Early genetic testing in pediatric epilepsy: Diagnostic and cost implications.

The identification of numerous genetically based epilepsies has resulted in the widespread use of genetic testing to inform epilepsy etiology. Our study aims to investigate whether a difference exists in the diagnostic evaluation and healthcare-related cost expenditures of pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis through multigene epilepsy panel (MEP) testing and comparing those who underwent early (EGT) versus late genetic testing (LGT). Testing was defined as early (less than 1 year), or late (more than 1 year), following clinical epilepsy diagnosis. A retrospective chart review of pediatric individuals (1-17 years) with epilepsy of unknown etiology who underwent multigene epilepsy panel (MEP) testing identified 28 of 226 (12%) individuals with a pathogenic epilepsy variant [EGT n = 8 (29%); LGT n = 20 (71%)]. The average time from clinical epilepsy diagnosis to genetic diagnosis was 0.25 years (EGT), compared with 7.1 years (LGT). The EGT cohort underwent fewer metabolic tests [EGT n = 0 (0%); LGT n = 16 (80%) (P < 0.01)] and invasive procedures [EGT n = 0 (0%); LGT n = 5 (25%) (P = 0.06)]. Clinical management changes implemented due to genetic diagnosis occurred in 10 (36%) patients [EGT n = 2 (25%); LGT n = 8 (40%) (P = 0.76)]. Early genetic testing with a MEP in pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis is associated with fewer non-diagnostic tests and invasive procedures and reduced estimated overall healthcare-related costs. PLAIN LANGUAGE SUMMARY: This study aims to investigate whether a difference exists in the diagnostic evaluation and cost expenditures of pediatric patients (1-17 years) with epilepsy of unknown cause who are ultimately diagnosed with a genetic cause of epilepsy through multigene epilepsy panel testing and comparing those who underwent early testing (less than 1 year) versus late testing (more than 1 year) after clinical epilepsy diagnosis. Of the 28 of 226 individuals with a confirmed genetic cause of epilepsy on multigene epilepsy panel testing, performing early testing was associated with fewer non-diagnostic tests, fewer invasive procedures and reduced estimated overall healthcare-related costs.

Implementing comprehensive pharmacogenomics in a community hospital-associated primary care setting.

BACKGROUND: Pharmacogenomics (PGx) is an emerging field. Many drug-gene interactions are known but not yet routinely addressed in clinical practice. Therefore, there is a significant gap in care, necessitating development of implementation strategies. OBJECTIVE: The objective of the study was to assess the impact of implementing a PGx practice model which incorporates comprehensive pharmacogenomic risk evaluation, testing and medication optimization administered by 7 PGx-certified ambulatory care pharmacists embedded across 30 primary care clinic sites. METHODS: Pharmacogenomic services were implemented in 30 primary care clinics within the Cincinnati, Ohio area. Patients are identified for pharmacogenomic testing using a clinical decision support tool (CDST) that is fully integrated in the electronic medical record (EMR) or by provider designation (e.g., psychotropic drug failure). Pharmacogenomic testing is performed via buccal swab using standardized clinic processes. Discrete data results are returned directly into the EMR/CDST for review by PGx-certified ambulatory care pharmacists. Recommendations and prescriptive changes are then discussed and implemented as a collaborative effort between pharmacist, primary care provider, specialists, and patient. RESULTS: A total of 422 unique interactions were assessed by the embedded ambulatory care PGx pharmacists (N = 7) during this interim analysis. About half (213) were pharmacogenomic interactions, and of these, 124 were actionable. When an intervention was actionable, 82% of the time a change in medication was recommended. The underlying reasons for recommending therapy alterations were most commonly ineffective therapy (43%), adverse drug reaction prevented (34%), or adverse drug reaction observed (13%). CONCLUSION: Variations in drug metabolism, response, and tolerability can negatively impact patient outcomes across many disease states and treatment specialties. Incorporation of pharmacogenomic testing with accessible clinical decision support into the team-based care model allows for a truly comprehensive review and optimization of medications. Our initial analysis suggests that comprehensive PGx testing should be considered to enhance medication safety and efficacy in at-risk patients.

