Real-world effectiveness of dupilumab versus benralizumab and mepolizumab.

INTRODUCTION: In the United States, this real-world study compared the effectiveness of dupilumab, benralizumab, andmepolizumab in reducing exacerbations and systemic corticosteroid (SCS) prescriptions among patients with asthma. METHODS: Patients (12 years old) who initiated dupilumab, benralizumab, or mepolizumab (index) between November 2018 and September 2020 were identified by using electronic medical record data. Subjects were included if they had greater than or equal to 12 months of data before and after the index date and two or more severe asthma-related exacerbations before the index date. Differences in baseline characteristics were addressed by using inverse probability treatment weighting (IPTW). Pairwisecomparisons between dupilumab and benralizumab, or mepolizumab were conducted by using negative binomial regression, adjusting for baseline rates and unbalance characteristics (greater than or equal to 10% standardized differences) after IPTW. RESULTS: Overall, a total of 1737 subjects met all criteria: 825 dupilumab, 461 benralizumab, and 451 mepolizumab initiators.In the postindex period, dupilumab was associated with a 24% and 28% significant reduction in the risk of severe asthmaexacerbations versus benralizumab (incidence rate ratio [IRR] 0.76 [95% confidence interval {CI}, 0.67-0.86)] and mepolizumab(IRR 0.72 [95% CI, 0.63-0.82]), respectively. In addition, dupilumab treatment significantly reduced SCS prescriptionsby 16% and 25% versus benralizumab and mepolizumab, respectively (p < 0.05). CONCLUSION: This study represents one of the largest real-world comparisons of biologics (dupilumab, benralizumab, and mepolizumab) for asthma in the United States to date. This analysis shows that the use of dupilumab was associated with a significantly greater reduction in both severe asthma exacerbations and SCS prescriptions compared with benralizumab and mepolizumab.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Hereditary factor X deficiency in America survey: impact on quality of life and burden of disease in patients and caregivers.

Hereditary factor X deficiency (HFXD) is a rare bleeding disorder causing delayed haemostasis and potentially life-threatening bleeds. Patient/caregiver burden and diagnosis path have not been well characterized. THE AIM OF THIS STUDY WAS TO: describe the diagnosis path, disease burden, and HFXD impact on quality of life (QoL) in patients and caregivers.This was a prospective, cross-sectional, web-based survey of patients with HFXD and caregivers addressing the patient/caregiver experience, QoL, humanistic and unmet needs.Thirty patients and 38 caregivers completed the survey with mean ages 24.7 and 44.6 years, respectively. Mean age at diagnosis was 4.1 years. The diagnostic process was somewhat/very difficult for 23% of patients and 26% of caregivers. Approximately half (53%) received single factor replacement (SFR) as prophylaxis or on-demand. Most patients (71%) reported regular prophylaxis treatment. Over one-fourth (27%) reported treatment with fresh frozen plasma. Bleeding episodes were less common in patients using SFR versus non-SFR: three bleeds or fewer were reported by 92% SFR and 75% non-SFR patients. HFXD patients reported low well being in work/school/social activities with mean HFXD-adapted Hemophilia Well being Index. Patient symptoms negatively impacted caregiver burden with a mean HFXD-adapted Hemophilia Caregiver Index (±SD) of 15.9 (4.6), but also unexpectedly had a positive impact on self-worth and inner strength.To our knowledge, this is the first study to assess patient and caregiver burden of HFXD and impact on QoL. Improvements in symptom recognition, prompt diagnosis, and adherence to expert recommendations for treatment could improve QoL and decrease burden on HFXD patients and caregivers.

Real-world effectiveness of dupilumab in patients with asthma: Findings from the US ADVANTAGE study.

