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Review
, 6 (6), CD011897

Umeclidinium Bromide Versus Placebo for People With Chronic Obstructive Pulmonary Disease (COPD)

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Review

Umeclidinium Bromide Versus Placebo for People With Chronic Obstructive Pulmonary Disease (COPD)

Han Ni et al. Cochrane Database Syst Rev.

Abstract

Background: People with chronic obstructive pulmonary disease (COPD) have poor quality of life, reduced survival, and accelerated decline in lung function, especially associated with acute exacerbations, leading to high healthcare costs. Long-acting bronchodilators are the mainstay of treatment for symptomatic improvement, and umeclidinium is one of the new long-acting muscarinic antagonists approved for treatment of patients with stable COPD.

Objectives: To assess the efficacy and safety of umeclidinium bromide versus placebo for people with stable COPD.

Search methods: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, the World Health Organization (WHO) trials portal, and the GlaxoSmithKline (GSK) Clinical Study Register, using prespecified terms, as well as the reference lists of all identified studies. Searches are current to April 2017.

Selection criteria: We included randomised controlled trials (RCTs) of parallel design comparing umeclidinium bromide versus placebo in people with COPD, for at least 12 weeks.

Data collection and analysis: We used standard Cochrane methodological procedures. If we noted significant heterogeneity in the meta-analyses, we subgrouped studies by umeclidinium dose.

Main results: We included four studies of 12 to 52 weeks' duration, involving 3798 participants with COPD. Mean age of participants ranged from 60.1 to 64.6 years; most were males with baseline mean smoking pack-years of 39.2 to 52.3. They had moderate to severe COPD and baseline mean post-bronchodilator forced expiratory volume in one second (FEV1) ranging from 44.5% to 55.1% of predicted normal. As all studies were systematically conducted according to prespecified protocols, we assessed risk of selection, performance, detection, attrition, and reporting biases as low.Compared with those given placebo, participants in the umeclidinium group had a lesser likelihood of developing moderate exacerbations requiring a short course of steroids, antibiotics, or both (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.46 to 0.80; four studies, N = 1922; GRADE: high), but not specifically requiring hospitalisations due to severe exacerbations (OR 0.86, 95% CI 0.25 to 2.92; four studies, N = 1922, GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) to prevent an acute exacerbation requiring steroids, antibiotics, or both was 18 (95% CI 13 to 37). Quality of life was better in the umeclidinium group (mean difference (MD) -4.79, 95% CI -8.84 to -0.75; three studies, N = 1119), and these participants had a significantly higher chance of achieving a minimal clinically important difference of at least four units in St George's Respiratory Questionnaire (SGRQ) total score compared with those in the placebo group (OR 1.45, 95% CI 1.16 to 1.82; three studies, N = 1397; GRADE: moderate). The NNTB to achieve one person with a clinically meaningful improvement was 11 (95% CI 7 to 29). The likelihood of all-cause mortality, non-fatal serious adverse events (OR 1.33; 95% CI 0.89 to 2.00; four studies, N = 1922, GRADE: moderate), and adverse events (OR 1.06, 95% CI 0.85 to 1.31; four studies, N = 1922; GRADE: moderate) did not differ between umeclidinium and placebo groups. The umeclidinium group demonstrated significantly greater improvement in change from baseline in trough FEV1 compared with the placebo group (MD 0.14, 95% CI 0.12 to 0.17; four studies, N = 1381; GRADE: high). Symptomatic improvement was more likely in the umeclidinium group than in the placebo group, as determined by Transitional Dyspnoea Index (TDI) focal score (MD 0.76, 95% CI 0.43 to 1.09; three studies, N = 1193), and the chance of achieving a minimal clinically important difference of at least one unit improvement was significantly higher with umeclidinium than with placebo (OR 1.71, 95% CI 1.37 to 2.15; three studies, N = 1141; GRADE: high). The NNTB to attain one person with clinically important symptomatic improvement was 8 (95% CI 5 to 14). The likelihood of rescue medication usage (change from baseline in the number of puffs per day) was significantly less for the umeclidinium group than for the placebo group (MD -0.45, 95% CI -0.76 to -0.14; four studies, N = 1531).