Validation of Pharmacogenomic Interaction Probability (PIP) Scores in Predicting Drug-Gene, Drug-Drug-Gene, and Drug-Gene-Gene Interaction Risks in a Large Patient Population.

Utilizing pharmacogenomic (PGx) testing and integrating evidence-based guidance in drug therapy enables an improved treatment response and decreases the occurrence of adverse drug events. We conducted a retrospective analysis to validate the YouScript® PGx interaction probability (PIP) algorithm, which predicts patients for whom PGx testing would identify one or more evidence-based, actionable drug-gene, drug-drug-gene, or drug-gene-gene interactions (EADGIs). PIP scores generated for 36,511 patients were assessed according to the results of PGx multigene panel testing. PIP scores versus the proportion of patients in whom at least one EADGI was found were 22.4% vs. 22.4% (p = 1.000), 23.5% vs. 23.4% (p = 0.6895), 30.9% vs. 29.4% (p = 0.0667), and 27.3% vs. 26.4% (p = 0.3583) for patients tested with a minimum of 3-, 5-, 14-, and 25-gene panels, respectively. These data suggest a striking concordance between the PIP scores and the EAGDIs found by gene panel testing. The ability to identify patients most likely to benefit from PGx testing has the potential to reduce health care costs, enable patient access to personalized medicine, and ultimately improve drug efficacy and safety.

Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer.

Importance: In 2020, some health insurance plans updated their medical policy to cover germline genetic testing for all patients diagnosed with colorectal cancer (CRC). Guidelines for universal tumor screening via microsatellite instability and/or immunohistochemistry (MSI/IHC) for mismatch repair protein expression for patients with CRC have been in place since 2009. Objectives: To examine whether uptake of MSI/IHC screening and germline genetic testing in patients with CRC has improved under these policies and to identify actionable findings and management implications for patients referred for germline genetic testing. Design, Setting, and Participants: The multicenter, retrospective cohort study comprised 2 analyses of patients 18 years or older who were diagnosed with CRC between January 1, 2017, and December 31, 2020. The first analysis used an insurance claims data set to examine use of MSI/IHC screening and germline genetic testing for patients diagnosed with CRC between 2017 and 2020 and treated with systemic therapy. The second comprised patients with CRC who had germline genetic testing performed in 2020 that was billed under a universal testing policy. Main Outcomes and Measures: Patient demographic characteristics, clinical information, and use of MSI/IHC screening and germline genetic testing were analyzed. Results: For 9066 patients with newly diagnosed CRC (mean [SD] age, 64.2 [12.7] years; 4964 [54.8%] male), administrative claims data indicated that MSI/IHC was performed in 6645 eligible patients (73.3%) during the study period, with 2288 (25.2%) not receiving MSI/IHC despite being eligible for coverage. Analysis of a second cohort of 55 595 patients with CRC diagnosed in 2020 and covered by insurance found that only 1675 (3.0%) received germline genetic testing. In a subset of patients for whom germline genetic testing results were available, 1 in 6 patients had pathogenic or likely pathogenic variants, with most of these patients having variants with established clinical actionability. Conclusions and Relevance: This nationwide cohort study found suboptimal rates of MSI/IHC screening and germline genetic testing uptake, resulting in clinically actionable genetic data being unavailable to patients diagnosed with CRC, despite universal eligibility. Effective strategies are required to address barriers to implementation of evidence-based universal testing policies that support precision treatment and optimal care management for patients with CRC.

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Relationship of COPD Exacerbation Severity and Frequency on Risks for Future Events and Economic Burden in the Medicare Fee-For-Service Population.

