Gaps in Care Among Uncontrolled Severe Asthma Patients in the United States.

BACKGROUND: Understanding the implementation of key guideline recommendations is critical for managing severe asthma (SA) in the treatment of uncontrolled disease. OBJECTIVE: To assess specialist visits and medication escalation in US patients with SA after events indicating uncontrolled disease (EUD) and associations with health outcomes and social disparity indicators. METHODS: Patients with SA appearing in administrative claims data spanning 2015 to 2020 were indexed hierarchically on asthma-related EUD, including hospitalizations, emergency department visits with systemic corticosteroid treatment, or outpatient visits with systemic corticosteroid treatment. Patients with SA without EUD served as controls. Eligibility included age 12 or greater, 12 months enrollment before and after index, no biologic use, and no other major respiratory disease during the pre-period. Escalation of care in the form of specialist visits and medication escalation, health care resource use, costs, and disease exacerbations were assessed during follow-up. RESULTS: We identified 180,736 patients with SA (90,368 uncontrolled and 90,368 controls). Between 35% and 51% of patients with SA with an EUD had no specialist visit or medication escalation. Follow-up exacerbations ranged from 51% to 4% across EUD cohorts, compared with 13% in controls. Among uncontrolled patients with SA who were Black or Hispanic/Latino, 41% and 38%, respectively, had no specialist visit or medication escalation after EUD, compared with 33% of non-Hispanic White patients. CONCLUSIONS: A substantial proportion of uncontrolled patients with SA had no evidence of specialist visits or medication escalation after uncontrolled disease, and there was a clear relationship between uncontrolled disease and subsequent health care resource use and exacerbations. Findings highlight the need for improved guideline-based care delivery to patients with SA, particularly for those facing social disparities.

Performance of potentially inappropriate medications assessment tools in older Indian patients with cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) use are common problems in older adults. Safe prescription practices are a necessity. The tools employed for the identification of PIM sometimes do not concur with each other. METHODS: A retrospective analysis of patients ≥60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India from 2018 to 2021 was performed. Beer's-2015, STOPP/START criteria v2, PRISCUS-2010, Fit fOR The Aged (FORTA)-2018, and the EU(7)-PIM list-2015 were the tools used to assess PIM. Every patient was assigned a standardized PIM value (SPV) for each scale, which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all five tools was considered the reference standard for each patient. Bland-Altman plots were utilized to determine agreement between each scale and the reference. Association between baseline variables and PIM use was determined using multiple logistic regression analysis. RESULTS: Of the 467 patients included in this analysis, there were 372 (79.66%) males and 95 (20.34%) females with an average age of 70 ± 5.91 years. The EU(7)-PIM list was found to have the highest level of agreement given by a bias estimate of 0.010, the lowest compared to any other scale. The 95% CI of the bias was in the narrow range of -0.001 to 0.022, demonstrating the precision of the estimate. In comparison, the bias (95%) CI of Beer's criteria, STOPP/START criteria, PRISCUS list, and FORTA list were -0.039 (-0.053 to -0.025), 0.076 (0.060 to 0.092), 0.035 (0.021 to 0.049), and -0.148 (-0.165 to -0.130), respectively. Patients on polypharmacy had significantly higher PIM use compared to those without (OR = 1.47 (1.33-1.63), p = <0.001). CONCLUSIONS: The EU(7)-PIM list was found to have the least bias and hence can be considered the most reliable among all other tools studied.

Geographic variation in disease burden among patients with severe persistent asthma in the United States.

BACKGROUND: In the United States, a few studies have evaluated geographic variation of severe asthma at the subnational level. OBJECTIVE: To assess state-level geographic variation in the prevalence and characteristics of severe persistent asthma in the United States. METHODS: Patients aged above or equal to 12 years with severe persistent asthma were identified using nationally representative data from IQVIA open-source Medical/Pharmacy Claims and PharMetrics Plus databases (January 2019-December 2020). The index date was defined as the patient's earliest qualifying date for a severe asthma diagnosis. Baseline characteristics were measured during the 12-month pre-index period. Outcomes including exacerbation occurrence, asthma control, and medication use were measured during the 12-month post-index period and compared across states using census-level projections. RESULTS: A total of 2,092,799 patients with asthma were identified; 496,750 (23.7%) met criteria for severe persistent asthma and all inclusion criteria. Mean age was 50.5 years; 68.4% were females. The prevalence of severe persistent asthma varied across states, ranging from 19.6% (New Mexico) to 31.9% (Alaska). Among patients with severe persistent asthma, 40.9% had more than or equal to 1 exacerbation, ranging from 34.2% (Vermont) to 45.6% (Louisiana); 21.1% had uncontrolled disease, ranging from 16.5% (Vermont) to 24.0% (Arizona). Among patients with exacerbations, 13.7% had exacerbation-related emergency department visits or hospitalizations, ranging from 7.0% (North Carolina) to 17.7% (Nevada). Among patients with severe uncontrolled asthma, 15.6% used biologics post-index, ranging from 2.2% (Hawaii) to 27.9% (Mississippi). CONCLUSION: There is significant variability in severe persistent asthma prevalence and disease burden across US states. Reasons for geographic variation may include differences in socioeconomic/environmental factors or asthma management.

