Time-to-first exacerbation, adherence, and medical costs among US patients receiving umeclidinium/vilanterol or tiotropium as initial maintenance therapy for chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs. This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO). METHODS: This retrospective matched cohort study selected patients from Optum's de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing). Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date. Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM). Propensity score matching was used to adjust for potential confounders. RESULTS: Each cohort included 3929 matched patients. Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05). UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs. CONCLUSIONS: These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.

Umeclidinium/Vilanterol Compared with Fluticasone Propionate/Salmeterol, Budesonide/Formoterol, and Tiotropium as Initial Maintenance Therapy in Patients with COPD Who Have High Costs and Comorbidities.

BACKGROUND: Comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased medical costs and risk of exacerbations. This study compared COPD-related medical costs and exacerbations in high-cost, high-comorbidity patients with COPD receiving initial maintenance treatment (IMT) with umeclidinium/vilanterol (UMEC/VI) versus fluticasone propionate/salmeterol (FP/SAL), budesonide/formoterol (B/F), or tiotropium (TIO). METHODS: This retrospective, matched cohort study identified patients from Optum's de-identified Clinformatics Data Mart database who initiated UMEC/VI, FP/SAL, B/F, or TIO between January 1, 2014 and December 31, 2018 (index date defined as date of the first fill). Eligibility criteria included age ≥40 years at index, ≥1 pre-index COPD diagnosis, no pre-index asthma diagnosis, 12 months of continuous insurance coverage pre-index, and high pre-index costs (≥80th percentile of IMT population) and comorbidities (Quan-Charlson comorbidity index ≥3). Propensity score matching was used to control for potential confounders. On-treatment COPD-related medical costs (primary endpoint) and exacerbations were evaluated. RESULTS: Matched cohorts were well balanced on baseline characteristics (UMEC/VI vs FP/SAL: n=1194 each; UMEC/VI vs B/F: n=1441 each; UMEC/VI vs TIO: n=1277 each). Patients receiving UMEC/VI had significantly lower COPD-related medical costs versus FP/SAL (difference: $6587 per patient per year; P=0.048), and numerically lower costs versus B/F and TIO. Patients initiating UMEC/VI had significantly lower risk of COPD-related severe exacerbation versus FP/SAL (hazard ratio [95% CI]: 0.78 [0.62, 0.98]; P=0.032), B/F (0.77 [0.63, 0.95]; P=0.016), and TIO (0.79 [0.64, 0.98]; P=0.028). The rate of COPD-related severe exacerbations was significantly lower with UMEC/VI versus FP/SAL (rate ratio [95% CI]: 0.73 [0.59, 0.91]; P=0.008) and B/F (0.73 [0.59, 0.93]; P=0.012), and numerically lower versus TIO (0.83 [0.68, 1.04]; P=0.080). CONCLUSION: These findings suggest that high-cost, high-comorbidity patients with COPD receiving UMEC/VI compared with FP/SAL, B/F, and TIO as IMT may have lower medical costs and exacerbation risk.

Hospital Admission and Readmission Among US Patients Receiving Umeclidinium/Vilanterol or Tiotropium as Initial Maintenance Therapy for Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are at risk of further readmissions, increased treatment costs, and excess mortality. This study evaluated inpatient admissions and readmissions in patients receiving initial maintenance therapy with umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO). METHODS: This retrospective, matched cohort study identified patients with COPD who initiated maintenance therapy with UMEC/VI or TIO from Optum's de-identified Clinformatics Data Mart database between January 1, 2013, and December 31, 2018 (index date defined as earliest dispensing). Eligibility criteria included: ≥ 1 medical claim for COPD pre-index or on the index date; ≥ 12 months of continuous eligibility pre-index; age ≥ 40 years at index; no pre- or post-index asthma diagnosis; and no pre-index claims for medications containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists. Outcomes included time to first on-treatment COPD-related inpatient admission, rate of on-treatment COPD-related admissions, and rate of all-cause and COPD-related readmissions within 30 and 90 days. Propensity score matching was used to adjust for potential confounders. RESULTS: Matched UMEC/VI and TIO cohorts each included 7997 patients and were balanced on baseline characteristics (mean age 70.9 years; female 47.1-47.6%). Over 12 months, patients initiating UMEC/VI had significantly reduced risk (hazard ratio [95% CI]: 0.87 [0.79, 0.96]; p = 0.006) and rates (rate ratio [95% CI]: 0.80 [0.72, 0.92]; p = 0.008) of COPD-related inpatient admissions compared with TIO. While all-cause readmission rates were similar between treatment cohorts, readmission rates among patients with an initial admission length of stay of 1-3 days were numerically lower for UMEC/VI versus TIO (30-day readmissions: 10.5% vs. 12.4%; 90-day readmissions: 15.5% vs. 19.8%). Similar patterns were observed for COPD-related readmissions. CONCLUSIONS: These findings highlight the real-world benefits of dual therapy with UMEC/VI versus TIO in reducing inpatient admissions and readmissions in patients with COPD, which may translate to lower healthcare costs.

