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

Abstract

IntroductionDual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.MethodsThis post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV1). St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.ResultsUMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102–189) and ITT: 95 ml (71–118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51–0.85); ITT: 0.62 (0.54–0.71), both P ≤ 0.001]. Adverse events were similar across both populations and treatments.ConclusionsEarly use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD. Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115). Funding: This study was funded by GSK.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users.

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

“…Importantly, the treatment difference between the LAMA/LABA combinations observed in this study was greater in magnitude than that reported with TIO/OLO versus TIO alone in a similar MN population in the replicate OTEMTO studies [17]. Using dual therapy as a first-line maintenance therapy has been shown to provide the opportunity for improved bronchodilation and therefore potential for optimal symptom management and greater protection against further disease deterioration [16][17][18]. The greater lung function improvements with UMEC/VI over TIO/OLO in this MN population suggest that there is no ceiling to bronchodilation potential in patients with moderate COPD.…”

“…Furthermore, demonstration of a statistically significant treatment difference on supplemental rescue medication use, a clinical endpoint reflecting an effect on symptoms [36], shows that the potential for better symptom control with improved bronchodilation in MN patients is also a realistic goal. Currently, data on the impact of initiating maintenance therapy with dual bronchodilators in MN patients are sparse and are largely obtained using post hoc analysis of prospectively collected data [16,17,24]. These analyses consistently indicate no diminished patient benefit or safety concern when opting to use dual therapy as a first-line treatment option.…”

“…Permitted treatment included short-acting bronchodilators, anti-infectives (antibiotics, antifungals, antivirals, antiseptics), acute exacerbation treatment, and oxygen therapy. These criteria have been used previously to define MN populations in studies comparing UMEC/VI with TIO in patients with COPD [16,17].…”

“…As such, LAMA/LABA combination therapy is recommended as initial therapy in most patients with persistent COPD symptoms [1]. 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].…”

Indacaterol/glycopyrronium versus tiotropium or glycopyrronium in long‐acting bronchodilator‐naïve COPD patients: A pooled analysis

“…Treatment with LABA/LAMA is recommended based on its superior results versus standard of care therapy with LAMA monotherapy or LABA/inhaled corticosteroid (ICS), and lower risk of development of pneumonia versus ICS‐containing treatment . Dual bronchodilator therapy with fixed‐dose LABA/LAMA has demonstrated improvements in lung function and health‐related quality of life, and has reduced the usage of rescue medication in patients with prior maintenance therapy with a single bronchodilator …”