Incremental cost burden among patients with severe uncontrolled asthma in the United States.

BACKGROUND: The economic burden of severe asthma and severe uncontrolled asthma (SUA) is significant. Updated assessments of health care resource utilization (HCRU) and cost are needed given the increase in treatment options and updates to guidelines in recent years. OBJECTIVE: To describe all-cause and asthma-related HCRU and costs among patients with SUA vs patients with nonsevere asthma in the United States using real-world data. METHODS: MarketScan administrative claims databases were used to select adults with persistent asthma for this retrospective analysis between January 1, 2013, and December 31, 2019. Asthma severity status was defined using the Global Initiative for Asthma step 4/5 criteria (index is the earliest date qualifying patients as severe or randomly assigned for nonsevere patients). Patients with SUA were a subset of the severe cohort meeting the following criteria: those who were hospitalized with asthma as the primary diagnosis or had at least 2 emergency department or outpatient visits with an asthma diagnosis and a steroid burst within 7 days. HCRU, costs (allcause and asthma-related defined as medical claims with an asthma diagnosis and pharmacy claims for asthma treatment), work loss, and indirect costs due to absenteeism and short-term disability (STD) were compared between patients with SUA, severe, and nonsevere asthma. Outcomes were reported during a fixed 12-month post-index period using chi-square and t-tests where appropriate. RESULTS: 533,172 patients with persistent asthma were identified (41.9% [223,610]) severe and 58.1% [309,562] nonsevere). Of the severe patients, 17.6% (39,380) had SUA. The mean (SD) all-cause total health care costs were significantly higher in patients with SUA ($23,353 [$40,817]) and severe asthma ($18,554 [$36,147]) compared with those with nonsevere asthma ($16,177 [$37,897], P < 0.001 vs nonsevere asthma). The results were consistent for asthma-related costs. In addition, although patients with severe asthma made up 41.9% of the total study population, they contributed disproportionately higher costs (60.5%) to the total asthma-related direct costs, with the effect more evident among patients with SUA (7.4% of study population contributed 17.7% of the total asthma-related costs). For the subset of patients with asthma with workplace absenteeism, patients with SUA lost more time from work (259.3 vs 236.2 hours lost, P = 0.002; 7.8 vs 5.3 STD days, P < 0.001), and had higher corresponding indirect costs ($5,944 vs $5,415, P = 0.002 for absenteeism related; $856 vs $582, P < 0.001 for STD related) compared with patients with nonsevere asthma. CONCLUSIONS: Patients with SUA have significantly higher asthma-related economic burden compared with patients with nonsevere asthma and contribute a disproportionally higher percentage of asthma-related costs. DISCLOSURES: This study was funded by Amgen and AstraZeneca. The design and analysis for this study was conducted primarily by Merative. Amgen and AstraZeneca provided funding to support protocol development, data analysis, and manuscript development activities associated with this study. Dr Burnette is on the advisory board and a consultant for GSK, a consultant and member of the advisory boards and speakers' bureaus of Sanofi, Genzyme, Regeneron, AstraZeneca, and Amgen Inc. Dr Wang, Dr Rane, Dr Lindsley, and Dr Llanos are employees and shareholders of Amgen Inc. Dr Chung and Dr Ambrose are employees and shareholders of AstraZeneca. Ms Princic and Ms Park are employees of Merative, which received funding from Amgen to conduct this study.

A prospective, open-label, randomised, parallel design study of 4 generic formulations of intramuscular L-asparaginase in childhood precursor B-cell acute lymphoblastic leukaemia (ALL).

