Low Meningococcal Vaccination Rates Among Patients With Newly Diagnosed Complement Component Deficiencies in the United States.

Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

Clinical and economic burden of chronic rhinosinusitis with nasal polyposis: A U.S. administrative claims analysis.

Background: Limited data exist on the clinical and economic burden of chronic rhinosinusitis with nasal polyposis (CRSwNP). Objective: To describe patient characteristics, health-care resource utilization (HCRU), and health-care costs among patients with CRSwNP with and without comorbid asthma (primary analysis) and with surgical management of nasal polyps (secondary analysis). Methods: This was a retrospective study of patients diagnosed with CRSwNP conducted using administrative claims data from January 1, 2013, through March 31, 2019. Study outcomes were assessed over a 2-year follow-up. Results were stratified by baseline asthma status (primary analysis) and presented separately for patients with surgically managed CRSwNP (secondary analysis). Results: The primary analysis included 10,999 patients with CRSwNP (2649 with asthma, 8350 without asthma). Patients with versus without asthma had higher medication use, HCRU, and all-cause medical costs (mean ± standard deviation $34,667 ± $42,234 versus $27,122 ± $45,573; p < 0.001) across the full follow-up period. CRSwNP-related medical costs were significantly higher for patients with versus without asthma in year 2 of follow-up. In the surgical management analysis (n = 4943), most categories of medication use and CRSwNP-related HCRU declined from baseline levels during follow-up, and CRSwNP-related pharmacy costs in year 2 were less than half of baseline levels. Conclusion: Patients diagnosed with CRSwNP and asthma had a greater burden of illness than those without asthma. Higher CRSwNP-related medical costs in year 2 of follow-up for patients with asthma may indicate worsening symptoms over time. Among patients with surgically managed CRSwNP, HCRU and costs increased in year 1 of follow-up but decreased below baseline levels in year 2, potentially reflecting improved symptom severity.

CHA2DS2-VASc Score and Stroke Prediction in Atrial Fibrillation in Whites, Blacks, and Hispanics.

Background and Purpose- Despite modest predictive ability for ischemic stroke (IS), the CHA2DS2-VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA2DS2-VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA2DS2-VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA2DS2-VASc score from addition of race/ethnicity. Methods- Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA2DS2-VASc. Results- A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA2DS2-VASc, with no race/ethnicity-based differences (P for interaction=0.17). The CHA2DS2-VASc and CHA2DS2-VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670-0.686) and 0.679 (0.671-0.688). The CHA2DS2-VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were -0.045 (95% CI, -0.067 to -0.025), 0.045 (95% CI, 0.025-0.068), and 0.016 (95% CI, 0.014-0.018). Conclusions- The predictive ability of CHA2DS2-VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA2DS2-VASc does not improve its predictive ability.

Trajectories of Cardiovascular Risk Factors and Incidence of Atrial Fibrillation Over a 25-Year Follow-Up: The ARIC Study (Atherosclerosis Risk in Communities).

BACKGROUND: Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities). METHODS: We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10 559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models. RESULTS: The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls >15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs. CONCLUSIONS: AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis.

Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

OBJECTIVE: Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. APPROACH AND RESULTS: In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. CONCLUSIONS: At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.

Mind the Gap: Hospitalizations from Multiple Sources in a Longitudinal Study.

BACKGROUND: Medicare claims and prospective studies with self-reported utilization are important sources of hospitalization data for epidemiologic and outcomes research. OBJECTIVES: To assess the concordance of Medicare claims merged with interview-based surveillance data to determine factors associated with source completeness. METHODS: The Atherosclerosis Risk in Communities (ARIC) study recruited 15,792 cohort participants aged 45 to 64 years in the period 1987 to 1989 from four communities. Hospitalization records obtained through cohort report and hospital record abstraction were matched to Medicare inpatient records (MedPAR) from 2006 to 2011. Factors associated with concordance were assessed graphically and using multinomial logit regression. RESULTS: Among fee-for-service enrollees, MedPAR and ARIC hospitalizations matched approximately 67% of the time. For Medicare Advantage enrollees, completeness increased after initiation of hospital financial incentives in 2008 to submit shadow bills for Medicare Advantage enrollees. Concordance varied by geographic site, age, veteran status, proximity to death, study attrition, and whether hospitalizations were within ARIC catchment areas. CONCLUSIONS: ARIC and MedPAR records had good concordance among fee-for-service enrollees, but many hospitalizations were available from only one source. MedPAR hospital records may be missing for veterans or observation stays. Maintaining study participation increases stay completeness, but new sources such as electronic health records may be more efficient than surveillance for mobile elderly populations.

