Geographic and economic influences on benralizumab prescribing for severe asthma in Japan.

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan's National Database (NDB) of insurance claims (2009-2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics' SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan's income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes.

Evaluating the relationship between health-related social needs, patient demographics, and access to biologics in patients with moderate-to-severe asthma in Bronx, NY.

OBJECTIVES: This study assesses the relationship between patient age, gender, race, socioeconomic status, social determinants of health (SDoH), and access to biologics (products isolated from natural sources that target specific molecules, proteins, and cells) in patients with moderate-to-severe asthma in Bronx, NY. METHODS: Cohort of 289 patients with moderate-to-severe asthma treated at Montefiore Medical Center (MMC) from 2018 to 2020 was used. Patient demographics, self-reported social needs, and neighborhood socioeconomic characteristics were analyzed. Neighborhood socioeconomic status was estimated by determining median income in patients' residential zip codes using 2020 Census data and grouping patients based on whether neighborhood median income was above or below New York State (NYS) median ($71,117/year). Area Deprivation Index tool (ADI) was used as an additional measure of neighborhood socioeconomic status. RESULTS: Patients living in regions with incomes below NYS median found to have longer wait times between biologic approval to administration than patients living in regions above median income (p = 0.012). Mean time from insurance approval to biologic administration was significantly different between Black and Latinx patients (p = 0.009). No significant difference found for patient regional income status and time from biologic prescription to approval. No significant differences in access to biologics were found for age, gender, number of health-related social needs, or patient ADI quartile. CONCLUSIONS: Patients who live in areas of NYC where median income is below NYS median are more likely to experience delays in access to biologics, specifically due to time between approval and administration of medication.

Frequency and economic burden of exacerbations in inhaled corticosteroid/long-acting beta-agonist-treated patients with asthma: A retrospective US claims study.

INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

Asthma patients' and physicians' perspectives on the burden and management of asthma: Post-hoc analysis of APPaRENT 1 and 2 to assess predictors of treatment adherence.

INTRODUCTION: Patient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns. METHODS: APPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020-2021. Combined data assessed adherence to maintenance medication, treatment goals, use of asthma action plans, and physician treatment patterns and preferences. Multivariable logistic regression models assessed associations between patient characteristics and both treatment prescription (by physicians) and patient treatment adherence. RESULTS: Patient and physician assessments of treatment goals and adherence differed, as did reporting of short-acting ß2-agonist (SABA) prescriptions alongside maintenance and reliever therapy (MART). Older age and greater patient-reported severity and reliever use were associated with better adherence. Patient-reported prescription of SABA with MART was associated with household smoking, severe or poorly controlled asthma, and living in China or the Philippines. CONCLUSIONS: Results revealed an important disconnect between patient and physician treatment goals and treatment adherence, suggesting that strategies for improving patient adherence to maintenance medication are needed, focusing on younger patients with milder disease. High reliever use despite good adherence may indicate poor disease control. Personalised care considering patient characteristics alongside physician training in motivational communication and shared decision-making could improve patient management and outcomes.

The Incidence, Mortality and Medical Expenditure in Patients with Asthma in Taiwan: Ten-year Nationwide Study.

BACKGROUND: This study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is limited. Our aim is to investigate incidence, mortality, prescription patterns and provide a comprehensive overview of healthcare utilization trends for asthma from 2009 to 2018. METHODS: We included patients diagnosed with asthma between 2009 and 2018. We excluded patients with missing demographic data. Our analysis covered comorbidities, including diabetes mellitus, hypertension, allergic rhinitis, eczema, atopic dermatitis, coronary artery disease, congestive heart failure, chronic kidney disease, chronic hepatitis, stroke, and cancer. Investigated medications comprised oral and intravenous steroids, short-acting beta-agonists, inhaled corticosteroids (ICS), combinations of ICS and long-acting beta-agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists montelukast. We also assessed the number of outpatient visits, emergency visits, and hospitalizations per year, as well as the average length of hospitalization and average medical costs. RESULTS: The study included a final count of 88,244 subjects from 1,998,311 randomly selected samples between 2000 and 2019. Over the past decade, there was a gradual decline in newly diagnosed asthma patients per year, from 10,140 to 6,487. The mean age annually increased from 47.59 in 2009 to 53.41 in 2018. Over 55% of the patients were female. Eczema was diagnosed in over 55% of the patients. Around 90% of the patients used oral steroids, with a peak of 97.29% in 2018, while the usage of ICS varied between 86.20% and 91.75%. Intravenous steroids use rose from 40.94% in 2009 to 54.14% in 2018. The average annual hospital stay ranged from 9 to 12 days, with a maximum of 12.26 days in 2013. Lastly, the average medical expenses per year ranged from New Taiwan dollars 5558 to 7921. CONCLUSIONS: In summary, both asthma incidence and all-cause mortality rates decreased in Taiwan from 2009 to 2018. Further analysis of medical expenses in patients with asthma who required multiple hospitalizations annually revealed an increase in outpatient and emergency visits and hospitalizations, along with longer hospital stays and higher medical costs.

