Total Participants: 4529 | no estimate extracted | 4 studies · 4529 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 3 RCTs; 2450 participants) | no estimate extracted | 3 studies · 2450 participants | Moderate |
MD‐TRIPLE (Direct evidence; 1 RCT; 768 participants) | no estimate extracted | 1 study · 768 participants | Low |
HD‐TRIPLE (Direct evidence; 1 RCT; 764 participants) | no estimate extracted | 1 study · 764 participants | Low |
MD‐ICS/LABA | 1 | NR | Ungraded |
NMA Summary of Findings for change from baseline in ACQ scores at 6 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Change from baseline in ACQ scores at 6 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 6 RCTs Total Participants: 7957 | no estimate extracted | 6 studies · 7957 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 3 RCTs; 3762 participants) | no estimate extracted | 3 studies · 3762 participants | Moderate |
MD‐TRIPLE (Direct evidence; 2 RCTs; 1961 participants) | no estimate extracted | 2 studies · 1961 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 1952 participants) | no estimate extracted | 2 studies · 1952 participants | Moderate |
MD‐ICS/LABA | 1 | NR | Ungraded |
NMA Summary of Findings for change from baseline in ACQ scores at 12 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Change from baseline in ACQ scores at 12 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 5 RCTs Total Participants: 5440 | no estimate extracted | 5 studies · 5440 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 3 RCTs; 3152 participants) | no estimate extracted | 3 studies · 3152 participants | Moderate |
MD‐TRIPLE (Direct evidence; 2 RCTs; 1366 participants) | no estimate extracted | 2 studies · 1366 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 1379 participants) | no estimate extracted | 2 studies · 1379 participants | Moderate |
MD‐ICS/LABA | 1 | NR | Ungraded |
Asthma Control Questionnaire: change from baseline ‐ pairwise comparisons ‡
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome№ of participants(studies) | no estimate extracted | NR | No studies |
CFB in ACQ at 3 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 2450(3 RCTs) | no estimate extracted | 3 studies · 2450 participants | Moderate |
CFB in ACQ at 3 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 768(1 RCT) | no estimate extracted | 1 study · 3 participants | Low |
CFB in ACQ at 3 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 764(1 RCT) | no estimate extracted | 1 study · 3 participants | Low |
CFB in ACQ at 3 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 771(1 RCT) | no estimate extracted | 1 study · 3 participants | Low |
CFB in ACQ at 3 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 767(1 RCT) | no estimate extracted | 1 study · 3 participants | Low |
CFB in ACQ at 3 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 2079(2 RCTs) | no estimate extracted | 2 studies · 3 participants | Moderate |
CFB in ACQ at 3 months ‐ TRIPLE vs DUAL№ of participants: 1535(1 RCT) | no estimate extracted | 1 study · 3 participants | Moderate |
CFB in ACQ at 6 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 3762(3 RCTs) | no estimate extracted | 3 studies · 6 participants | Moderate |
CFB in ACQ at 6 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 1961(2 RCTs) | no estimate extracted | 2 studies · 6 participants | Moderate |
CFB in ACQ at 6 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 1952(2 RCTs) | no estimate extracted | 2 studies · 6 participants | Moderate |
CFB in ACQ at 6 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2561(2 RCTs) | no estimate extracted | 2 studies · 6 participants | Moderate |
CFB in ACQ at 6 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 3459(3 RCTs) | no estimate extracted | 3 studies · 6 participants | Low |
CFB in ACQ at 6 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 3288(3 RCTs) | no estimate extracted | 3 studies · 6 participants | Moderate |
CFB in ACQ at 6 months ‐ TRIPLE vs DUAL№ of participants: 5408(4 RCTs) | no estimate extracted | 4 studies · 6 participants | Moderate |
CFB in ACQ at 12 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 3152(3 RCTs) | no estimate extracted | 3 studies · 12 participants | Low |
CFB in ACQ at 12 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 1366(2 RCTs) | no estimate extracted | 2 studies · 12 participants | Moderate |
CFB in ACQ at 12 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 1379(2 RCTs) | no estimate extracted | 2 studies · 12 participants | Moderate |
CFB in ACQ at 12 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 1967(2 RCTs) | no estimate extracted | 2 studies · 12 participants | Low |
CFB in ACQ at 12 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 2887(3 RCTs) | no estimate extracted | 3 studies · 12 participants | Moderate |