Patients with chronic obstructive pulmonary disease (COPD) who are admitted to the hospital are more likely to be readmitted in the future, have higher healthcare costs, and are more likely to die from their illness. Patients who are readmitted to hospital have even higher treatment costs. Identifying which treatments are best at reducing the number of patients with COPD who are admitted to the hospital may help to improve outcomes and reduce the cost of COPD treatment. We used US healthcare claims data to compare two daily treatments for COPD, umeclidinium/vilanterol and tiotropium. We aimed to find out which treatment was more effective at reducing hospital admissions due to COPD. We also compared how many patients on each treatment were readmitted within 30 or 90 days of their original hospital admission for COPD. We found that patients who started treatment with umeclidinium/vilanterol were less likely to be admitted to the hospital for COPD than patients who started treatment with tiotropium. Similar numbers of patients on each treatment were readmitted to the hospital within 30 or 90 days after they were discharged. However, among patients whose initial hospital stay was short (1­3 days), readmissions within 30 or 90 days were less common with umeclidinium/vilanterol than tiotropium. These findings suggest that umeclidinium/vilanterol may be more effective than tiotropium at reducing the number of patients with COPD who need to be admitted or readmitted to hospital. Starting COPD treatment with umeclidinium/vilanterol may lead to better health outcomes and lower costs than tiotropium.

Symptom Burden and GOLD Classification in Medicare Advantage Patients with COPD Initiating Umeclidinium/Vilanterol or Fluticasone Propionate/Salmeterol Therapy.

Background: Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy. Methods: COPD-diagnosed Medicare Advantage enrollees aged ≥65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores. Results: The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (~40%) than GOLD B (~36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups. Conclusion: After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting ß2-agonist bronchodilators.

Long-acting inhaled bronchodilator medications are recommended as initial maintenance therapy for many patients with COPD. These medications include long-acting muscarinic antagonists (LAMA) and long-acting ß2-agonists (LABA). Combinations of long-acting bronchodilator agents (LAMA/LABA) and inhaled corticosteroids combined with LABA (ICS/LABA) are also used as initial or follow-up therapy in patients with more severe symptoms or at risk of COPD exacerbations. This review summarizes the position of LAMA/LABA combinations in treatment recommendations, and the evidence supporting their placement relative to LAMA monotherapy and ICS/LABA combination therapy, as well as differences within the LAMA/LABA class. Most studies show that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment. There are fewer studies comparing the impact of different medication classes on patients' risk of exacerbations; however, the available evidence suggests that LAMA/LABA treatment and LAMA monotherapy lead to a similar reduction in exacerbation risk, while the effect of LAMA/LABA compared with ICS/LABA remains unclear. The incidence of adverse events is similar with LAMA/LABA and LAMA alone. There is a lower risk of pneumonia with LAMA/LABA compared with ICS/LABA. This evidence supports the use of LAMA/LABA combinations as an initial maintenance therapy option for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations, and as follow-up treatment in patients with uncontrolled symptoms or exacerbations on bronchodilator monotherapy.

Evaluation of rescue medication use and medication adherence receiving umeclidinium/vilanterol versus tiotropium bromide/olodaterol.

