Treatment Patterns, Healthcare Utilization and Clinical Outcomes of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting ß2-Agonist/Long-Acting Muscarinic Antagonist Dual Therapy in Primary Care in England.

Purpose: Selection of treatments for patients with chronic obstructive pulmonary disease (COPD) may impact clinical outcomes, healthcare resource use (HCRU) and direct healthcare costs. We aimed to characterize these outcomes along with treatment patterns, for patients with COPD following initiation of single-inhaler long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy in the primary care setting in England. Patients and Methods: This retrospective cohort study used linked primary care electronic medical record data (Clinical Practice Research Datalink-Aurum) and secondary care administrative data (Hospital Episode Statistics) in England to assess outcomes for patients with COPD who had a prescription for one of four single-inhaler LAMA/LABA dual therapies between 1st June 2015-31st December 2018 (indexing period). Outcomes were assessed during a 12-month follow-up period from the index date (date of earliest prescription of a single-inhaler LAMA/LABA within the indexing period). Incident users were those without previous LAMA/LABA dual therapy prescriptions prior to index; this manuscript focuses on a subset of incident users: non-triple therapy users (patients without concomitant inhaled corticosteroid use at index). Results: Of 10,991 incident users included, 9888 (90.0%) were non-triple therapy users, indexed on umeclidinium/vilanterol (n=4805), aclidinium/formoterol (n=2109), indacaterol/glycopyrronium (n=1785) and tiotropium/olodaterol (n=1189). At 3 months post-index, 63.3% of non-triple therapy users remained on a single-inhaler LAMA/LABA, and 22.1% had discontinued inhaled therapy. Most patients (86.9%) required general practitioner consultations in the first 3 months post-index. Inpatient stays were the biggest contributor to healthcare costs. Acute exacerbations of COPD (AECOPDs), adherence, time-to-triple therapy, time-to-first on-treatment moderate-to-severe AECOPD, time-to-index treatment discontinuation, HCRU and healthcare costs were similar across indexed therapies. Conclusion: Patients initiating treatment with single-inhaler LAMA/LABA in primary care in England were unlikely to switch treatments in the first three months following initiation, but some may discontinue respiratory medication. Outcomes were similar across indexed treatments.

Characterization of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting Muscarinic Antagonist/Long-Acting ß2-Agonist Dual Therapy in a Primary Care Setting in England.

Purpose: Treatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-inhaler dual therapies remain unclear. We aimed to describe characteristics, prescribed treatments, healthcare resource use (HCRU) and costs of patients with COPD who initiated single-inhaler long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy in primary care in England. Patients and Methods: Retrospective study using linked data from Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. Patients with COPD with ≥1 single-inhaler LAMA/LABA prescription between June 2015 and December 2018 (index) were included. Demographic and clinical characteristics, prescribed treatments, HCRU and costs were evaluated in the 12 months pre-index. Data are presented for patients not receiving concomitant inhaled corticosteroids at index (non-triple users). Results: Of 10,991 patients initiating LAMA/LABA, 9888 were non-triple users, of whom 21.3% (n=2109) received aclidinium bromide/formoterol, 18.1% (n=1785) received indacaterol/glycopyrronium, 12.0% (n=1189) received tiotropium bromide/olodaterol and 48.6% (n=4805) received umeclidinium/vilanterol. Demographic and clinical characteristics were similar across indexed therapies. LAMA monotherapy was the most frequently prescribed respiratory therapy at 12 (18.4-25.8% of patients) and 3 months (23.9-33.7% of patients) pre-index across indexed therapies; 42.5-59.0% of patients were prescribed no respiratory therapy at these time points. COPD-related HCRU during the 12 months pre-index was similar across indexed therapies (general practitioner consultations: 62.0-68.6% patients; inpatient stays: 19.3-26.1% patients). Pre-index COPD-related costs were similar across indexed therapies, with inpatient stays representing the highest contribution. Mean total direct annual COPD-related costs ranged from £805-£1187. Conclusion: Characteristics of patients newly initiating single-inhaler LAMA/LABA dual therapy were highly consistent across indexed therapies. As half of non-triple users were not receiving respiratory therapy one year prior to LAMA/LABA initiation, there may be an opportunity for early optimization of treatment to relieve clinical burden versus current prescribing patterns in primary care in England.

Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis.

INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting ß2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD. METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible). RESULTS: The NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6). CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.

Comparative Efficacy of Umeclidinium/Vilanterol Versus Other Bronchodilators for the Treatment of Chronic Obstructive Pulmonary Disease: A Network Meta-Analysis.

INTRODUCTION: Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD. METHODS: A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented. RESULTS: The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV1 versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 µg, glycopyrronium 50 µg, glycopyrronium 18 µg, tiotropium 18 µg and salmeterol 50 µg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation. CONCLUSION: UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV1 at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.

Bronchodilators are medicines that open the airways, allowing patients with chronic obstructive pulmonary disease (COPD) to breathe more easily. There are two different types of bronchodilators, namely long-acting muscarinic antagonists (LAMAs) and long-acting ß₂-agonists (LABAs), which can be used on their own or combined (LAMA/LABAs). Only a few clinical trials have compared different LAMA/LABA combinations with each other, so it is unclear which LAMA/LABA combination provides the greatest benefits for patients.In this study, we used network meta-analysis to compare a LAMA/LABA combination medicine called umeclidinium and vilanterol (UMEC/VI) with other LAMAs and LABAs used alone or in combination to treat patients with COPD. Network meta-analysis is a way of comparing two or more medicines by analysing data from many studies. We systematically searched for evidence from clinical trials in adult patients with COPD that were at least 8 weeks long and that compared LAMA/LABA combinations with a LAMA, a LABA, or another LAMA/LABA combination. We analysed data from 49 clinical trials that met these criteria.We found that patients treated with UMEC/VI had better lung function than patients treated with alternative LAMA/LABA combinations or bronchodilators used on their own. Patients treated with UMEC/VI had better quality of life than those receiving some other treatments, but not all. All the medicines we compared had similar side effects.Our results suggest that treating patients with COPD with UMEC/VI might improve their lung function and quality of life more than alternative bronchodilators.