AIMS: L-asparaginase is an essential medicine for childhood ALL. The quality of generic L-asparaginase available in India is a matter of concern. We compared four commonly used generic formulations of L-asparaginase in India. MATERIALS AND METHODS: We conducted a prospective, open-label, randomised trial of four generic formulations of asparaginase for the treatment of patients with newly diagnosed intermediate-risk B-ALL. Patients were randomly assigned in a 1:1:1:1 ratio to receive generic asparaginase at a dose of at 10,000 IU/m 2 on days 9, 12, 15, and 18 of a 35-day cycle (Induction treatment). The primary end points were to determine the difference in the asparaginase activity and asparagine depletion. Historical patients who received L-asparaginase Medac (innovator) served as controls. RESULTS: A total of 48 patients underwent randomization; 12 patients each in the four arms. Failure to achieve predefined activity threshold of 100 IU/L was observed in 9/40 samples of Generic A (22·5%), 23/40 of Generic B (57·5%), and 43/44 (98%) each of Generic C and D. All 27 samples from seven historical patients who were administered Medac had activity > 100 IU/L. The average activity was significantly higher for Genericm A, 154 (70·3, 285·4) IU/L followed by Generic B 84·5(44·2, 289·1) IU/L, Generic C 45(14·4, 58·4) IU/L, and Generic D 20·4(13, 35) IU/L. Only 6 patients had asparaginase activity > 100 IU/L on each of the four occasions (Generic A = 5; Generic B = 1), and none of them developed Anti-Asparaginase Antibodies (AAA). On the other hand, AAA was observed in 12/36 patients who had at least one level < 100 IU/L (P < 0·05): Generic A 3/5, Generic B = 3/9, Generic D (4/11), and Generic C (5/11). CONCLUSION: Generic A and B had better trough asparaginase activity compared to Generic D and C. Overall, generic formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until strict regulatory enforcement improves the quality of these generics, dose adaptive approaches coupled with therapeutic drug monitoring need to be considered.

Economic Distress of Breast Cancer Patients Seeking Treatment at a Tertiary Cancer Center in Mumbai during COVID-19 Pandemic: A Cohort Study.

BACKGROUND: Cancer treatment during nationwide lockdown due to the COVID-19 pandemic has posed several challenges in the delivery of cancer care and carries tremendous potential sequel of impoverishing the households. This study aims to examine the economic distress faced by breast cancer patients receiving treatment at Tata Memorial Center (TMC) Mumbai, India during the nationwide lockdown initiated in March 2020 following the outbreak of COVID-19. METHODS: A total of 138 non-metastatic breast cancer patients who were accrued in this study at TMC before imposing of lockdown, and their treatment was impacted because of the COVID-19 outbreak, were interviewed. Telephonic interviews were conducted using a structured schedule which contained information on household and demographic characteristics of the patients, knowledge about COVID-19, their daily expenditure for treatment, difficulties faced during lockdown and how they met expenditures. Descriptive statistics and logistic regression were used in the analyses. RESULTS: The average monthly expenditure of cancer patients had increased by 32% during the COVID-19 period while the mean monthly household income was reduced by a quarter. More than two-thirds of the patients had no income during the lockdown. More than half of the patients met their expenditure by borrowing money, 30% of the patients used their savings, 28% got charity and 25% used household income. About 81% of the patients had reported shortage of money, 32%  reported shortage of food and 28% reported shortage of medicine. The distress financing was significantly higher among patients receiving treatment in Mumbai compared to those receiving treatment at their native cities (67% vs. 46%), patients under 40 years of age, illiterate, currently married, Muslim and staying at a rented house. CONCLUSION: The incremental expenditure coupled with reduced or no income due to the closure of economic activities in the country imposed severe financial stress on breast cancer patients.

Patient Characteristics and Treatment Patterns among Medicare Beneficiaries Initiating PCSK9 Inhibitor Therapy.

PURPOSE: There is limited real-world evidence around use of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) among US older adults. This study examined baseline characteristics of fee-for-service (FFS) Medicare beneficiaries newly initiating PCSK9i therapy during the period immediately following market availability. METHODS: This cross-sectional study used Medicare claims (2013-2016) to identify 5051 FFS Medicare beneficiaries who filled ≥ 1 PCSK9i prescription between August 2015 and December 2016. We analyzed patient demographics, clinical characteristics, and baseline healthcare expenditures in the 12-month period prior to PCSK9i initiation, for these beneficiaries. RESULTS: Most beneficiaries initiating PCSK9i were female (57%), < 75 years of age (61%), white (89%), and lived in metropolitan areas (83%). At baseline, these PCSK9i initiators had 6 chronic conditions on average, with conditions such as hyperlipidemia, hypertension, and ischemic heart disease being most prevalent. Approximately 88% had a diagnosis of atherosclerotic cardiovascular disease (ASCVD), and 14% experienced acute cardiovascular events during the 12-month baseline period. Use of any statin and/or ezetimibe ranged from 54 to 76% in the 6-month and 24-month baseline period. Their total annual Medicare expenditures averaged US$17,552, of which most were attributable to ambulatory care and prescription use, in the 12-month baseline period. CONCLUSION: High burden of cardiovascular conditions and prescription expenditures at baseline were common among FFS beneficiaries initiating PCSK9i therapy. These findings suggest that physicians prescribe PCSK9i to elderly patients at high risk for adverse cardiovascular events. Considering the evolving treatment landscape, PCSK9i utilization might increase in Medicare.