Background: This was the first real-world head-to-head study comparing inhaled long-acting muscarinic antagonist/long-acting ß2-agonist fixed-dose combination treatments as maintenance therapy. Methods: Retrospective observational study including commercial, Medicare Advantage with Part D or Part D-only enrollees aged ≥40 years from the Optum Research Database. Patients initiated umeclidinium/vilanterol (UMEC/VI) or tiotropium bromide/olodaterol (TIO/OLO) between June 1, 2015 and November 30, 2016 (index date) with 12 months of pre- and post-index continuous enrollment. Outcomes were modeled following the inverse probability of treatment weighting. The primary endpoint, rescue medication use, was modeled using weighted ordinary least squares regression with bootstrapped variance estimation. Intent-to-treat analysis evaluated non-inferiority and superiority of UMEC/VI to TIO/OLO with thresholds of 0.30 and 0 units, respectively. On-treatment sensitivity analysis evaluated the superiority of UMEC/VI to TIO/OLO for rescue medication use. The secondary endpoint, medication adherence (proportion of days covered [PDC]≥80%), was evaluated using weighted logistic regression. Post hoc weighted Cox proportional hazards regression analysis evaluated escalation to multiple inhaler triple therapy (MITT). Results: The study population included 14,324 patients; 9549 initiated UMEC/VI and 4775 initiated TIO/OLO. During the 12-month post-index period, UMEC/VI initiators used 0.16 fewer adjusted mean units of rescue medication than TIO/OLO initiators (95% CI: -0.28, -0.04), meeting pre-specified non-inferiority (P<0.001) and superiority (P=0.005) criteria; the on-treatment sensitivity analysis for superiority was not statistically significant. Significantly more UMEC/VI than TIO/OLO initiators (28.6% vs 22.7%; P<0.001) achieved a clinically meaningful level (PDC≥80%) of medication adherence. The adjusted risk of escalation to MITT was similar between treatment groups (HR=0.93; 95% CI: 0.81, 1.06; P=0.268). Conclusion: UMEC/VI was superior to TIO/OLO for rescue medication use and UMEC/VI initiators had better medication adherence than TIO/OLO initiators. This study supports findings from a head-to-head trial that demonstrated significant, clinically meaningful improvements in lung function with UMEC/VI versus TIO/OLO.

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.

Assessment of symptom burden and adherence to respiratory medications in individuals self-reporting a diagnosis of COPD within a community pharmacy setting.

OBJECTIVES: Data on symptom burden or medication adherence in patients with chronic obstructive pulmonary disease (COPD) within a community pharmacy setting are limited. This study assessed symptom burden and adherence to respiratory medications in individuals reporting COPD, chronic bronchitis, or emphysema diagnoses visiting community pharmacies. DESIGN: This cross-sectional study enrolled participants visiting 35 community pharmacies in Missouri (October 2016 to April 2017). PARTICIPANTS: Eligible participants (aged 40 years or more with a self-reported history of COPD, prescription for at least 1 COPD maintenance medication during the previous 12 months, and able to complete an English questionnaire) were identified from pharmacy dispensing records. MAIN OUTCOME MEASURES: Participants completed a questionnaire assessing demographics, clinical characteristics, health literacy, COPD Assessment Test (CAT) modified Medical Research Council (mMRC) dyspnea scale scores, and exacerbation history. Recent spirometry data were obtained, if available, from participants' physicians. COPD was classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 criteria. Medication adherence was assessed as proportion of days covered (PDC) from dispensing records. RESULTS: Of 682 participants (mean age 63.0 years; 57% female) with available pharmacy data, 251 (36.8%) had available spirometry data. Most participants had mMRC scores ≥ 2 (60.9%) and CAT scores ≥ 10 (90.2%); 57.2% reported at least 2 moderate or 1 or more severe exacerbations within the previous 12 months. GOLD classifications varied depending on the scale used (mMRC vs. CAT); more participants were classified as group C/D than group A/B, with the highest proportion classified as group D (higher symptom burden and exacerbation risk). Mean PDC was 0.46 ± 0.37; only 28.7% of participants were adherent (PDC ≥ 80%) to at least 1 COPD maintenance medication. CONCLUSION: Individuals self-reporting a COPD diagnosis receiving respiratory medications from community pharmacies in Missouri have a high symptom burden and low medication adherence. Further research should determine reasons for low adherence and ways to reduce COPD symptoms.