Authors' conclusions: Umeclidinium reduced acute exacerbations requiring steroids, antibiotics, or both, although no evidence suggests that it decreased the risk of hospital admission due to exacerbations. Moreover, umeclidinium demonstrated significant improvement in quality of life, lung function, and symptoms, along with lesser use of rescue medications. Studies reported no differences in adverse events, non-fatal serious adverse events, or mortality between umeclidinium and placebo groups; however, larger studies would yield a more precise estimate for these outcomes.

Conflict of interest statement

HN: none known.

AH: none known.

SM: none known.

We are conducting this systematic review for academic purposes.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figure 3
Figure 3
Forest plot of comparison: 1 Umeclidinium bromide versus placebo, outcome: 1.1 Number of participants with exacerbations requiring steroids, antibiotics, or both.
Figure 4
Figure 4
Forest plot of comparison: 1 Umeclidinium bromide versus placebo, outcome: 1.2 Quality of life: change from baseline in SGRQ total score.
Figure 5
Figure 5
Forest plot of comparison: 1 Umeclidinium bromide versus placebo, outcome: 1.8 Number of participants with ≥ 1 unit improvement in TDI focal score.
Figure 6
Figure 6
Forest plot of comparison: 1 Umeclidinium bromide versus placebo, outcome: 1.13 Use of rescue medications (change from baseline in number of puffs per day).
Analysis 1.1
Analysis 1.1
Comparison 1 Umeclidinium bromide versus placebo, Outcome 1 Number of participants with exacerbations requiring steroids, antibiotics, or both.
Analysis 1.2
Analysis 1.2
Comparison 1 Umeclidinium bromide versus placebo, Outcome 2 Quality of life: change from baseline in SGRQ total score.
Analysis 1.3
Analysis 1.3
Comparison 1 Umeclidinium bromide versus placebo, Outcome 3 Quality of life: number of participants with ≥ 4 units improvement in SGRQ total score.
Analysis 1.4
Analysis 1.4
Comparison 1 Umeclidinium bromide versus placebo, Outcome 4 Non‐fatal serious adverse events.
Analysis 1.5
Analysis 1.5
Comparison 1 Umeclidinium bromide versus placebo, Outcome 5 Total number of deaths.
Analysis 1.6
Analysis 1.6
Comparison 1 Umeclidinium bromide versus placebo, Outcome 6 Number of participants with hospital admissions due to COPD exacerbation.
Analysis 1.7
Analysis 1.7
Comparison 1 Umeclidinium bromide versus placebo, Outcome 7 Improvement in symptoms: TDI focal score.
Analysis 1.8
Analysis 1.8
Comparison 1 Umeclidinium bromide versus placebo, Outcome 8 Number of participants with ≥ 1 unit improvement in TDI focal score.
Analysis 1.9
Analysis 1.9
Comparison 1 Umeclidinium bromide versus placebo, Outcome 9 Lung function: change from baseline in trough FEV1 (L).
Analysis 1.10
Analysis 1.10
Comparison 1 Umeclidinium bromide versus placebo, Outcome 10 Lung function: change from baseline in trough FVC (L).
Analysis 1.11
Analysis 1.11
Comparison 1 Umeclidinium bromide versus placebo, Outcome 11 Lung function: change from baseline in peak FEV1 (L).
Analysis 1.12
Analysis 1.12
Comparison 1 Umeclidinium bromide versus placebo, Outcome 12 Adverse events (not including serious adverse events).
Analysis 1.13
Analysis 1.13
Comparison 1 Umeclidinium bromide versus placebo, Outcome 13 Use of rescue medications (change from baseline in number of puffs per day).

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD011897

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