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.

PURPOSE: To describe patient characteristics and treatment patterns among early initiators of proprotein convertase subtilisin/kexin type nine inhibitors (PCSK9is) who initiated treatment within the first 6 months of market availability. PATIENTS AND METHODS: This retrospective cohort study used IQVIA's longitudinal open-source point-of-sale pharmacy claims database (LRx) and PharMetrics Plus (P+) health plan claims database to identify patients initiating a PCSK9i between January 1, 2016 and June 30, 2016. The index date was defined as the date of the first PCSK9i prescription (index claim) during the enrollment window; patients were followed for ≥6 months postindex. Patient characteristics including use of baseline lipid-lowering therapy (LLT) and measures such as persistence and adherence to PCSK9i therapy were evaluated with respect to health plan type (commercial vs Medicare). RESULTS: Overall, patients initiating PCSK9i (n=13,151) had a mean age of 66 years, and 51% were male. Approximately 67.4% of patients used some form of LLT (statin and/or ezetimibe) in the 24 months prior to initiating PCSK9i therapy. The proportion of patients covered by a commercial health plan (51.2%) was similar to that covered by Medicare (48.8%). Persistence on PCSK9i was marginally longer for patients with commercial insurance than Medicare (mean days on therapy 202.2 vs 198.5). Overall, 42.6% of patients discontinued their PCSK9i during the 180 days of follow-up. CONCLUSION: This study demonstrates that a large proportion of patients discontinue PCSK9i therapy at 30 and 90 days, which are the time frames for which many health plans require recertification to continue access to PCSK9i. Future studies looking at treatment patterns among patients who initiate PCSK9i therapy after the first 180 days once health plan formularies and utilization management criteria were finalized are needed to understand more comprehensively real-world PCSK9i usage patterns.

Treatment and Survival of Medicare Beneficiaries with Colorectal Cancer: A Comparative Analysis Between a Rural State Cancer Registry and National Data.

The aim was to examine and compare with "national" estimates, receipt of colorectal cancer (CRC) treatment in the initial phase of care and survival following a CRC diagnosis in rural Medicare beneficiaries. A retrospective study was conducted on fee-for-service Medicare beneficiaries diagnosed with CRC in 2003-2006, identified from West Virginia Cancer Registry (WVCR)-Medicare linked database (N = 2119). A comparative cohort was identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare (N = 38,168). CRC treatment received was ascertained from beneficiaries' Medicare claims in the 12 months post CRC diagnosis or until death, whichever happened first. Receipt of minimally appropriate CRC treatment (MACT) was defined using recommended CRC treatment guidelines. All-cause and CRC-specific mortality in the 36-month period post CRC diagnosis were examined. Differences in usage of CRC surgery, chemotherapy, and radiation were observed between the 2 populations, with those from WVCR-Medicare being less likely to receive any type of CRC surgery (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = [0.73-0.93]). Overall, those from WVCR-Medicare had a lower likelihood of receiving MACT, (AOR = 0.85; 95% CI = [0.76-0.96]) compared to their national counterparts. Higher hazard of CRC mortality was observed in the WVCR-Medicare cohort (adjusted hazard ratio = 1.26; 95% CI = [1.20-1.32]) compared to the SEER-Medicare cohort. Although more beneficiaries from WVCR-Medicare were diagnosed in early-stage CRC compared to their SEER-Medicare counterparts, they had a lower likelihood of receiving MACT and a higher hazard of CRC mortality. This study highlights the need for an increased focus on improving access to care at every phase of the CRC care continuum, especially for those from rural settings.

The impact of formulary drug exclusion policies on patients and healthcare costs.

