Evaluation of fluticasone propionate/salmeterol for the treatment of COPD: a systematic review.

Introduction: Recently, the generic formulation of FP/SAL FDC has been approved in COPD. Although FP/SAL FDC has been the first long-acting FDC approved in COPD, no systematic review assessed the effect of this combination for the treatment of COPD by considering specifically Phase IV studies. The aim of this review was to systematically assess the effect of FP/SAL FDC in COPD patients enrolled in Phase IV studies.Areas covered: The question of this systematic review was to examine the evidence regarding the impact of FP/SAL FDC for the treatment of COPD by searching for Phase IV studies in the ClinicalTrials.gov database.Expert opinion: Generic drugs represent an effective cost-saving step for health-care budgets in the treatment of COPD and should be used in agreement with current recommendations and prescription accuracy. FP/SAL FDC is recommended for the initiation therapy just in a small percentage of symptomatic patients that are at high risk of exacerbation with blood eosinophil counts ≥300 cells per µl. At follow-up, FP/SAL FDC can be escalated to triple ICS/LABA/LAMA combination or switched to LABA/LAMA combination by considering symptoms, exacerbations, lack of response to ICS, inappropriate original indication, and ICS-related adverse events such as pneumonia.

Real-world effectiveness of umeclidinium/vilanterol versus fluticasone propionate/salmeterol as initial maintenance therapy for chronic obstructive pulmonary disease (COPD): a retrospective cohort study.

Background and objective: Retrospective claims data in patients with chronic obstructive pulmonary disease (COPD) initiating maintenance therapy with inhaled fixed-dose combinations of long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) versus inhaled corticosteroid (ICS)/LABA have not been reported. Methods: Retrospective observational study in a COPD-diagnosed population of commercial and Medicare Advantage with Part D (MAPD) enrollees aged ≥40 years from a US health insurer database. Patients initiated umeclidinium/vilanterol (UMEC/VI [62.5/25 µg]) or fluticasone propionate/salmeterol (FP/SAL [250/50 µg]) between April 1, 2014 and August 31, 2016 (index date) and had 12 months continuous enrollment pre- and post-index. Exclusion criteria included an asthma diagnosis in the pre-index period/index date; ICS-, LABA-, or LAMA-containing therapy during the pre-index period; or pharmacy fills for both UMEC/VI and FP/SAL, multiple-inhaler triple therapy, a non-index therapy, or COPD exacerbation on the index date. Adherence (proportion of days covered [PDC] ≥80%) was modeled using weighted logistic regression following inverse probability of treatment weighting (IPTW). Weighted Kaplan-Meier and Cox proportional hazards regression following IPTW were performed for incidence of COPD exacerbation and escalation to multiple-inhaler triple therapy. Results: The study population included 5306 patients (1386 initiating UMEC/VI and 3920 initiating FP/SAL). Adjusted odds of adherence were 2.00 times greater among UMEC/VI than FP/SAL initiators (95% confidence interval [CI]: 1.62─2.46; P<0.001). The adjusted hazard ratio (HR) for first exacerbation was 0.87 (95% CI: 0.74-1.01; P=0.067) among UMEC/VI versus FP/SAL initiators. UMEC/VI initiators had 35% lower adjusted risk of escalation to multiple-inhaler triple therapy (HR 0.65; 95% CI: 0.47-0.89; P=0.008) versus FP/SAL. On-treatment, UMEC/VI initiators had an adjusted 30% reduced risk of a first moderate/severe COPD exacerbation (HR 0.70; 95% CI: 0.54-0.90; P=0.006). Conclusion: Patients with COPD initiating UMEC/VI had higher adherence and longer time before escalation to multiple-inhaler triple therapy than FP/SAL initiators.

Real-life effectiveness of indacaterol-glycopyrronium after switching from tiotropium or salmeterol/fluticasone therapy in patients with symptomatic COPD: the POWER study.

PURPOSE: In contrast to randomized controlled trials (RCTs), changes in maintenance pharmacotherapy in clinical practice occur without a washout period. The Prospective cohort study for the real-life effectiveness evaluation of glycOpyrronium With indacatERol combination in the management of COPD in Canada (POWER) study evaluated the real-life effectiveness of indacaterol/glycopyrronium (IND/GLY) following a direct switch from a long-acting muscarinic antagonist (LAMA, tiotropium) or long-acting ß2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance treatment (salmeterol/fluticasone [SFC]). METHODS: POWER was a single-cohort, prospective, multicenter, interventional study in which patients with moderate-to-severe COPD, who remained symptomatic on their current treatment of once-daily (od) tiotropium 18 µg or twice-daily (bid) SFC (any dose), were switched to treatment with open-label IND/GLY 110/50 µg od for 16 weeks. Effectiveness end points were change from baseline in trough FEV1, transition dyspnea index (TDI) total scores, and COPD assessment test (CAT) scores at 16 weeks. RESULTS: Trough FEV1 improved by 175 mL at Week 16 in patients who switched to IND/GLY. The change was 176 mL (95% CI: 135-217) when switched from tiotropium and 172 mL (95% CI: 85-258) when switched from SFC fixed-dose combination (FDC). At Week 16, significant improvements were observed in the mean TDI total scores (Δ=2.5) and CAT scores (Δ=-6.5) after the switch to IND/GLY treatment (both P<0.0001). Additionally, IND/GLY was well tolerated in patients with moderate-to-severe COPD, and no safety signal was observed. CONCLUSION: In clinical practice settings, a direct switch from previous treatment with either tiotropium or SFC to IND/GLY was safe and provided superior clinically significant improvements in lung function and patient-related outcomes in patients with moderate-to-severe COPD. CLINICAL TRIAL REGISTRATION: NCT02202616.

Preventing Clinically Important Deterioration of COPD with Addition of Umeclidinium to Inhaled Corticosteroid/Long-Acting ß2-Agonist Therapy: An Integrated Post Hoc Analysis.

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 ß2-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.

The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study.

Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting ß-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 µg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 µg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 µg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.

LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.

BACKGROUND: The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. METHODS: In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 µg once daily or SFC 50/500 µg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26. RESULTS: Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%). CONCLUSION: These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.