Purpose: To quantify the effects of moderate and/or severe chronic obstructive pulmonary disease (COPD) exacerbations on future exacerbations and healthcare costs in Medicare Fee-For-Service beneficiaries. Patients and Methods: A retrospective cohort study of patients ≥40 years of age, with continuous enrollment from 2015 to 2018, with an index COPD diagnosis defined as first hospitalization, emergency department visit, or first of two outpatient visits (≥30 days apart) in 2015 with a claim for chronic bronchitis, emphysema, or chronic airway obstruction. Patients were stratified by baseline exacerbation categories in year one (YR1) and subsequently evaluated in YR2 and YR3: (A) none; (B) 1 moderate; (C) ≥2 moderate; (D) 1 severe; and (E) ≥2, one being severe. Moderate exacerbations were defined as COPD-related outpatient/ED visits with a corticosteroid/antibiotic claim within ±7 days of the visit and severe exacerbations as hospitalizations with a primary COPD diagnosis. Total all-cause costs for Categories B-E were compared to reference Category A using generalized linear models and inflation adjusted to 2019 dollars. Results: A total of 1,492,108 patients met study criteria with a mean (±SD) age of 70.9±10.9. In YR1, nearly 40% of patients experienced ≥1 moderate and/or severe exacerbations. Patients having multiple exacerbations, regardless of severity were 2-4 times more likely to experience an exacerbation during YR2 and YR3. Adjusted costs ranged between $24,000 and $26,600 for all categories for YR2 and YR3. Adjusted YR2 costs for Category D and E were $1421 and $1548 higher than those without an exacerbation (Category A YR2 $25,084, YR3 $24,282; p<0.0001). The respective YR3 adjusted costs were $2062 and $2117 higher than those without an exacerbation (Category A; p<0.0001), representing an increase of 6-8% and 8-9% for YR2 and YR3. Conclusion: Medicare patients with recent moderate or severe exacerbations, or at least two exacerbations per year are at significant risk for future exacerbations and incur higher all-cause costs.

Unmanaged Pharmacogenomic and Drug Interaction Risk Associations with Hospital Length of Stay among Medicare Advantage Members with COVID-19: A Retrospective Cohort Study.

Unmanaged pharmacogenomic and drug interaction risk can lengthen hospitalization and may have influenced the severe health outcomes seen in some COVID-19 patients. To determine if unmanaged pharmacogenomic and drug interaction risks were associated with longer lengths of stay (LOS) among patients hospitalized with COVID-19, we retrospectively reviewed medical and pharmacy claims from 6025 Medicare Advantage members hospitalized with COVID-19. Patients with a moderate or high pharmacogenetic interaction probability (PIP), which indicates the likelihood that testing would identify one or more clinically actionable gene-drug or gene-drug-drug interactions, were hospitalized for 9% (CI: 4-15%; p < 0.001) and 16% longer (CI: 8-24%; p < 0.001), respectively, compared to those with low PIP. Risk adjustment factor (RAF) score, a commonly used measure of disease burden, was not associated with LOS. High PIP was significantly associated with 12-22% longer LOS compared to low PIP in patients with hypertension, hyperlipidemia, diabetes, or chronic obstructive pulmonary disease (COPD). A greater drug-drug interaction risk was associated with 10% longer LOS among patients with two or three chronic conditions. Thus, unmanaged pharmacogenomic risk was associated with longer LOS in these patients and managing this risk has the potential to reduce LOS in severely ill patients, especially those with chronic conditions.

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.

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.

Incremental Costs Associated with Length of Hospitalization Due to Viral Pneumonia: Impact of Intensive Care and Economic Implications of Reducing the Length of Stay in the Era of COVID-19.

BACKGROUND: Emerging trial data for treatment of COVID-19 suggest that in addition to improved clinical outcomes, these treatments reduce length of hospital stay (LOS). However, the economic value of a shortened LOS is unclear. OBJECTIVE: To estimate incremental costs per day of hospitalization for a patient with influenza or viral pneumonia, as a proxy for COVID-19; ICU costs associated with invasive mechanical ventilation (iMV) were also determined. METHODS: Retrospective analysis of claims-based data was conducted using the IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Care and the Medicare Fee-for-Service claims databases for hospitalizations due to influenza/viral pneumonia between January 2018 and June 2019. Cases were stratified as uncomplicated hospitalizations or with ICU. Ordinary least squares regression, excluding LOS or costs exceeding the 99th percentile (base case), was used to estimate incremental costs per day; a sensitivity analysis included all qualified hospitalizations. Additional sensitivity analyses used weighting methodology. RESULTS: Among 6055 and 118,419 hospitalizations in the commercially insured and Medicare databases, respectively, 5958 and 116,552 hospitalizations, respectively, represented the base case. Estimated incremental base case costs per additional inpatient day were $2158 and $3900 in the commercial population for uncomplicated hospitalizations and hospitalizations with ICU, respectively, and $475 and $668, respectively in the Medicare population. Estimated incremental base case costs per additional ICU day were $5254 and $608 for Commercial and Medicare populations, respectively. Higher absolute costs were estimated in the sensitivity analysis on all qualified hospitalizations; the weighted sensitivity analyses generally showed that estimates were stable. Use of iMV increased costs by $35,482 and $13,101 in the commercial and Medicare populations, respectively. CONCLUSION: The incremental daily cost of a hospitalization is substantial for US patients with commercial insurance and for Medicare patients. These findings may help quantify the economic value of COVID-19 treatments that reduce LOS.