Efficacy and safety of the dual bronchodilator combination umeclidinium/vilanterol in COPD by age and airflow limitation severity: A pooled post hoc analysis of seven clinical trials.

BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) and those with more severe airway limitation are perceived to experience reduced efficacy from inhaled bronchodilators, especially those administered in a dry powder inhaler. This study compared the efficacy and safety of a long-acting muscarinic antagonist/long-acting ß2-agonist dry powder combination in elderly patients with COPD and patients with moderate-to-very severe airflow limitation. METHODS: This post hoc pooled analysis of seven randomized studies of ≥12 weeks' duration investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg versus tiotropium (TIO) 18 µg or fluticasone propionate/salmeterol (FP/SAL) 250/50 µg. Change from baseline in trough forced expiratory volume in 1 s (FEV1), a common efficacy measure in all trials, proportion of FEV1 responders (≥100 mL increase from baseline) and safety outcomes were analyzed at Day 28, 56, and 84 in patients classified by age (<65, ≥65, and ≥75 years of age) and severity of baseline airflow limitation (Global initiative for chronic Obstructive Lung Disease [GOLD] stage 2 [moderate] and stage 3/4 [severe/very severe]). A 24-week analysis was also conducted for the UMEC/VI versus TIO comparison. RESULTS: The pooled intent-to-treat population comprised 3821 patients (≥65 years: 44-45%; ≥75 years: 9-10%; GOLD stage 3/4: 50-55%); 2246, 874, and 701 patients received UMEC/VI, TIO, or FP/SAL, respectively. Significant improvements in trough FEV1 at Day 84 were observed with UMEC/VI versus TIO or FP/SAL irrespective of age (all p ≤ 0.029) or GOLD stage (all p < 0.001). The proportion of FEV1 responders at Day 84 was significantly greater with UMEC/VI versus TIO or FP/SAL across all age groups (all p ≤ 0.016) and GOLD stages (all p < 0.001). Safety profiles were similar between treatment groups. CONCLUSION: UMEC/VI consistently demonstrated improved lung function versus TIO and FP/SAL across age and airflow limitation severity subgroups, with no safety concerns, indicating that UMEC/VI provides no loss in efficacy or additional safety concerns for both elderly patients with COPD and patients with severe/very severe airway limitation.

Classification of Patients with COPD on LAMA Monotherapy Using the GOLD Criteria: Analysis of a Claims-Linked Patient Survey Study.

INTRODUCTION: To address the burden of chronic obstructive pulmonary disease (COPD), the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends treatment according to classification of patients by symptom severity and exacerbation risk. This post hoc analysis of a previously reported claims-linked, cross-sectional survey [study 205862 (HO-16-16642)] classified patients with COPD receiving long-acting muscarinic antagonist (LAMA) monotherapy based on the GOLD 2017 categories. METHODS: Eligible patients who were ≥ 40 years of age, with ≥ 2 claims with International Classification of Diseases-10th Revision-Clinical Modification COPD diagnosis codes J40-J44 ≥ 30 days apart during the 12-month baseline period, and ≥ 2 claims for LAMA monotherapy in the 6 months prior to identification, were identified using claims data from the Optum Research Database. Patients completed a survey assessing modified Medical Research Council (mMRC) Dyspnea Scale and COPD Assessment Test (CAT) scores and demographics; clinical characteristics were assessed from claims and survey data, while exacerbation history was assessed from claims data. GOLD symptom severity classifications were low (groups A and C) for patients with low scores on both the CAT and mMRC scales (scores of < 10 and 0-1, respectively), and high (groups B and D) for patients with high scores on either scale (scores of ≥ 10 and 2-4, respectively). RESULTS: Of 433 patients included, 85.5% reported a CAT total score ≥ 10, and 45.5% reported mMRC grades 2-4. During the baseline period, 63.7% of patients had ≤ 1 moderate and 0 severe (hospitalized) exacerbations, and 36.3% had ≥ 1 severe or ≥ 2 moderate exacerbation(s). The proportions of patients with each GOLD classification were: A: 9.0%; B: 54.7%; C: 4.6%; D: 31.6%. CONCLUSIONS: In this population, over 85% of LAMA monotherapy users have symptoms and/or exacerbation risk that may necessitate therapy escalation according to 2017 GOLD guidelines. FUNDING: GlaxoSmithKline [study 205862 (HO-16-16642)].

