Prevention of clinically important deteriorations in COPD with umeclidinium/vilanterol

Abstract

BackgroundMinimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.MethodsThis study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations. Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.ResultsIn Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%). The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001). In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%). UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).ConclusionThis exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods. UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy.

Assessing Short-term Deterioration in Maintenance-naïve Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials

“…The current study focused on patients from three similar studies with a large proportion of symptomatic COPD patients (all mMRC ≥2), 55% and 45% of the ITT and MN subgroups, respectively, presenting with severe lung function impairment at baseline. The current findings are commensurate with the earlier study by Singh and colleagues [15], highlighting that reducing the risk of a first CID is as likely in low and high risk patients and when using dual bronchodilators as first- or second-line therapy. It is therefore important that the early use of dual therapy was compared with monotherapy in this MN population.…”

“…A recent study has demonstrated the dual bronchodilator therapy may reduce the risk of short-term CID and potentially provide greater airway stability compared with monotherapy [15]. …”

“…In support of this, early maintenance treatment with TIO was shown to be associated with long-term sustained benefits in the 4-year UPLIFT study, with a slower decline in lung function and HRQoL [3, 18]. In a previous publication, which examined time to a first CID with UMEC/VI versus TIO and placebo in both GOLD B and D subgroups, no apparent differences were found in the magnitude of treatment benefit on the incidence of CID based on levels of lung function impairment or disease severity at baseline [15]. The current study focused on patients from three similar studies with a large proportion of symptomatic COPD patients (all mMRC ≥2), 55% and 45% of the ITT and MN subgroups, respectively, presenting with severe lung function impairment at baseline.…”

Umeclidinium/Vilanterol Versus Tiotropium/Olodaterol in Maintenance-Naïve Patients with Moderate Symptomatic Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis

“…However, LAMA/LABA bronchodilation appear to be similarly beneficial compared with LAMA monotherapy in symptomatic patients who have or have not previously received a COPD maintenance treatment, which questions the rationale for a delayed stepwise approach in managing persistent symptoms [16,17]. There is also evidence that early use of LAMA/LABA combinations may improve disease stability compared with LAMA monotherapy by protecting symptomatic patients, including maintenance-naïve (MN) patients, from further disease deterioration [16,[18][19][20]. Dual therapy could therefore provide the opportunity for maximal bronchodilation, with a view to minimizing daily symptoms, improving quality of life (QoL), and preventing further disease deterioration.…”

GOLD 2017 recommendations for COPD patients: toward a more personalized approach

“…Group B patients should be started on single bronchodilator, either LAMA or LABA, while the LAMA/LABA combination may be started soon in the more symptomatic patients. Accordingly, a recent exploratory analysis, showed that the LAMA/LABA combination was superior to placebo and monotherapy in symptomatic patients with low exacerbation risk [42]. ICS in not recommended alone nor as an addition to either LAMA or LABA in group B.…”