BACKGROUND: Dupilumab is approved as an add-on maintenance therapy for patients (≥6 years) with moderate-to-severe asthma. Better understanding of real-world effectiveness is needed. OBJECTIVE: To characterize the real-world effectiveness of dupilumab in asthma management. METHODS: This retrospective study included patients (≥12 years of age) diagnosed with asthma, initiating dupilumab between November 2018 and September 2020. The study used a US electronic medical record database (TriNetX Dataworks, Cambridge, Massachusetts). Asthma exacerbation rates before and after the initiation of dupilumab were analyzed using generalized estimating equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses were conducted based on previous exacerbation data, eosinophil levels, history of atopic dermatitis or chronic rhinosinusitis with nasal polyps, previous use of biologics, and presence of SARS-CoV-2 (COVID-19). RESULTS: A total of 2400 patients initiating dupilumab met all study criteria. After initiation of dupilumab, risk of asthma exacerbation was reduced by 44% (IRR, 0.56; 95% CI, 0.47-0.57; P = <0.0001) and systemic corticosteroid prescriptions by 48% (IRR, 0.52; 95% CI, 0.48, 0.56; P = <0.0001) compared with those before initiation of dupilumab. Adjustment for COVID-19 showed a greater reduction in asthma exacerbations (IRR, 0.50; 95% CI, 0.45-0.55; P = <0.0001). CONCLUSION: Current real-world efficacy evidence indicates that dupilumab reduces asthma exacerbations and total systemic corticosteroid prescriptions in clinical practice. The effectiveness of dupilumab was observed independent of exacerbation history, eosinophil levels, or COVID-19 impact.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control.

OBJECTIVE: To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma. DATA SOURCES: PubMed and EMBASE databases were used for a structured literature analysis. STUDY SELECTIONS: Full-text, English-language articles that reported findings from qualitative studies conducted in adults, focusing on patient descriptors of asthma symptoms, impacts, or severity, were included. Pediatric studies, studies conducted in patients without asthma, and studies that did not contain qualitative data were excluded. RESULTS: ACT items reflected all domains of asthma impairment described in the NHLBI guidelines, except pulmonary function. Following the literature review, 28 full-text publications were identified that included patient descriptors that could be mapped to ACT items. For example, per ACT Item 1, patients described having trouble at work, school, and completing household chores; and, per ACT Item 2, patients used the phrase "short of breath" to describe asthma-associated symptoms. CONCLUSION: ACT item content corresponded well with the NHLBI guideline definitions of the impairment domain of asthma control (focused on asthma symptoms and impact), and we identified numerous examples in the literature indicating that ACT concepts and item content mirror the language patients use when discussing asthma symptoms and impact, and their degree of asthma control. This provides further evidence to support content validity of the ACT as a measure of asthma control.

Continuity of Care Assessment Within a Vertically Integrated Care Management Organization Before and After COPD-Related Exacerbations.

BACKGROUND: There is currently little research describing patient experience and continuity of care immediately prior, during, and following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This analysis examined clinical characteristics, chronic obstructive pulmonary disease (COPD)­related medication patterns and outpatient visits before and after an AECOPD. METHODS: This retrospective analysis used electronic health records, medical claims, and pharmacy dispensing data for patients within the Kaiser Permanente Northwest Health System. Patients with ≥1 AECOPD between January 1, 2015 and December 31, 2017 were identified. The most recent AECOPD was considered the index date. An AECOPD was defined as an inpatient hospitalization with a primary diagnosis of COPD, or respiratory failure with a secondary diagnosis of COPD, or an outpatient visit with a primary diagnosis of COPD and dispensing of respiratory-related antibiotics and/or oral corticosteroids ±5 days of the visit. Eligible patients were: ≥40 years old; ≥2 encounters within 12 months of each other or ≥1 hospitalization with primary or secondary COPD diagnosis, chronic bronchitis, or emphysema prior to index; and continuously enrolled ±90 days relative to index. COPD-related inhaled maintenance medication, rescue inhalers, oral corticosteroid use, and ambulatory visits were assessed 90-days pre- and post-index. RESULTS: There were 2829 patients included (mean [standard deviation] age: 69.0 [10.5] years) who had an AECOPD (7% severe; 93% moderate). The percentage of patients on inhaled maintenance therapy increased from 60.6% pre-AECOPD to 68.8% post-AECOPD and increased from 60.0% to 87.4% among patients who experienced a severe AECOPD. COPD-related ambulatory visits increased more than four-fold for primary care and more than doubled for pulmonologist visits in the post-AECOPD period. CONCLUSION: The low proportion of patients observed with changes to controller and rescue medication (particularly following a moderate AECOPD), yet higher utilization of COPD-related ambulatory visits before and after an AECOPD suggests that there is opportunity to improve pharmacotherapy management.