Predictors of Symptom Burden in Patients with COPD on LAMA Monotherapy: Multivariable Analysis of a Claims-Linked Survey Study.

INTRODUCTION: Many patients with chronic obstructive pulmonary disease (COPD) prescribed long-acting muscarinic antagonist (LAMA) monotherapy remain symptomatic. This multivariable analysis of a previously reported claims-linked, cross-sectional survey assessed symptom burden measured by the COPD assessment test (CAT) in patients treated with LAMA monotherapy. METHODS: Eligible patients aged ≥ 40 years with COPD (≥ 2 International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] diagnosis codes ≥ 30 days apart during the 12-month baseline period) and ≥ 2 claims for LAMA monotherapy in the latter half of the baseline period were identified using claims data from the Optum Research Database. Patients completed a survey and 7-day daily diary; baseline clinical characteristics and resource utilization were assessed from claims data. Association between symptom burden and baseline characteristics was assessed using generalized linear regression modeling with normal distribution and identity link. RESULTS: Overall, 433 patients prescribed LAMA monotherapy with claims-linked survey and diary data were included in the analysis. Most patients (85.5%) had a mean CAT score ≥ 10; 39.0% had scores ≥ 21. Overall, the factors most related to a clinically meaningful increase in CAT score (≥ 2 points) were being diagnosed with COPD for > 5 years and being a current smoker (2.25 points, P = 0.003 and 2.22 points, P = 0.025, respectively). CONCLUSIONS: Results demonstrate that many patients with COPD receiving LAMA monotherapy remain symptomatic, especially those diagnosed > 5 years ago or those who continue to smoke. Use of patient-reported outcomes such as the CAT should be considered part of routine visits for patients with COPD. FUNDING: GlaxoSmithKline (GSK study number 205862 [HO-16-16642]).

Patient-Reported Burden of Illness in a Prevalent COPD Population Treated with Long-Acting Muscarinic Antagonist Monotherapy: A Claims-Linked Patient Survey Study.

INTRODUCTION: Symptom burden in inadequately controlled chronic obstructive pulmonary disease (COPD) considerably impacts quality of life, healthcare resource utilization (HCRU) and associated costs. This claims-linked cross-sectional survey study assessed symptom burden and HCRU among a prevalent population of COPD patients prescribed long-acting muscarinic antagonist (LAMA) monotherapy. METHODS: Patients were identified using claims data from the Optum Research Database. Eligible patients were aged ≥ 40 years with 12 months' continuous enrollment in a US health plan, ≥ 2 medical claims containing COPD diagnosis codes ≥ 30 days apart, and ≥ 2 claims for LAMA monotherapy in the latter half of the 12-month sample identification period. Patients were mailed a cross-sectional survey assessing patient-reported outcomes (PROs) [COPD assessment test (CAT) and modified medical research council dyspnea scale (mMRC)], clinical characteristics, smoking history, and demographics. Patients also completed the Exacerbations of Chronic Pulmonary Disease Tool (EXACT-PRO) daily diary for 7 days. HCRU was assessed from claims data. RESULTS: The study included 433 patients with a self-reported healthcare provider COPD diagnosis, and both claims-based and self-reported LAMA monotherapy treatment (mean age 71.0 years; 59.8% female). Most patients (85.5%) reported a high symptom burden (CAT score ≥ 10), 45.5% had high levels of dyspnea (mMRC grade ≥ 2), and 64.4% reported more severe daily symptoms by the EXACT-PRO. Most patients (71.6%) reported high scores on ≥ 2 PROs. More patients with high symptom burden had COPD-related emergency department visits than those with lower disease burden (27.6% vs 12.7%, P = 0.012). CONCLUSIONS: In conclusion, a large proportion of patients with COPD receiving LAMA monotherapy experienced a high symptom burden and may benefit from therapy escalation. Healthcare professionals can use validated PROs to help them assess symptom burden. FUNDING: GlaxoSmithKline (GSK study number: 205862).