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation.

BACKGROUND: Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. METHODS: We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. RESULTS: The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. CONCLUSION: In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Intracranial hemorrhage mortality in atrial fibrillation patients treated with dabigatran or warfarin.

BACKGROUND AND PURPOSE: In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States. METHODS: We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score-adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression. RESULTS: Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score-adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62-1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma). CONCLUSIONS: In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results.

Development of administrative data algorithms to identify patients with critical limb ischemia.

Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases (n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance.

Outcomes Following Initiation of Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol versus Multiple-Inhaler Triple Therapy Among Medicare Advantage with Part D Beneficiaries and Those Commercially Enrolled for Health Care Insurance in the United States.

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US. Methods: Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators. Results: In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant. Conclusion: FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.

COPD Exacerbations, Costs, and Health Care Resource Utilization Before and After Initiation of Fluticasone Furoate/Umeclidinium/Vilanterol in Routine Care in the USA.

Purpose: To examine the impact of initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in a single device on chronic obstructive pulmonary disease (COPD) exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related healthcare resource utilization (HCRU) and costs in patients with COPD. Methods: Retrospective database analysis of patients with COPD aged ≥40 years who initiated FF/UMEC/VI between September 1, 2017, and December 31, 2018 (index date: first pharmacy claim for FF/UMEC/VI), following evidence of multiple-inhaler triple therapy (MITT) (≥30 consecutive days) in the year prior to index. COPD exacerbations, COPD exacerbation-related costs, and all-cause and COPD-related HCRU and costs were compared between the baseline period (12 months prior to and including index) and follow-up period (12 months following index). Results: Data from 912 patients (mean [SD] age: 71.2 [8.1], 51.2% female) were included in the analyses. Among the overall cohort, mean count of total COPD exacerbations (moderate or severe) per patient was statistically significantly lower in the follow-up period compared to baseline (1.2 vs 1.4, p=0.001). The proportion of patients with ≥1 COPD exacerbation (moderate or severe) was also statistically significantly lower in the follow-up period compared to baseline (56.4% vs 62.4%, p=0.001). All-cause and COPD-related HCRU were similar during follow-up compared to baseline, although the proportion of patients with COPD-related ambulatory visits was lower during follow-up (p<0.001). COPD-related office visit costs, emergency room visit costs, and pharmacy costs were statistically significantly lower during follow-up compared to baseline (p<0.001; p=0.019; p<0.001, respectively). Conclusion: In a real-world setting, patients on MITT who subsequently initiated FF/UMEC/VI in a single device had significant reductions in the rate of COPD exacerbations (moderate or severe). Switching to FF/UMEC/VI also resulted in improvements in some HCRU and cost outcomes. These data support the use of FF/UMEC/VI among patients at high risk of exacerbation to reduce future risk and improve outcomes.

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

Clinical and economic outcomes in patients with chronic obstructive pulmonary disease initiating maintenance therapy with tiotropium bromide/olodaterol or fluticasone furoate/umeclidinium/vilanterol.

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting ß2agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304). DISCLOSURES: The study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Dr Sethi has received honoraria/fees for consulting/speaking from Astra-Zeneca, BIPI, and GlaxoSmithKline. He has received consulting fees for serving on data safety monitoring boards from Nuvaira and Pulmotect. He has received consulting fees from Apellis and Aerogen. His institution has received research funds for his participation in clinical trials from Regeneron and AstraZeneca. Ms Palli was an employee of BIPI at the time the study was conducted. Drs Clark and Shaikh are employees of BIPI. Ms Buysman and Mr Sargent are employees and Dr Bengtson was an employee of Optum, which was contracted by BIPI to conduct this study. Dr Ferguson reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants from Novartis, Altavant, and Knopp; grants and personal fees from AstraZeneca, Verona, Theravance, Teva, and GlaxoSmithKline; and personal fees from Galderma, Orpheris, Dev.Pro, Syneos, and Ionis outside the submitted work. He was a paid consultant for BIPI for this study. The authors received no direct compensation related to the development of the manuscript. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Healthcare Resource Utilization, Cost and Clinical Outcomes in Patients Diagnosed with COPD Initiating Tiotropium Bromide/Olodaterol versus Fluticasone Furoate/Umeclidinium/Vilanterol Based on Exacerbation History.