CFB in ACQ at 12 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 1381(2 RCTs) | no estimate extracted | 2 studies · 12 participants | Moderate |
CFB in ACQ at 12 months ‐ DUAL vs TRIPLE№ of participants: 4253(4 RCTs) | no estimate extracted | 4 studies · 12 participants | Moderate |
NMA Summary of Findings for change from baseline in AQLQ scores at 6 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Change from baseline in AQLQ score at 6 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 4 RCTs Total Participants: 3454 | no estimate extracted | 4 studies · 3454 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 1 RCT; 1223 participants) | no estimate extracted | 1 study · 1223 participants | Moderate |
MD‐TRIPLE (Direct evidence; 0 RCTs; 0 participants) | no estimate extracted | 0 studies · 0 participants | Low |
HD‐TRIPLE (Direct evidence; 0 RCTs; 0 participants) | no estimate extracted | 0 studies · 0 participants | Low |
MD‐ICS/LABA | 1 | NR | Ungraded |
NMA Summary of Findings for change from baseline in AQLQ scores at 12 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Change from baseline in AQLQ score at 12 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 4 RCTs Total Participants: 4809 | no estimate extracted | 4 studies · 4809 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 2 RCTs; 2815 participants) | no estimate extracted | 2 studies · 2815 participants | Moderate |
MD‐TRIPLE (Direct evidence; 1 RCT; 1071 participants) | no estimate extracted | 1 study · 1071 participants | Moderate |
HD‐TRIPLE (Direct evidence; 1 RCT; 1088 participants) | no estimate extracted | 1 study · 1088 participants | Moderate |
MD‐ICS/LABA | 1 | NR | Ungraded |
Asthma Quality of Life Questionnaire: change from baseline ‐ pairwise comparisons ‡
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome№ of participants(studies) | no estimate extracted | NR | No studies |
CFB in AQLQ at 6 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 1223(1 RCT) | no estimate extracted | 1 study · 6 participants | Moderate |
CFB in AQLQ at 6 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 907(2 RCTs) | no estimate extracted | 2 studies · 6 participants | Low |
CFB in AQLQ at 6 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 1426(1 RCT) | no estimate extracted | 1 study · 6 participants | Moderate |
CFB in AQLQ at 6 months ‐ TRIPLE vs DUAL№ of participants: 907(2 RCTs) | no estimate extracted | 2 studies · 6 participants | Low |
CFB in AQLQ at 12 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 2815(2 RCTs) | no estimate extracted | 2 studies · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 1071(1 RCT) | no estimate extracted | 1 study · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 1088(1 RCT) | no estimate extracted | 1 study · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 1628(1 RCT) | no estimate extracted | 1 study · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 2552(3 RCTs) | no estimate extracted | 3 studies · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 1087(1 RCT) | no estimate extracted | 1 study · 12 participants | Moderate |
CFB in AQLQ at 12 months ‐ TRIPLE vs DUAL№ of participants: 3623(3 RCTs) | no estimate extracted | 3 studies · 12 participants | Moderate |
NMA Summary of Findings for ACQ responders at 6 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: ACQ responders at 6 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 7 RCTs Total Participants: 10453 | no estimate extracted | 7 studies · 10453 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 3 RCTs; 3700 participants) | no estimate extracted | 3 studies · 3700 participants | Moderate |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3063 participants) | no estimate extracted | 3 studies · 3063 participants | Low |
HD‐TRIPLE (Direct evidence; 2 RCTs; 1916 participants) | no estimate extracted | 2 studies · 1916 participants | Low |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
NMA Summary of Findings for ACQ responders at 12 months
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: ACQ responders at 12 months
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 5 RCTs Total Participants: 7391 | no estimate extracted | 5 studies · 7391 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 2 RCTs; 2817 participants) | no estimate extracted | 2 studies · 2817 participants | Moderate |
MD‐TRIPLE (Direct evidence; 2 RCTs; 2237 participants) | no estimate extracted | 2 studies · 2237 participants | Moderate |
HD‐TRIPLE (Direct evidence; 1 RCT; 1088 participants) | no estimate extracted | 1 study · 1088 participants | Moderate |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
Asthma Control Questionnaire responders ‐ pairwise comparisons
