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. 2018 Oct;35(10):1626-1638.
doi: 10.1007/s12325-018-0771-4. Epub 2018 Sep 6.

Preventing Clinically Important Deterioration of COPD with Addition of Umeclidinium to Inhaled Corticosteroid/Long-Acting β2-Agonist Therapy: An Integrated Post Hoc Analysis

Ian P Naya  1 , Lee Tombs  2 , David A Lipson  3 , Chris Compton  4
Affiliations

Preventing Clinically Important Deterioration of COPD with Addition of Umeclidinium to Inhaled Corticosteroid/Long-Acting β2-Agonist Therapy: An Integrated Post Hoc Analysis

Ian P Naya et al. Adv Ther. 2018 Oct.

Abstract

Introduction: Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD). This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.

Methods: This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2). A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George's Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation. Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy. Adverse events (AEs) were also assessed.

Results: Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818). Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001). Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population. No significant reduction in risk of a SGRQ CID was observed. AE incidence was similar between treatment groups.

Conclusion: Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations. Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.

Funding: GlaxoSmithKline (study number: 202067). Plain language summary available for this article.

Keywords: Add-on LAMA; COPD; Clinically important deteriorations; Fluticasone furoate/vilanterol; Fluticasone propionate/salmeterol; Respiratory; Triple therapy; Umeclidinium.

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Conflict of interest statement

Ian P. Naya is an employee of GSK and holds stocks and shares in GSK. David A. Lipson is an employee of GSK and holds stocks and shares in GSK. Chris Compton is an employee of GSK and holds stocks and shares in GSK. Lee Tombs is a contingent worker on assignment at GSK. ELLIPTA and DISKUS are owned by or licensed to the GSK group of companies.

Figures

Fig. 1
Fig. 1
Analysis of CIDs in the ITT population. a Type of deterioration; b Kaplan–Meier plot of time to first composite CID. *HR and 95% CI based on a time to first event analysis using a Cox’s proportional hazards model. CI confidence interval, CID clinically important deterioration, FEV1 forced expiratory volume in 1 s, HR hazard ratio, ICS/LABA inhaled corticosteroid/long-acting β2-agonist, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium
Fig. 2
Fig. 2
Analysis of CIDs stratified by GOLD 2016 groupsa. aClassified by criteria presented in GOLD 2016 update [29]; definition included percent predicted FEV1 as a severity marker (i.e., patients could be included in Group D with an FEV1 < 50% predicted). *HR and 95% CI based on a time to first event analysis using a Cox’s proportional hazards model. CI confidence interval, CID clinically important deterioration, FEV1 forced expiratory volume in 1 s, HR hazard ratio, ICS/LABA inhaled corticosteroid/long-acting β2-agonist, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium
Fig. 3
Fig. 3
Analysis of CIDs stratified by exacerbation historya. aExacerbation-free patients were defined as those with no history of exacerbations requiring oral/systemic corticosteroids and/or antibiotics. *HR and 95% CI based on a time to first event analysis using a Cox’s proportional hazards model. CI confidence interval, CID clinically important deterioration, FEV1 forced expiratory volume in 1 s, HR hazard ratio, ICS/LABA inhaled corticosteroid/long-acting β2-agonist, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium
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