Background: ATS and GOLD guidelines recommend treating low-exacerbation risk COPD patients with dual (LAMA/LABA) agents and reserving triple therapy (TT; LAMA/LABA and inhaled corticosteroids [ICS]) for severe cases with higher-exacerbation risk. However, TT often is prescribed across the COPD spectrum. This study compared COPD exacerbations, pneumonia diagnosis, healthcare resource utilization, and costs for patients initiating tiotropium bromide/olodaterol (TIO/OLO) and a TT, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), stratified by exacerbation history. Methods: COPD patients who initiated TIO/OLO or FF/UMEC/VI between 06/01/2015-11/30/2019 (index date=first pharmacy fill-date with ≥30 consecutive treatment days) were identified from the Optum Research Database. Patients were ≥40 years old and continuously enrolled for 12 months during the baseline period and ≥30 days during follow-up. Patients were stratified into GOLD A/B (0-1 baseline non-hospitalized exacerbation), No exacerbation (subset of GOLD A/B), and GOLD C/D (≥2 non-hospitalized and/or ≥1 hospitalized baseline exacerbation). Baseline characteristics were balanced with propensity score matching (1:1). Adjusted risks of exacerbation, pneumonia diagnosis, and COPD and/or pneumonia-related utilization and costs were evaluated. Results: Adjusted exacerbation risk was similar in GOLD A/B and No exacerbation subgroups, and lower in GOLD C/D for FF/UMEC/VI versus TIO/OLO initiators (hazard ratio: 0.87; 95% CI: 0.78, 0.98, p=0.020). Adjusted pneumonia risk was similar between cohorts across the GOLD subgroups. Adjusted COPD and/or pneumonia-related population annualized pharmacy costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators across subgroups, p<0.001. Adjusted COPD and/or pneumonia-related population annualized total healthcare costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators in the GOLD A/B and No exacerbation, subgroups, p<0.001 (cost ratio [95% CI]: 1.25 [1.13, 1.38] and 1.21 [1.09, 1.36], respectively), but similar in the GOLD C/D subgroup. Conclusion: These real-world results support ATS and GOLD recommendations for treating low-exacerbation risk COPD patients with dual bronchodilators and TT for more severe, higher-exacerbation risk COPD patients.

Treatment Patterns and Disease Burden Associated with Multiple-Inhaler Triple-Therapy Use in Asthma.

BACKGROUND: Addition of a long-acting muscarinic antagonist is recommended for patients with asthma uncontrolled on inhaled corticosteroid/long-acting ß2-agonist therapy. This is the first large-scale, real-world study examining multiple-inhaler triple-therapy (MITT) use in asthma. OBJECTIVE: To describe real-world prevalence, outcomes, and treatment patterns associated with MITT. METHODS: This retrospective cohort study used medical and pharmacy claims from the Optum Research Database. Patients were diagnosed with asthma between January 01, 2013, and July 31, 2018, with evidence of MITT use (≥1 overlapping days' supply of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist). Annual MITT prevalence (primary end point) was assessed in the prevalent population; eligible patients were 18 years or older with 2 or more asthma diagnoses during the study period, and continuous enrollment for the entire year. Secondary outcomes (adherence [proportion of days covered], MITT persistence, health care resource utilization, costs) were assessed in the incident MITT population; eligible patients were 18 years or older, with 2 or more asthma diagnoses and continuous enrollment during both the 12-month baseline and 12-month follow-up periods. Patients with chronic obstructive pulmonary disease or cystic fibrosis were excluded. RESULTS: MITT prevalence was low but increased from 0.35% (95% CI, 0.32-0.37) in 2014/2015 to 1.00% (95% CI, 0.96-1.04) in 2017/2018. Among 1831 incident MITT users, there was a substantial disease burden, demonstrated by high health care resource utilization and exacerbation rates. Adherence and persistence to MITT was low (mean proportion of days covered, 0.31 ± 0.27), and 12% (n = 216) remained on MITT 12 months postinitiation. CONCLUSIONS: Overall, MITT use among patients with asthma is low. Patients initiating MITT have substantial disease burden and significant unmet needs.