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.

Evaluation of Medication Adherence and Rescue Medication Use in Non-Exacerbating Patients with COPD Receiving Umeclidinium/Vilanterol or Budesonide/Formoterol as Initial Maintenance Therapy.

Background: Adherence to inhaled maintenance therapy is critical to managing chronic obstructive pulmonary disease (COPD), while increasing rescue medication usage may indicate worsening symptoms. This study evaluated adherence and rescue medication use in patients with COPD without a history of exacerbation who initiated combination therapy with budesonide/formoterol (B/F) or umeclidinium/vilanterol (UMEC/VI). Methods: Retrospective observational study of commercially insured and Medicare Advantage with Part D enrollees who initiated UMEC/VI or B/F between January 1, 2014 and December 31, 2017 (earliest fill defined as index date). Eligibility criteria included age ≥40 years, 12 months continuous enrollment pre- and post-index, ≥1 pre-index COPD diagnosis, no pre-index asthma diagnosis, COPD-related exacerbations, or medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists. Inverse probability of treatment weighting (IPTW) was used to balance treatment groups on potential confounders. Medication adherence (primary endpoint) was evaluated by the proportion of days covered (PDC). Rescue medication use (secondary endpoint) was standardized to canister equivalents (1 metered dose inhaler [200 puffs] or ~100 nebulized doses of short-acting ß2-agonist- and/or short-acting muscarinic agonist-containing medication). Results: After IPTW, covariates were balanced between cohorts (UMEC/VI: N=4082; B/F: N=9529). UMEC/VI initiators had a significantly greater mean PDC (UMEC/VI: 0.47 [0.33]; B/F: 0.38 [0.30]; P<0.001) and significantly higher rates of adherence (PDC≥0.80) than B/F initiators (UMEC/VI: n=1004 [25%], B/F: n=1391 [15%]; relative risk: 1.68, 95% CI: 1.57, 1.81; P<0.001). In the year following initiation, UMEC/VI initiators filled significantly fewer rescue medication canister equivalents than B/F initiators (predicted mean [95% CI]: 1.78 [1.69, 1.88] vs 2.15 [2.08, 2.23]; mean difference [95% CI]: -0.37 [-0.50, -0.24]; P<0.001), corresponding to 17% less (estimated) rescue medication use (incidence rate ratio [95% CI]: 0.83 [0.78, 0.88]). Conclusion: Among non-exacerbating patients with COPD initiating dual therapy, UMEC/VI demonstrated improved adherence and reduced rescue medication use compared with B/F.

Health care resource utilization among patients with T2D and cardiovascular-, heart failure-, or renal-related hospitalizations.