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome№ of participants(studies) | no estimate extracted | NR | No studies |
ACQ responders at 6 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 3700(3 RCTs) | RR 1.02 [0.96, 1.08] | 3 studies · 6 participants | Moderate |
ACQ responders at 6 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3063(3 RCTs) | RR 1.09 [0.99, 1.19] | 3 studies · 6 participants | Low |
ACQ responders at 6 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 1916(2 RCTs) | RR 1.11 [0.91, 1.35] | 2 studies · 6 participants | Very low |
ACQ responders at 6 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2480(2 RCTs) | RR 1.02 [0.97, 1.08] | 2 studies · 6 participants | Moderate |
ACQ responders at 6 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 4818(4 RCTs) | RR 1.07 [1.01, 1.14] | 4 studies · 6 participants | Moderate |
ACQ responders at 6 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 2821(3 RCTs) | RR 0.99 [0.95, 1.03] | 3 studies · 6 participants | Moderate |
ACQ responders at 6 months ‐ TRIPLE vs DUAL№ of participants: 7881(5 RCTs) | RR 1.09 [1.02, 1.15] | 5 studies · 6 participants | Low |
ACQ responders at 12 months ‐ HD‐ICS/LABA vs MD‐ICS/LABA№ of participants: 2817(2 RCTs) | RR 0.99 [0.9, 1.07] | 2 studies · 12 participants | Low |
ACQ responders at 12 months ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 2222(2 RCTs) | RR 1.01 [0.95, 1.07] | 2 studies · 12 participants | Moderate |
ACQ responders at 12 months ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 1088(1 RCT) | RR 1.08 [1.01, 1.15] | 1 study · 12 participants | Moderate |
ACQ responders at 12 months ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 1631(1 RCT) | RR 0.97 [0.91, 1.03] | 1 study · 12 participants | Moderate |
ACQ responders at 12 months ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 3982(3 RCTs) | RR 1.11 [0.99, 1.23] | 3 studies · 12 participants | Very low |
ACQ responders at 12 months ‐ HD TRIPLE vs MD TRIPLE№ of participants: 1089(1 RCT) | RR 1.08 [1.01, 1.16] | 1 study · 12 participants | Moderate |
ACQ responders at 12 months ‐ TRIPLE vs DUAL№ of participants: 6204(4 RCTs) | RR 1.07 [0.99, 1.17] | 4 studies · 12 participants | Very low |
NMA Summary of Findings for all‐cause SAEs
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: All‐cause serious adverse events (SAEs) Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 13 RCTs Total Participants: 144476 | no estimate extracted | 13 studies · 144476 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 8 RCTs; 7511 participants) | no estimate extracted | 8 studies · 7511 participants | High |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3187 participants) | no estimate extracted | 3 studies · 3187 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCT; 2039 participants) | no estimate extracted | 2 studies · 2039 participants | Moderate |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
Serious adverse events, adverse events, and dropouts due to adverse event ‐ pairwise comparisons
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome№ of participants(studies) | no estimate extracted | NR | No studies |
All cause SAEs ‐ HD‐ICS/LABA vs MD‐ICS LABA№ of participants: 7511(8 RCTs) | RR 1.03 [0.83, 1.29] | 8 studies · 7511 participants | High |
All cause SAEs ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3187(3 RCTs) | RR 1.13 [0.85, 1.5] | 3 studies · 3187 participants | Moderate |
All cause SAEs ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 2039(2 RCTs) | RR 1.05 [0.76, 1.47] | 2 studies · 2039 participants | Moderate |
All cause SAEs ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2660(2 RCTs) | RR 1.08 [0.81, 1.44] | 2 studies · 2660 participants | Moderate |
All cause SAEs ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 5004(4 RCTs) | RR 0.95 [0.77, 1.18] | 4 studies · 5004 participants | Moderate |
All cause SAEs ‐ HD TRIPLE vs MD TRIPLE№ of participants: 2998(3 RCTs) | RR 0.96 [0.72, 1.27] | 3 studies · 2998 participants | Moderate |
All cause SAEs ‐ TRIPLE vs DUAL№ of participants: 8192(6 RCTs) | RR 1.03 [0.87, 1.21] | 6 studies · 8192 participants | High |
Asthma‐related SAEs ‐ HD‐ICS/LABA vs MD‐ICS LABA№ of participants: 6244(6 RCTs) | RR 1.33 [0.8, 2.21] | 6 studies · 6244 participants | High |
Asthma‐related SAEs ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3188(3 RCTs) | RR 1.52 [0.85, 2.69] | 3 studies · 3188 participants | Moderate |
Asthma‐related SAEs ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 2039(2 RCTs) | RR 0.86 [0.41, 1.8] | 2 studies · 2039 participants | High |
Asthma‐related SAEs ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2660(2 RCTs) | RR 1.35 [0.77, 2.36] | 2 studies · 2660 participants | Moderate |