Meningococcal Vaccination Rates Among People With a New Diagnosis of HIV Infection in the US.

Importance: In the United States, individuals with HIV infection have been recommended to receive a 2-dose series of the meningococcal A, C, W, Y (MenACWY) vaccine since 2016 owing to their increased risk of meningococcal disease. Objective: To examine uptake and time to receipt of the MenACWY vaccine among people with a new diagnosis of HIV. Design, Setting, and Participants: This cohort study used health insurance data from the US Optum Research Database from January 1, 2016, through March 31, 2018, to retrospectively identify 1208 individuals aged 2 years or older with 1 or more inpatient claim or 2 or more outpatient claims evidencing a new diagnosis of HIV infection and with continuous insurance enrollment for 12 or more months before and 6 or more months after diagnosis. Follow-up was 6 to 33 months. Statistical analysis was conducted from March 7, 2019, to January 5, 2022. Exposure: Receipt of the MenACWY vaccine. Main Outcomes and Measures: The coprimary outcomes were uptake and time to receipt of 1 or more doses of the MenACWY vaccine after a new HIV diagnosis. Secondary outcomes included uptake and time to receipt of 2 or more doses of the MenACWY vaccine. Vaccination uptake and receipt were estimated by Kaplan-Meier analysis; factors associated with receipt of 1 or more doses of the MenACWY vaccine were identified with multivariable Cox proportional hazards regression analysis. Results: Of 1208 individuals eligible for vaccination (1024 male patients [84.8%]; mean [SD] age, 38.8 [12.5] years; 35 [2.9%] Asian; 273 [22.6%] Black; 204 [16.9%] Hispanic; 442 [36.6%] White), 16.3% were estimated to have received a first dose of the MenACWY vaccine in the 2 years after a new HIV diagnosis. Among individuals who received a first dose, at 1 year or more of enrollment after the first dose, 66.2% were estimated to have received a second dose within 1 year of the first dose. Factors statistically significantly associated with uptake of the MenACWY vaccine included receipt of a pneumococcal vaccine (hazard ratio [HR], 23.03; 95% CI, 13.93-38.09), attendance at a well-care visit (HR, 3.67; 95% CI, 1.11-12.12), West or Midwest geographic region (West: HR, 2.24; 95% CI, 1.44-3.47; Midwest: HR, 1.78; 95% CI, 1.16-2.71), and male sex (HR, 2.72; 95% CI, 1.18-6.26), whereas age of 56 years or older was significantly associated with reduced uptake of the MenACWY vaccine (HR, 0.42; 95% CI, 0.18-0.97). Conclusions and Relevance: This cohort study suggests that MenACWY vaccine uptake among people with a new diagnosis of HIV was low, highlighting the need to educate patients and clinicians about the recommendations for conditions such as HIV infection that increase the risk of meningococcal disease among high-risk populations.

Claims-based Prevalence of Disease Progression among Patients with Fibrosing Interstitial Lung Disease Other than Idiopathic Pulmonary Fibrosis in the United States.

Rationale: Chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype is a clinical concept describing the broad group of ILDs characterized by progressive pulmonary fibrosis. The prevalence of progressive fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) is not well understood. Objectives: We used a novel algorithm to estimate the prevalence range of disease progression among patients with non-IPF fibrotic ILD in a U.S. claims database. Methods: This was a retrospective study including adults with commercial or Medicare Advantage with Part D (MAPD) insurance using administrative claims data from October 2015 to September 2019. Patients likely to have non-IPF fibrosing ILD with a progressive phenotype were identified via an algorithm that incorporated ILD-related diagnosis codes (excluding IPF) and claims-based proxies for fibrotic ILD progression, including pulmonary function tests, chest imaging, oral corticosteroid (OCS) medications, immunosuppressive medications, lung transplant, oxygen therapy, palliative care, and respiratory hospitalization. The prevalence range of non-IPF fibrotic ILD with progressive disease behavior was calculated using strict and lenient case definitions to account for potential imprecision in the progression proxies. Results: Of nearly 9 million study-eligible patients, 17,136 were identified with non-IPF fibrosing ILD. The prevalence of disease progression per 10,000 (95% confidence interval) ranged from 12.14 (11.74-12.54) to 29.05 (28.43-29.67) over a mean observation time of 1.44 years for MAPD enrollees (n = 14,686), and from 0.89 (0.81-0.97) to 2.36 (2.24-2.48) over a mean observation time of 1.29 years for commercial enrollees (n = 2,450). Prevalence estimates increased with age for both insurance types. Among patients with progression, 4,097 met at least two progression proxies not considering OCS (strict case definition) and 9,946 met at least one progression proxy (lenient case definition). The mean (standard deviation) number of proxies met was 2.1 (1.3), and the most common individual proxies met (alone or in combination with other proxies) were OCS use (48.9%), respiratory hospitalization (44.2%), and oxygen therapy (44.1%). Conclusions: This is among the first claims-based estimates of the prevalence of non-IPF chronic fibrosing ILD with a progressive phenotype. Our analysis indicates that this phenotype is rare in the overall population but increases substantially with increasing age.