OBJECTIVES: In an attempt to increase the efficiency of their drug benefit policies, insurers are increasingly excluding drugs from their formularies that they deem to be of low value. Our objective was to identify and review empirical evaluations of drug exclusion policies and examine how they affected patients and healthcare costs. STUDY DESIGN: Literature review. METHODS: We performed a literature search to identify empirical studies that evaluated drug exclusion policies. We reviewed each study to determine how the policy impacted patients (ie, if disease control or frequency, or severity of symptoms, were affected) and if healthcare costs (eg, drug expenditures and costs associated with physician office visits, hospitalizations, laboratory tests) changed. RESULTS: We included 26 studies pertaining to 27 drug exclusion policies. Twenty studies reported the impact of 21 drug exclusion policies on patients: 6 (28.6%) policies were reported to have had a positive impact, 6 (28.6%) to have had a negative impact, and 9 (42.8%) to not have impacted patients. Eighteen studies reported the impact of 19 drug exclusion policies on overall healthcare costs: 14 (73.7%) policies were reported to have reduced costs, 1 (5.3%) to have had a neutral impact on costs, and 4 (21.1%) to have increased costs. CONCLUSIONS: Although there were important exceptions, most studies found that drug exclusion policies reduced costs and did not negatively impact patients.

Costs of COPD exacerbations in the emergency department and inpatient setting.

BACKGROUND: Exacerbations of COPD contribute to lung function decline and reduced quality of life. Treatment of exacerbations in the hospital setting is costly, but information concerning the component cost drivers of this care is scarce. Our objective was to describe and characterize costs of COPD care in the hospital setting. METHODS: Administrative data from 602 hospitals were used to calculate 2008 costs for COPD-related emergency department (ED) visits, simple inpatient admissions and complex admissions (categorized as intubation/no intensive care, intensive care/no intubation, or intensive care/intubation) among COPD patients' age ≥ 40 years. Inpatient mortality, length of stay (LOS), and readmission rates in 2005-2008 were also calculated. RESULTS: Mean 2008 costs were $647 (SD $445) for ED visits (n = 24,617), $7242 ($7987) for simple admissions (n = 42,734), and $20,757 ($41,370) for complex admissions (n = 4142). Intensive care/intubation admissions incurred the highest costs ($44,909 [SD, $80,351]; n = 838). Complex admissions accounted for 5.8% of hospital-based COPD care in 2008, but 20.9% of costs. Mean LOS ranged from 4.5 days (SD 3.3) for simple admissions to 16.0 days (16.7) for intensive care/intubation admissions. Death occurred in 0.9% of simple admissions, 10.3% of all complex admissions, and 26.5-39.1% of admissions involving intubation. Readmission rates within 30-60 days for ED visits, simple admissions and complex admissions were 17.8%, 15.3% and 15.7%, respectively. From 2005 to 2008, trends in LOS were relatively flat; inflation-adjusted costs increased 4.0-5.9%. CONCLUSIONS: Costs of hospital-based care for COPD are substantial. Admissions involving intubation or intensive care are associated with the highest costs, LOS, and mortality.

Costs of inpatient and emergency department care for chronic obstructive pulmonary disease in an elderly Medicare population.

OBJECTIVE: Treatment in the hospital setting accounts for the largest portion of healthcare costs for COPD, but there is little information about components of hospital care that contribute most to these costs. The authors determined the costs and characteristics of COPD-related hospital-based healthcare in a Medicare population. METHODS: Using administrative data from 602 hospitals, 2008 costs of COPD-related care among Medicare beneficiaries age ≥ 65 years were calculated for emergency department (ED) visits, simple inpatient admissions and complex admissions (categorized as intubation/no intensive care, intensive care/no intubation, and intensive care/intubation) in a cross-sectional study. Rates of death at discharge and trends in costs, length of stay and readmission rates from 2005 to 2008 also were examined. MAIN RESULTS: There were 45,421 eligible healthcare encounters in 2008. Mean costs were $679 (SD, $399) for ED visits (n = 10,322), $7,544 ($8,049) for simple inpatient admissions (n = 25,560), and $21,098 ($46,160) for complex admissions (n = 2,441). Intensive care/intubation admissions (n = 460) had the highest costs ($45,607, SD $94,794) and greatest length of stay (16.3 days, SD 13.7); intubation/no ICU admissions had the highest inpatient mortality (42.1%). In 2008, 15.4% of patients with a COPD-related ED visit had a repeat ED visit and 15.5-16.5% of those with a COPD-related admission had a readmission within 60 days. From 2005 to 2008, costs of admissions involving intubation increased 10.4-23.5%. Study limitations include the absence of objective clinical data, including spirometry and smoking history, to validate administrative data and permit identification of disease severity. CONCLUSIONS: In this Medicare population, COPD exacerbations and related inpatient and emergency department care represented a substantial cost burden. Admissions involving intubation were associated with the highest costs, lengths of stay and inpatient mortality. This population needs to be managed and treated adequately in order to prevent these severe events.