Asthma‐related SAEs ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 5004(4 RCTs) | RR 0.86 [0.58, 1.27] | 4 studies · 5004 participants | High |
Asthma‐related SAEs ‐ HD TRIPLE vs MD TRIPLE№ of participants: 3472(3 RCTs) | RR 0.57 [0.31, 1.05] | 3 studies · 3472 participants | High |
Asthma‐related SAEs ‐ TRIPLE vs DUAL№ of participants: 8192(6 RCTs) | RR 1.04 [0.76, 1.42] | 6 studies · 8192 participants | High |
All cause AEs ‐ HD‐ICS/LABA vs MD‐ICS LABA№ of participants: 5949(7 RCTs) | RR 1.01 [0.97, 1.06] | 7 studies · 5949 participants | High |
All cause AEs ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3188(3 RCTs) | RR 0.96 [0.91, 1] | 3 studies · 3188 participants | Moderate |
All cause AEs ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 2039(2 RCTs) | RR 0.92 [0.85, 1] | 2 studies · 2039 participants | Moderate |
All cause AEs ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2659(2 RCTs) | RR 0.99 [0.83, 1.18] | 2 studies · 2659 participants | Low |
All cause AEs ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 5004(4 RCTs) | RR 0.91 [0.87, 0.96] | 4 studies · 5004 participants | High |
All cause AEs ‐ HD TRIPLE vs MD TRIPLE№ of participants: 3473(3 RCTs) | RR 0.95 [0.9, 1.02] | 3 studies · 3473 participants | Moderate |
All cause AEs ‐ TRIPLE vs DUAL№ of participants: 8192(6 RCTs) | RR 0.93 [0.9, 0.96] | 6 studies · 8192 participants | High |
Dropouts due to adverse event ‐ HD‐ICS/LABA vs MD‐ICS LABA№ of participants: 5969(7 RCTs) | RR 1 [0.68, 1.48] | 7 studies · 5969 participants | High |
Dropouts due to adverse event ‐ MD TRIPLE vs MD‐ICS/LABA№ of participants: 3205(3 RCTs) | RR 0.42 [0.08, 2.14] | 3 studies · 3205 participants | Very low |
Dropouts due to adverse event ‐ HD TRIPLE vs MD‐ICS/LABA№ of participants: 2670(2 RCTs) | RR 0.47 [0.19, 1.18] | 2 studies · 2670 participants | Moderate |
Dropouts due to adverse event ‐ MD TRIPLE vs HD‐ICS/LABA№ of participants: 2668(2 RCTs) | RR 1.24 [0.76, 2.02] | 2 studies · 2668 participants | Moderate |
Dropouts due to adverse event ‐ HD TRIPLE vs HD‐ICS/LABA№ of participants: 5018(4 RCTs) | RR 0.6 [0.38, 0.95] | 4 studies · 5018 participants | High |
Dropouts due to adverse event ‐ HD TRIPLE vs MD TRIPLE№ of participants: 1765(2 RCTs) | RR 1 [0.29, 3.44] | 2 studies · 1765 participants | Moderate |
Dropouts due to adverse event ‐ TRIPLE vs DUAL№ of participants: 8223(5 RCTs) | RR 0.59 [0.33, 1.03] | 5 studies · 8223 participants | Moderate |
NMA Summary of Findings for asthma‐related SAEs
Population: Adolescent sand adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Asthma‐related serious adverse events (SAEs) Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 11 RCTs Total Participants: 13209 | no estimate extracted | 11 studies · 13209 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 6 RCTs; 6244 participants) | no estimate extracted | 6 studies · 6244 participants | High |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3188 participants) | no estimate extracted | 3 studies · 3188 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 2039 participants) | no estimate extracted | 2 studies · 2039 participants | High |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
NMA Summary of Findings for all‐cause AEs
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: All‐cause adverse events (AEs) Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 12 RCTs Total Participants: 12915 | no estimate extracted | 12 studies · 12915 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 7 RCTs; 5949 participants) | no estimate extracted | 7 studies · 5949 participants | High |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3188 participants) | no estimate extracted | 3 studies · 3188 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 2039 participants) | no estimate extracted | 2 studies · 2039 participants | High |
MD‐ICS/LABA | no estimate extracted | NR | No studies |
NMA summary of findings table for dropouts due to AEs
Population: Adolescents and adults with symptomatic asthma Interventions: HD‐ICS/LABA, MD‐TRIPLE, HD‐TRIPLE Comparator (reference): Medium‐Dose ICS/LABA (MD‐ICS/LABA) Outcome: Dropouts due to adverse events (AEs) Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total studies: 12 RCTs Total Participants: 12915 | no estimate extracted | 12 studies · 12915 participants | Ungraded |
HD‐ICS/LABA (Direct evidence; 7 RCTs; 5969 participants) | no estimate extracted | 7 studies · 5969 participants | High |
MD‐TRIPLE (Direct evidence; 3 RCTs; 3205 participants) | no estimate extracted | 3 studies · 3205 participants | Moderate |
HD‐TRIPLE (Direct evidence; 2 RCTs; 2051 participants) | no estimate extracted | 2 studies · 2051 participants | Moderate |
MD‐ICS/LABA | no estimate extracted | NR | No studies |