Impact of timing of nintedanib initiation among patients newly diagnosed with idiopathic pulmonary fibrosis.

AIMS: While nintedanib treatment has been shown to slow the progression of idiopathic pulmonary fibrosis (IPF) in patients across varying levels of lung function, the effect of treatment timing on outcomes has not been examined. We assessed hospitalization risk and medical costs among patients with IPF based on the timing of nintedanib initiation after IPF diagnosis. MATERIALS AND METHODS: This retrospective administrative claims study included data from 04/01/2014-09/30/2019 for patients aged ≥40 years who initiated nintedanib within 1 year of IPF diagnosis. Patients were assigned to study cohorts based on the time from IPF diagnosis to nintedanib initiation. All-cause hospitalization and all-cause medical costs were modeled using marginal structural models including inverse probability weights to adjust for both baseline and time-varying characteristics. RESULTS: Of 11,195 patients diagnosed with IPF during the identification period, 449 met the study selection criteria (mean age 72.3 years, 68% male, mean follow-up time 13.3 months). Adjusted hospitalization risk and medical costs both varied significantly by the timing of nintedanib initiation (p < .001 and p = .020, respectively). Adjusted weighted hospitalization risk was higher among untreated vs. treated patients in months 2-3, months 4-6, and months 7-12 after diagnosis (hazard ratio [95% CI] 1.97 [1.09-3.56], p = .026; 2.62 [1.22-5.63], p = .014; and 5.57 [2.31-13.45], p < .001, respectively). Medical costs were 69% higher for patients initiating treatment in months 2-3 vs. month 1 (cost ratio [95% CI] 1.69 [1.20-2.38], p = .003). LIMITATIONS: Disease severity could not be assessed because clinical data were unavailable; however, proxies such as oxygen use were included to adjust for between-cohort differences in disease severity. CONCLUSIONS: Patients who initiate nintedanib promptly after IPF diagnosis may have reduced hospitalization risk and medical costs compared with those who start treatment later. Additional studies are warranted to improve understanding of the impact of prompt antifibrotic therapy on patient outcomes.

Trends and Characteristics of Global Initiative for Chronic Obstructive Lung Disease Guidelines-Discordant Prescribing of Triple Therapy Among Patients with COPD.

BACKGROUND: Triple therapy (long-acting muscarinic antagonist [LAMA] plus long-acting beta2-agonist [LABA] plus inhaled corticosteroid [ICS]) is recommended by the Global initiative for chronic Obstructive Lung Disease (GOLD) for moderate-to-severe chronic obstructive pulmonary disease (COPD) with a history of frequent and/or severe exacerbation(s) and dyspnea while using dual bronchodilators. However, many patients receive triple therapy contrary to these recommendations. This study describes factors associated with GOLD-discordant triple therapy initiation. METHODS: This retrospective analysis included patients aged 40 and above, with ≥1 COPD diagnosis, who initiated triple therapy (initiation=index date) during the period January 1, 2014 to December 31, 2018 and had ≥12 months pre-index continuous enrollment (baseline). Triple therapy comprised ≥30 days of overlapping LAMA, LABA, and ICS treatments (open triple therapy), or single-inhaler fluticasone furoate/umeclidinium/vilanterol (closed triple therapy). Cohorts were defined based on the absence of baseline maintenance medication use ("maintenance-naïve"), and/or exacerbations ("exacerbation-discordant"), or "dual-discordant" (discordant on both measures). All triple therapy initiators, overall and for each cohort, were described, and predictors of GOLD-discordant triple therapy initiation were identified. RESULTS: Among 21,711 triple therapy initiators, 34.4% were maintenance-naïve, 61.9% exacerbation-discordant, and 22.2% dual-discordant. Triple therapy initiation appeared to increase during the period 2016 to 2018. In 2018 alone, 31.9% and 58.3% of open triple therapy patients were maintenance-naïve and exacerbation-discordant, respectively, versus 37.6% and 64.4% of closed triple therapy patients. Closed triple therapy initiators had 1.65 times greater risk of dual discordance than open triple therapy initiators. Exacerbation-discordant patients initiating closed triple therapy were 1.61 times more likely to be maintenance-naïve than those initiating open triple therapy. CONCLUSION: A substantial proportion of COPD patients initiating triple therapy do not meet GOLD recommendations regarding exacerbation history and/or prior maintenance therapy. Compared with open triple therapy, closed triple therapy initiators were more likely to be dual discordant.