OBJECTIVES: In patients with type 2 diabetes (T2D), comorbidity-related hospitalizations can have significant impact on longitudinal care. This study aimed to estimate incremental all-cause health care resource utilization (HCRU) and costs between patients with T2D who experienced cardiovascular (CV)-, heart failure (HF)-, or renal-related hospitalizations vs those who did not. STUDY DESIGN: This was a retrospective cohort study using data from a large national health plan. METHODS: Patients with T2D aged 18 to 90 years with CV, HF, or renal hospitalizations were identified from the Humana claims database from October 1, 2009, to September 30, 2015, and separated into CV, HF, and renal cohorts. Patients had 12 months of continuous enrollment prior to the date of first hospitalization (index) and were followed for up to 12 months. Per-patient per-month (PPPM) all-cause HCRU and costs for hospitalized patients were compared with those of no-CV, no-HF, and no-renal cohorts. Differences in baseline characteristics between cohorts were controlled for using generalized linear models. RESULTS: A total of 221,229, 68,126, and 120,105 patients were included in the CV, HF, and renal cohorts, respectively; these patients were older and had higher Deyo-Charlson Comorbidity Index scores than patients in the no-CV, no-HF, and no-renal cohorts. Adjusted for baseline covariates, they had higher mean PPPM inpatient stays, outpatient visits, emergency department visits, and total health care costs. CONCLUSIONS: Among patients with T2D, concurrent CV, HF, or renal events present significant disease burden leading to poor quality of life. This information can be used to guide disease management strategies and interventions aimed at reducing comorbidity-related hospitalizations and health care costs, thus providing improved quality of life for these patients.

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.

Spirometry evaluation to assess performance of a claims-based predictive model identifying patients with undiagnosed COPD.

BACKGROUND: A claims-based model to predict patients likely to have undiagnosed COPD was developed by Moretz et al in 2015. This study aims to assess the performance of the aforementioned model using prospectively collected spirometry data. METHODS: A study population aged 40-89 years enrolled in a Medicare Advantage plan with prescription drug coverage or commercial health plan and without a claim for COPD diagnosis was identified from April 1, 2012 to March 31, 2016 in the Humana claims database. This population was stratified into subjects likely or unlikely to have undiagnosed COPD using the claims-based predictive model. Subjects were randomly selected for spirometry evaluation of FEV1 and FVC. The predictive model was validated using airflow limitation ratio (FEV1/FVC <0.70). RESULTS: A total of 218 subjects classified by the predictive model as likely and 331 not likely to have undiagnosed COPD completed spirometry evaluation. Those predicted to have undiagnosed COPD had a higher mean age (70.2 vs 67.9 years, P=0.0012) and a lower mean FEV1/FVC ratio (0.724 vs 0.753, P=0.0002) compared to those predicted not to have undiagnosed COPD. Performance metrics for the predictive model were: area under the curve =0.61, sensitivity =52.5%, specificity =64.6%, positive predictive value =33.5%, and negative predictive value =80.1%. CONCLUSION: The claims-based predictive model identifies those not at risk of having COPD eight out of ten times, and those who are likely to have COPD one out of three times.

Development and validation of a predictive model to identify patients at risk of severe COPD exacerbations using administrative claims data.

Background: Patients with COPD often experience severe exacerbations involving hospitalization, which accelerate lung function decline and reduce quality of life. This study aimed to develop and validate a predictive model to identify patients at risk of developing severe COPD exacerbations using administrative claims data, to facilitate appropriate disease management programs. Methods: A predictive model was developed using a retrospective cohort of COPD patients aged 55-89 years identified between July 1, 2010 and June 30, 2013 using Humana's claims data. The baseline period was 12 months postdiagnosis, and the prediction period covered months 12-24. Patients with and without severe exacerbations in the prediction period were compared to identify characteristics associated with severe COPD exacerbations. Models were developed using stepwise logistic regression, and a final model was chosen to optimize sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV). Results: Of 45,722 patients, 5,317 had severe exacerbations in the prediction period. Patients with severe exacerbations had significantly higher comorbidity burden, use of respiratory medications, and tobacco-cessation counseling compared to those without severe exacerbations in the baseline period. The predictive model included 29 variables that were significantly associated with severe exacerbations. The strongest predictors were prior severe exacerbations and higher Deyo-Charlson comorbidity score (OR 1.50 and 1.47, respectively). The best-performing predictive model had an area under the curve of 0.77. A receiver operating characteristic cutoff of 0.4 was chosen to optimize PPV, and the model had sensitivity of 17%, specificity of 98%, PPV of 48%, and NPV of 90%. Conclusion: This study found that of every two patients identified by the predictive model to be at risk of severe exacerbation, one patient may have a severe exacerbation. Once at-risk patients are identified, appropriate maintenance medication, implementation of disease-management programs, and education may prevent future exacerbations.