Pilot Study of a Patient Experience with an ELLIPTA Inhaler Electronic Medication Monitor and Associated Integrated System: A Prospective Observational Study Using the COPD Patient-Powered Research Network.

BACKGROUND: Electronic medication monitors (EMMs) are associated with decreased rescue inhaler use, symptom burden, and increased medication adherence in asthma. However, the use of EMMs in people with chronic obstructive pulmonary disease (COPD) using the ELLIPTA dry powder inhaler has not been studied. METHODS: This was an open-label, single-arm, prospective observational study of EMMs and associated application (app) use over 12 weeks and up to 24 weeks (April-October 2019) in people with self-reported COPD aged ≥40 years enrolled in the COPD Patient-Powered Research Network, using an ELLIPTA inhaler. The primary outcome was daily active use of the app over 12 weeks. Treatment adherence, rescue inhaler use, and participant satisfaction were assessed over the same period. RESULTS: Among the 122 participants, mean (standard deviation [SD]) proportion of days participants opened the app was 59.5% (31.4), 51.1% (33.5) and 41.3% (34.2) for Days 1-30, 31-60 and 61-90, respectively. Mean (SD) adherence to maintenance medication remained stable: 80.2% (22.7) and 79.9% (26.7) for Days 1-30 and 61-90, respectively. In participants using a rescue inhaler and EMM, mean (SD) rescue-free days increased from 18.5 (10.0; Days 1-30, n=51) to 21.4 (9.6; Days 61-90, n=48). Participants reported high levels of confidence in using the EMM, valued app reminders highly and reported high system satisfaction (mean [SD] scale: 1=low, 5=high; 4.6 [1.1], 4.3 [1.1] and 4.1 [1.1], respectively). CONCLUSIONS: Use of an ELLIPTA EMM with frequent app engagement, high participant satisfaction and decreased rescue medication use may aid COPD management.

Development and validation of a drug adherence index for COPD.

BACKGROUND: Inhaled medications are the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Despite their importance, adherence to these medications is low. Low adherence is linked to increased exacerbation rates, mortality rates, health care utilization, and, ultimately, increased costs. A drug adherence index (DAI) is a predictive modeling tool that identifies patients most likely to change adherence status so that they can be targeted for support programs. Optum has previously developed DAI tools for diabetes, hypertension, and high cholesterol. In this study, a COPD-specific DAI was developed. This DAI tool could be used to better target medication adherence support in patients with COPD, aiming to increase adherence. OBJECTIVES: To develop a COPD-specific DAI using (a) enrollment, medical, and pharmacy variables and (b) only enrollment and pharmacy variables for potential application to pharmacy benefit managers and pharmacy plans. METHODS: This was a retrospective observational study using health care claims among Medicare Advantage with Part D beneficiaries with COPD in the United States. Potential predictors of adherence were measured during a 1-year baseline period. The adherence outcome was measured during a subsequent 1-year at-risk period. Adherence to long-acting bronchodilators was defined as a proportion of days covered (PDC) ≥80%. Nonadherence was defined as a PDC of <80%. Patients were stratified according to their adherence status at baseline, and logistic regression models were developed separately for each set of patients. Separate models were also developed using enrollment, medical, and pharmacy variables (primary objective) or using enrollment and pharmacy variables only (secondary objective). RESULTS: A total of 61,507 patients met all inclusion and exclusion criteria. For the primary objective, at baseline, 31,142 patients were adherent and 30,365 patients were nonadherent. The final DAI model used to predict future nonadherence included 30 covariates, with 7 predictors from medical claims. The validated model c-statistic was 0.752. The final DAI model used to predict future adherence included 29 covariates; only 4 predictors were from medical claims. The validated model c-statistic was 0.691. Findings were similar for the secondary objective using only enrollment and pharmacy variables. CONCLUSIONS: This DAI was developed and validated specifically to predict future adherence status to long-acting bronchodilator medications among patients with COPD. The DAI models performed better for predicting nonadherence than predicting adherence. Both organizations with medical and pharmacy data and organizations with only pharmacy data could utilize the DAI tool to target patients for adherence programs, as results were similar with and without the use of medical variables. DISCLOSURES: This study was sponsored and funded by GlaxoSmithKline (HO-16-17938). The study sponsor participated in the conception and design of the study, analysis and interpretation of the data, and drafting and critical revision of the report and approved submission of the manuscript. All authors had access to the results of the analyses, reviewed and edited the manuscript, approved the final draft, and were involved in the decision to submit the manuscript for publication. The data contained in the Optum database contain proprietary elements owned by Optum and, therefore, cannot be broadly disclosed or made publicly available at this time. The disclosure of these data to third parties assumes certain data security and privacy protocols are in place and that the third party has executed a license agreement that includes restrictive agreements governing the use of the data. Bengtson, Buikema, and Bankcroft are employees at Optum, and Schilling is a former employee of Optum; their employment was not contingent on this work. Optum was funded by GlaxoSmithKline to conduct the study. Stanford was an employee of GlaxoSmithKline at the time of this study and holds stock in GlaxoSmithKline.

Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs.

OBJECTIVE: This real-world observational study compared medication adherence and persistence among patients with asthma receiving the once-daily inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) versus the twice-daily ICS/LABAs budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL). METHODS: This retrospective cohort study conducted using IQVIATM Health Plan Claims Data included patients with asthma ≥18 years of age initiating ICS/LABA therapy with FF/VI, B/F, or FP/SAL between January 1, 2014 and June 30, 2016 (index date). Patients had ≥12 months and ≥3 months of continuous eligibility pre- and post-index date, respectively. Patients receiving FF/VI were separately matched 1:1 with patients receiving B/F or FP/SAL using propensity score matching (PSM) and multivariable regression to balance baseline covariates between cohorts. The primary endpoint was medication adherence, measured by proportion of days covered (PDC). Secondary endpoints included proportion of patients achieving PDC ≥ 0.5 and PDC ≥ 0.8 and persistence with index medication, measured by time to discontinuation (>45-day gap in therapy). RESULTS: After PSM, 3,764 and 3,339 patients receiving FF/VI were matched with patients receiving B/F or FP/SAL, respectively. Mean PDC was significantly higher for FF/VI versus B/F (0.453 vs 0.345; adjusted p < 0.001) and FP/SAL (0.446 vs 0.341; adjusted p < 0.001). The proportion of patients achieving PDC ≥ 0.5 or PDC ≥ 0.8, and treatment persistence were significantly higher for FF/VI versus B/F and FP/SAL (all p < 0.001). CONCLUSIONS: In this real-world study, patients initiating FF/VI had better adherence and lower risk of discontinuing treatment versus B/F or FP/SAL, suggesting that once-daily ICS/LABA treatment might improve adherence and persistence compared with twice-daily alternatives.

The evaluation of the correct use and ease-of use of the ELLIPTA DPI in children with asthma.

RATIONALE: Asthma studies show many children use inhalers incorrectly even after instruction. For two age groups of children with asthma, we determined the proportions who used the once-daily ELLIPTA dry-powder inhaler (DPI) correctly, and who found it easy to use. METHODS: This was a multicenter, single-arm, stratified, open-label, placebo study (NCT03478657). Children aged 5-7 and 8-11 years were trained in, and required to demonstrate, correct placebo ELLIPTA DPI use at their first clinic visit. The inhaler was used at home once daily for 28 ± 2 days. On returning to the clinic, children were randomized to an age-appropriate, ease-of-use questionnaire that had been developed and validated previously, and which rated the inhaler as "easy" or "hard" to use. Following questionnaire completion, children were then asked to demonstrate correct inhaler use. Correct use and ease-of use were assessed in each age group (co-primary endpoints) and overall (secondary endpoints). RESULTS: Of 222 enrolled children, 221 completed the study. Among children aged 5-7 years, 92% (n = 81/88) demonstrated correct ELLIPTA use on their first attempt, compared with 93% (n = 124/133) aged 8-11 years. Of these children, 98% (5-7 years: n = 79/81; 8-11 years: n = 121/124) rated the inhaler easy to use. Overall, 93% (n = 205/221) demonstrated correct inhaler use on their first attempt, and 98% (n = 200/205) rated it easy to use. CONCLUSION: ELLIPTA DPI was used correctly and easily by most children on their first attempt without additional training.

The Identification and Cost of Acute Chronic Obstructive Pulmonary Disease Exacerbations in a United States Population Healthcare Claims Database.

Almost half of chronic obstructive pulmonary disease (COPD) exacerbations are estimated to be inaccurately reported by patients, inconsistently recorded in medical records, or not measured due to coding errors inherent to administrative claims. This retrospective observational study aimed to develop an algorithm capable of detecting acute COPD exacerbations (AECOPD) in healthcare claims and estimate costs associated with AECOPD over a 12-month period. Commercial and Medicare Advantage healthcare plan members (≥40 years old) with evidence of COPD were identified from US healthcare-claims database. To refine the algorithm detecting AECOPD in claims data, sensitivity and positive-predictive value calculations were performed to compare AECOPD identification in healthcare claims versus medical charts. Analyses were also performed to examine total exacerbation-related costs for events identified with the new claims algorithm plus events missed. The final algorithm had a sensitivity of 84.9%, with a positive-predictive value of 67.5%. Medical records were abstracted for 402 patients. In the overall sample of healthcare claims (n = 243,998), the algorithm detected ≥1 AECOPD event in 61.3% of patients. The mean cost per patient during an AECOPD episode, identified by the final algorithm, was USD 6,760 (n = 301), with an incremental average cost of USD 607 (n = 122) to 'unobserved' episodes (not reported in claims data) among the chart sample. After multivariate modeling, predicted yearly exacerbation costs translated to USD 1.12 billion per 100,000 patients (USD 12,000 per patient), with 35.76 million associated with unobserved exacerbations. While the final algorithm warrants further validation and study, these findings highlight unobserved AECOPD and their economic burden.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

COPD exacerbation costs in the IMPACT study: a within-trial analysis.

OBJECTIVES: Exacerbations account for the greatest proportion of costs associated with chronic obstructive pulmonary disease (COPD). Here we aimed to evaluate, from the US payer perspective, the costs associated with moderate and severe COPD exacerbation events for patients treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared with FF/VI or UMEC/VI. STUDY DESIGN: This post hoc, within-trial economic analysis used data derived from the InforMing the PAthway of COPD Treatment (IMPACT) study (NCT02164513). METHODS: Treatment groups within the IMPACT trial received either triple therapy with FF/UMEC/VI (100/62.5/25 mcg) or dual therapy (FF/VI [100/25 mcg] or UMEC/VI [62.5/25 mcg]). The primary end point for this IMPACT post hoc analysis was cost differences between the treatment arms related to 1-year on-treatment combined moderate and severe COPD exacerbation events. RESULTS: The final study sample for this within-trial analysis consisted of 10,355 patients, 49% of whom experienced an on-treatment moderate or severe exacerbation during the study. The mean 1-year on-treatment cost estimate associated with combined moderate and severe exacerbations was highest with UMEC/VI and lowest with FF/UMEC/VI ($6205 vs $4913, respectively). Mean cost differences were statistically significant for all pairwise comparisons of FF/UMEC/VI with FF/VI or UMEC/VI (-$549 [95% CI, -$565 to -$533] and -$1292 [95% CI, -$1313 to -$1272], respectively; both P <.0001). CONCLUSIONS: Treatment with FF/UMEC/VI compared with FF/VI or UMEC/VI in the US healthcare system resulted in lower exacerbation-related costs for combined moderate/severe exacerbation events, as well as moderate and severe exacerbations separately.

Assessment of the COPD Assessment Test Within U.S. Primary Care.

RATIONALE: Uptake of the COPD Assessment Test (CATTM) is not yet widespread in patients with chronic obstructive pulmonary disease (COPD) within U.S. primary care and its alignment with other assessments has not been evaluated in U.S. clinical practice. OBJECTIVES: To assess the alignment of the CAT with other standard measures of COPD severity and its usability in a U.S. primary care population. METHODS: This was a multicenter, prospective, observational, longitudinal study of patients with COPD and their primary care physicians. Patients with spirometry-confirmed airflow restriction completed a daily electronic diary (eDiary) over 12 weeks; surveys were also administered at baseline and at 6- and 12-week follow-up. MEASUREMENTS AND MAIN RESULTS: In the study population (n=178), statistically significant differences (P<0.05) were found across 4 CAT impact score groups where at all time points patients in the Low Impact CAT score group had superior lung function and physical/mental health status than patients in the Medium, High, and Very High Impact groups. Numerical, though lesser, differences were also found across these latter 3 groups. Furthermore, the average total EXAcerbations of COPD Tool (EXACT®) score was significantly worse in patients in the highest CAT score group over the first 7 days. CONCLUSIONS: COPD severity; respiratory symptoms; frequency, severity, and duration of pulmonary exacerbations; and overall physical and mental health status are linked concurrently and prospectively to CAT impact score categories. The stratification of patients according to CAT impact scores, and application of clinical and functional health status information to these categories, enhances the usability of the CAT in practice settings for COPD management.

Validation and Assessment of the COPD Treatment Ratio as a Predictor of Severe Exacerbations.

BACKGROUND: Population-based risk assessments are needed to identify individuals who may benefit from chronic obstructive pulmonary disease (COPD) management programs for preventing exacerbations. This study compared the validated COPD treatment ratio (CTR) versus other COPD exacerbation predictors: prior exacerbation and rescue and maintenance medication use. METHODS: A retrospective observational study using medical and pharmacy claims data among Medicare Advantage with Part D beneficiaries with COPD (January 2011-August 2016). Unadjusted and adjusted logistic regression models tested the predictive performance (C-statistic) of potential exacerbation predictors for future severe exacerbations. RESULTS: The unadjusted association between exacerbation predictors and severe exacerbation was examined in 60,776 patients: baseline severe exacerbation had the highest C-statistic (0.668), then number of rescue units dispensed (0.651), CTR (0.619), and number of controller units dispensed (0.562). During the at-risk period, baseline CTR was inversely associated with severe exacerbation (odds ratio, <1.0); other predictors were positively associated with a severe exacerbation (odds ratio, >1.0). Adjusting for age, geographic region, chronic oxygen, and nebulizer use, the severe exacerbation odds were 0.90 (95% confidence interval [CI], 0.89-0.91) lower per 0.10 change in CTR (C-statistic, 0.710). The C-statistic was 0.734 when baseline exacerbation was added to the model. CONCLUSIONS: The CTR is an effective tool for identifying patients diagnosed with COPD who are at increased risk of severe exacerbation. Although CTR does not predict future exacerbation as well as prior severe exacerbation history, it has the advantage of being applicable in predicting future exacerbations in patients without an exacerbation history, or in databases limited to pharmacy claims only. In addition, the significant reduction in risk has been observed with incremental increases in the ratio: the ratio can be monitored to assess COPD health improvements over time.

Cost analysis of COPD exacerbations and cardiovascular events in SUMMIT.

OBJECTIVES: The Study to Understand Mortality and Morbidity in COPD (SUMMIT) trial compared the efficacy of once-daily fluticasone furoate/vilanterol (FF/VI) with placebo, FF monotherapy, and VI monotherapy on mortality in patients with moderate chronic obstructive pulmonary disease (COPD) and a history/increased risk of cardiovascular (CV) disease. We conducted a post hoc economic analysis using data from SUMMIT to evaluate the economic benefits of treating these patients with COPD and CV risk. STUDY DESIGN: Patients (aged 40-80 years, with ≥10 pack-years' smoking history and a risk of CV events) were randomized (1:1:1:1) to receive placebo, FF 100 mcg, VI 25 mcg, or FF/VI 100 mcg/25 mcg. METHODS: This was a post hoc economic analysis to assess the rates and associated costs of the composite end point (acute COPD exacerbations and revascularization/CV composite events) in the SUMMIT trial from a US healthcare payer perspective. RESULTS: Overall, 16,485 patients were evaluated; of these, 5246 (31.8%) experienced an on-treatment composite end point event (28.5% experienced a COPD exacerbation, 4.2% experienced a CV event, and 2.0% underwent a revascularization procedure). The mean estimated 1-year on-treatment combined end point cost was highest for placebo and lowest for FF/VI ($4220 vs $3482, respectively). The reductions in cost versus placebo were significant for all active treatments (P <.0001). The likelihood of experiencing an on-treatment combined end point event was lower for patients treated with FF/VI versus placebo (hazard ratio, 0.81; P <.001). CONCLUSIONS: One-year combined end point event costs were significantly lower for all active treatments versus placebo. Clinicians and payers may be able decrease costs by effectively managing patients' COPD in those with CV risk.

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.