Burden of illness in progressive fibrosing interstitial lung disease.

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is a relatively new clinical concept describing a variety of ILDs characterized by progressive pulmonary fibrosis with associated lung function decline and worsening chest imaging. Little is known about health care resource utilization (HCRU) and costs associated with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). This study analyzed the adjusted HCRU and cost burden among patients with incident non-IPF progressive fibrosing ILD vs matched patients with incident fibrosing ILD that had not yet progressed. METHODS: This was a retrospective study of insured US adults newly diagnosed with non-IPF fibrosing ILD from October 2016 to June 2019, conducted using administrative claims data from the Optum Research Database. Progressive disease was identified using claims-based proxies comprising health care utilization associated with management of progressive fibrosing ILD. Patients in the progressive population were 1:1 propensity score matched to not-yet-progressed patients on the basis of baseline demographic and clinical characteristics. All-cause HCRU and health care costs were presented as weighted per-patient-per-month (PPPM) measures to account for variable follow-up. Differences in study outcomes between matched cohorts were evaluated using Z-tests for continuous measures and Rao-Scott tests for binary measures. RESULTS: The postmatch cohorts comprised 11,025 patients with evidence of progression matched to 11,025 patients with not-yet-progressed fibrosing ILD. Mean (SD) weighted PPPM counts of follow-up health care encounters were significantly higher for the progressive vs not-yet-progressed cohort: ambulatory visits, 4.2 (3.6) vs 3.1 (3.3); emergency department visits, 0.3 (0.5) vs 0.1 (0.3); and inpatient (IP) stays, 0.1 (0.2) vs 0.0 (0.1) (P < 0.001 for all). Among patients with an IP stay, those with progressive disease had more inpatient days than those with not-yet-progressed disease (mean [SD] 1.6 [2.4] days vs 1.0 [1.3] days, P < 0.001). Mean weighted PPPM (SD) all-cause health care costs were also significantly higher for progressive vs not-yet-progressed patients, including total costs ($4,382 [$9,597] vs $2,243 [$4,162], P < 0.001), medical costs ($3,662 [$9,150] vs $1,627 [$3,524], P < 0.001), and pharmacy costs ($720 [$2,097] vs $616 [$2,070], P = 0.002). The difference in medical costs between cohorts was driven primarily by higher inpatient costs for progressive vs not-yet-progressed patients ($1,729 [$7,557] vs $523 [$2,118], P < 0.001). CONCLUSIONS: Progressive fibrosing ILD carries a substantial economic and health care burden. Among patients with incident non-IPF fibrosing ILD, all-cause HCRU and costs were significantly higher for those with a progressive phenotype than for matched patients whose disease had not yet progressed. The cost differential was driven primarily by hospitalizations, which were longer and more frequent for the progressive cohort. Disclosures: This work was funded by Boehringer Ingelheim Pharmaceuticals, Inc. Drs Conoscenti and Shetty are employees of Boehringer Ingelheim (BI). Dr Singer was an employee of BI at the time the study was conducted. Dr Brown was a paid consultant for BI for this study. Dr Bengtson, Ms Anderson, and Dr Brekke are employees of Optum, which was contracted by BI to conduct the study. Medical writing assistance was provided by Yvette Edmonds, PhD (Optum), and was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc.