Näytönastekatsaukset

ICS/LABA/LAMA versus LABA/LAMA in treatment of COPD

Näytönastekatsaukset

4.11.2026

Ilona Mikkola

Level of evidence: B

ICS/LABA/LAMA reduces exacerbations and all-cause mortality, and improves health-related quality of life when compared to LABA/LAMA in symptomatic COPD patients with previous exacerbation.

The quality of evidence is moderate (downgraded due to indirectness and imprecision). The evidence is applicable in Finland. An increased risk of pneumonia is a potentially serious adverse effect. Cost outcomes were not reported in the appraised study.

Table 1. Description of the included studies
Reference	Study type	Population	Intervention and comparison	Outcomes	Risk of bias «Additional comments for included studies»2
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; COPD= chronic obstructive pulmonary disease, ICS=inhaled corticosteroids; LABA= long‐acting bronchodilators including beta2-agonists, LAMA= muscarinic antagonists, SGRQ= St George's Respiratory Questionnaire
«van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Coc»1	SR and MA of RCTs (4 trials, n=15,412)	Adults with symptomatic COPD (mean age 64.4 to 65.3 years), symptomatic COPD (COPD Assessment Test Score ≥ 10), mostly severe–very severe airflow limitation (FEV1 <50%) and ≥1 exacerbation in previous year	Intervention: Triple inhaled therapy (ICS + LABA + LAMA) Comparison: Dual bronchodilation (LABA + LAMA)	exacerbations (moderate–severe, severe) health-related quality of life (SGRQ) mortality adverse events	Overall low risk of bias; some concerns for attrition and reporting bias in individual studies

Table 2. Additional comments for included studies
Reference	Comments
«van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Coc»1	Acute exacerbations of COPD were defined as "an acute worsening of COPD symptoms above normal day-to-day variation" in all four studies. Severity was rated according to the level of treatment: mild (shortacting bronchodilators), moderate (systemic glucocorticoids or antibiotics), or severe (hospitalisation or death, or both). Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies.

Results

Table 3. Health related quality of life (SGRQ) improvement of minimal clinically important difference (MCID) threshold (4-point decrease; lower scores indicate better health related quality of life)
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Relative effect (95% CI)
I= intervention; C=comparison; CI=confidence interval; OR=odds ratio
«van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Coc»1	3 and 14,070 (9136/4934)	52 weeks	3878/9136 (42.4%)	1741/4934 (35.3%)	OR 1.35, 95% CI 1.26 to 1.45. Translates to 71 more responders per 1000 treated with triple therapy (CI 54 more to 89 more).
Level of evidence: high

Table 4. COPD moderate or severe exacerbations
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Relative effect (95% CI)
I= intervention; C=comparison; CI=confidence interval; RR=risk ratio
«van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Coc»1	4 and 15,397 (9812 / 5585)	52 weeks	Mean rate ranged from 0.46 to 1.08 exacerbations per year.	Mean rate ranged from 0.59 to 1.42 exacerbations per year.	RR 0.74 (95% CI 0.67–0.81)
Level of evidence: moderate/low The quality of evidence is downgraded due to indirectness.

Table 5. All-cause mortality
Reference	Number of studies and number of patients (I/C)	Follow-up time	Absolute number of events (%) I	Absolute number of events (%) C	Relative effect (95% CI)
I= intervention; C=comparison; CI=confidence interval; OR=odds ratio
«van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Coc»1	4 and 15,397 (9812/5585)	52 weeks	139/9812 (1.4%)	112/5585 (2.0%)	OR 0.70 (0.54 to 0.90); Translates to 6 fewer deaths per 1000 treated with triple therapy (9 fewer to 2 fewer)
Level of evidence: moderate The quality of evidence is downgraded due to indirectness and imprecision.

References

van Geffen WH, Tan DJ, Walters JA, ym. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2023;12(12):CD011600 «PMID: 38054551»PubMed