Are inhalers containing umeclidinium bromide effective and safe for people with COPD?

Review question

We reviewed the effectiveness and safety of umeclidinium inhalers compared with placebo (dummy) inhalers in people with chronic obstructive pulmonary disease (COPD).

Background

People with COPD are often breathless and have poor quality of life. Symptoms may worsen during flare-ups, increasing healthcare expenses and reducing life span. Medications that widen the airways (bronchodilators), which act for 12 to 24 hours, are the treatments generally given to improve symptoms. Umeclidinium is a new treatment of this sort. We wanted to discover whether umeclidinium was better or worse than placebo.

Study characteristics

We included four studies involving 3798 people with COPD. Most were men in their 60s who were moderate to heavy smokers. When they started treatment, they had moderate to severe symptoms of COPD. Studies ranged from three months to one year long. Studies were well designed and were funded by the drug manufacturer. Neither people in the study nor people doing the research knew which treatment participants were getting. People in the studies took either umeclidinium or placebo through an inhaler each morning.

The conclusions of this review are current to April 2017.

Key results

We determined the number of people who had a moderate flare-up. A moderate flare-up is treated with short-term oral steroids or antibiotics, or both. People who took umeclidinium were less likely than those given placebo to have a moderate flare-up. Eighteen people with COPD would need to be treated with umeclidinium to prevent one of these flare-ups.

People taking umeclidinium probably had a better quality of life, and their lung function was better. People taking umeclidinium were less breathless and took fewer puffs of their reliever inhaler.

Results showed little or no difference with umeclidinium in other outcomes, such as risk of dying during the study period, side effects, or the need to be admitted to hospital because of severe flare-ups.

Quality of the evidence

We are confident that umeclidinium inhalers are more likely than dummy inhalers to reduce moderate flare-ups and improve symptoms and lung function. However, we are less certain about effects of umeclidinium on quality of life, side effects, and serious side effects. We have limited confidence in terms of hospital admissions due to flare-ups, but this was a rare event.

Conclusions

In people with COPD, umeclidinium inhalers improve symptoms, lung function, and quality of life compared with dummy inhalers. They also reduce the use of quick-relief medications and decrease flare-ups that need additional medication. However, no convincing evidence indicates that umeclidinium is better than dummy inhalers in terms of hospitalisations, side effects, serious side effects, or deaths.

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.

Read the full 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 strategy: 

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).

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