The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk. METHODS: A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1-12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up. RESULTS: 2,200 patients initiating UMEC/VI were included in the study sample. Patients' average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1-5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 ($13,087 vs. $9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6-5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 ($22,766 vs. $16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35-2.23; p < 0.001). CONCLUSIONS: Prompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies.

Systematic literature review and meta-analysis of US-approved LAMA/LABA therapies versus tiotropium in moderate-to-severe COPD.

Dual bronchodilator maintenance therapy may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) versus long-acting muscarinic antagonist (LAMA) monotherapy. The efficacy and safety of US-approved LAMA/long-acting beta-agonist (LABA) combinations versus tiotropium (TIO), a LAMA, were assessed. This systematic review and meta-analysis (GSK: 206938), conducted in MEDLINE, MEDLINE In-process, and EMBASE following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, identified randomized clinical trials (>8 weeks) in moderate-to-severe COPD (per Global Initiative for Chronic Obstructive Lung Disease guidelines), receiving LAMA/LABA or TIO. ENDPOINTS: difference in change from baseline in lung function (forced expiratory volume in 1 s [FEV1]; trough, peak, area under the curve 0-3 h post-dose (AUC0-3), St George's Respiratory Questionnaire (SGRQ) responder rate (≥4-unit improvement), SGRQ total score, and rescue medication use at 12 and 24 weeks. Safety was also assessed. From 5683 citations, the meta-analysis included eight clinical trials. LAMA/LABA significantly improved FEV1 trough (Week 12: 63.0 mL, 95% confidence intervals [CI]: 39.2, 86.8; Week 24: 66.1 mL, 95% CI: 40.0, 92.3), peak (Week 12: 91.5 mL, 95% CI: 70.5, 112.4; Week 24: 92.4 mL, 95% CI: 72.9, 111.9), AUC0-3 (Week 12: 126.8 mL, 95% CI: 108.1, 145.4), SGRQ responder rate at Week 12 (risk ratio: 1.19; 95% CI: 1.09, 1.28), mean SGRQ total score (Week 12: -1.87, 95% CI: -2.72, -1.02; Week 24: -1.05, 95% CI: -2.02, -0.09), and rescue medication use (Week 24: -0.47 puffs/day, 95% CI: -0.64, -0.30) versus TIO (all p ≤ 0.03). The SGRQ responder rate at 24 weeks and adverse events were not significantly different between treatments. US-approved LAMA/LABA therapies improved lung function, SGR,Q and rescue medication use versus TIO, without compromising safety.

Rates of escalation to triple COPD therapy among incident users of LAMA and LAMA/LABA.

BACKGROUND: Improved outcomes have been reported for patients with chronic obstructive pulmonary disease (COPD) receiving combination long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) therapy compared with LAMA monotherapy. However, little is known about the relative characteristics of these patients and their rates of escalation to triple therapy (TT, combining a LAMA, LABA, and inhaled corticosteroid). This study aimed to characterize patients initiating treatment with the LAMA tiotropium (TIO) and the fixed-dose LAMA/LABA combination therapy umeclidinium/vilanterol (UMEC/VI), and to compare rates of escalation to TT between patients receiving these therapies. METHODS: Retrospective study of patients with COPD enrolled in a US health insurance plan during 2013-2015 and newly initiated on TIO or UMEC/VI. Patients were ≥40 years of age at index (date of therapy initiation) with continuous enrollment for 12 months pre-index and ≥30 days post-index. LAMA users were propensity score matched 1:1 to LAMA/LABA users, with TT initiation rates reported by cohort using pharmacy claims. RESULTS: 35,357 patients initiating on TIO and 2407 patients initiating on UMEC/VI were identified. After propensity score matching, the rate of TT initiation was significantly higher in new TIO users (n = 1320) than in new UMEC/VI users (n = 1320) (0.92 vs 0.49 per 100 months of exposure, respectively; p < 0.001). Relative to the UMEC/VI cohort, the TIO cohort had an 87% higher risk of TT initiation (hazard ratio: 1.87; 95% confidence interval: 1.4-2.5; p = 0.001). CONCLUSIONS: Patients receiving UMEC/VI progressed to TT more slowly, and were at lower risk of progressing to TT, than patients receiving TIO.

Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of this pooled analysis was to assess the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD). METHODS: We conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), proportion of FEV1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged < 65, ≥ 65, and ≥ 75 years on Days 28, 56, and 84 (12-week analysis of parallel-group design studies), Days 28, 56, 84, 112, 140, 168, and 169 (24-week analysis of parallel-group design studies), and Days 2, 42, and 84 (12-week analysis of crossover design studies). RESULTS: The UMEC/VI intent-to-treat (ITT) populations comprised 2246, 1296, and 472 patients in the 12-week parallel-group, 24-week parallel-group, and 12-week crossover analysis, respectively (≥ 65 years: 36-44%; ≥ 75 years: 7-11%). The placebo ITT populations comprised 528, 280, and 505 patients, respectively (≥ 65 years: 37-41%; ≥ 75 years: 5-11%). Significant improvements in trough FEV1 and significantly greater proportions of FEV1 responders were seen with UMEC/VI compared with placebo in all analyses regardless of patient age or timepoint considered (p ≤ 0.023), except Day 84 trough FEV1 CFB in the 12-week crossover analysis in patients aged ≥ 75 years (p = 0.064). UMEC/VI safety profile was similar to placebo in all age groups. CONCLUSIONS: In this pooled analysis of RCT data, once-daily UMEC/VI was well tolerated and provided clinically significant lung function benefits compared with placebo in younger and older patients with COPD. FUNDING: GlaxoSmithKline (study 208125).

A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control.

The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.

Clinical Features of Influenza and Acute Respiratory Illness in Older Adults at Least 50 Years of Age in an Outpatient Setting in the Republic of Korea: a Prospective, Observational, Cohort Study.

Two prospective, multi-centre, observational studies (GlaxoSmithKline [GSK] identifier No. 110938 and 112519) were performed over 2 influenza seasons (2007-2008 and 2008-2009) in the Republic of Korea (ROK) with the aim to evaluate the burden of laboratory-confirmed influenza (LCI) in patients ≥ 50 years of age seeking medical attention for acute respiratory illness (ARI). The median participant age was 58 years in the 2007-2008 season and 60 years in the 2008-2009 season. LCI was observed in 101/346 (29.2%) of ARI patients in the 2007-2008 season and in 166/443 (37.5%) of ARI patients in the 2008-2009 season. Compared to patients with non-influenza ARI, those with LCI had higher rates of decreased daily activities (60.4% vs. 32.9% in 2007-2008 and 46.4% vs. 25.8% in 2008-2009), work absenteeism (51.1% vs. 25.6% and 14.4% vs. 7.7%), and longer duration of illness. These results indicated that influenza is an important cause of ARI in adults aged 50 and older causing more severe illness than non-influenza related ARI.

Evidence update: GlaxoSmithKline's inactivated quadrivalent influenza vaccines.

Inactivated trivalent influenza vaccines (IIV3s) are designed to protect against illness caused by two influenza A virus subtypes and one influenza B virus lineage. They may provide inadequate protection due to the co-circulation of viruses from two antigenically distinct influenza B lineages. Incorporating strains from both B lineages as in inactivated quadrivalent influenza vaccines (IIV4s) reduces this risk. We summarize the evidence supporting two IIV4s manufactured by GSK Vaccines. Compared to IIV3s, these two IIV4s demonstrated noninferior immunogenicity against the shared influenza strains and superior immunogenicity for the strain of the additional B lineage, particularly in subjects who were seronegative for that B strain. One IIV4's efficacy in children aged 3-8 years was 55.4% against influenza of any severity and 73.1% against moderate-to-severe influenza. Both IIV4s were well-tolerated with a similar safety profile to IIV3s. These IIV4s are more likely than IIV3s to protect against the added influenza B strain.