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.

Changes in disease burden and treatment reality in patients with severe asthma.

BACKGROUND: Biologics are clinically available for patients with severe asthma, but changes in asthma control over time are unknown. We examined changes in disease burden and treatment in severe asthma patients. METHODS: This retrospective study used a Japanese health insurance database (Cross Fact) and included patients aged ≥16 years treated continuously with an inhaled corticosteroid (ICS) for a diagnosis of asthma in each calendar year from 2015 to 2019. Severe asthma was defined as annual use of high-dose ICS plus one or more asthma controller medications four or more times, oral corticosteroids for ≥183 days, or biologics for ≥16 weeks. Changes in asthma exacerbations, prescriptions, and laboratory testing were examined. RESULTS: Demographic characteristics were similar throughout the study. The number and proportion of patients with severe asthma among those with asthma increased (2724; 15.3% in 2015 vs 4485; 19.0% in 2019). The proportion of severe asthma patients with two or more asthma exacerbations decreased from 24.4% to 21.5%. Odds ratios (95% confidence interval) of ≥2 asthma exacerbations in each year compared with 2015 were 0.96 (0.85-1.08) in 2016 and 0.86 (0.76-0.97) in 2017, with significant reductions observed in subsequent years. Short-acting beta agonists and oral corticosteroid prescriptions for asthma exacerbations decreased and long-acting muscarinic antagonist and biologic prescriptions for maintenance treatment increased. CONCLUSIONS: This study showed improvements in disease burden and treatment in severe asthma patients. There remains an unmet medical need for patients with severe asthma, given the proportion who continue to have asthma exacerbations.

Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Targeting Asthma Remission as the Next Therapeutic Step Toward Improving Disease Control.

The long-term goal of asthma management is to achieve disease control, comprising the assessment of 2 main domains: (1) symptom control and (2) future risk of adverse outcomes. Decades of progress in asthma management have correlated with increasingly ambitious disease control targets. Moreover, the introduction of precision medicines, such as biologics, has further expanded the limits of what can be achieved in terms of disease control. It is now believed that clinical remission, a term rarely associated with asthma, may be an achievable treatment goal. An expert framework published in 2020 took the first step toward developing a commonly accepted definition of clinical remission in asthma. However, there remains a widespread discussion about the clinical parameters and thresholds that should be included in a standardized definition of clinical remission. This review aims to discuss on-treatment clinical remission as an aspirational outcome in asthma management, drawing on experiences from other chronic diseases where remission has long been a goal. We also highlight the integral role of shared decision-making between patients and health care professionals and the need for a common understanding of the individual patient journey to remission as foundational elements in reducing disease burden and improving outcomes for patients with asthma.

Cost effectiveness of omalizumab for severe asthma in Colombia.

BACKGROUND: Omalizumab is a humanized monoclonal antibody that specifically binds to free human immunoglobulin E. The introduction of this drug raises concerns about economic impact in scenarios with constrained. This study aimed to estimate the cost utility of omalizumab in adults with severe asthma uncontrolled in Colombia. METHODS: We used a Markov state-transition model to estimate the cost and QALYs associated with omalizumab compared to standard of care; from a third payer perspective over a lifetime horizon. This model used local costs while utilities were derived from international literature. Cost and transition probabilities were obtained from a mixture of Colombian-specific and internationally published data. RESULTS: The mean incremental cost of omalizumab versus standard of care is US$3 481. The mean incremental benefit of omalizumab versus standard of care 0.094 QALY. The incremental expected cost per unit of benefit is estimated at US$36846 per QALY. There is only a probability of 0.032 that Omalizumab is more cost-effective than standard of care at a threshold of US$5180 per QALY. CONCLUSION: Omalizumab is not cost-effective in adults with severe asthma uncontrolled in Colombia. If the cost of Omalizumab is reduced by 83%, this treatment would be cost-effective in our country. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Impact of income-based public drug coverage deductibles on adherence to asthma medications.

BACKGROUND: Cost-related nonadherence to medications can be a barrier to asthma management. OBJECTIVE: To quantify the impact of public drug plan deductibles on adherence to asthma medications. METHODS: We used a quasi-experimental regression discontinuity analysis to determine whether thresholds in deductibles for public drug coverage, determined on the basis of annual household income, decreased medication use among lower-income children and adults with asthma in British Columbia from 2013 to 2018. Using dispensed medication records, we evaluated deductible thresholds at annual household incomes of $15,000 (a deductible increase from 0% to 2% of annual household income), and $30,000 (a deductible increase from 2% to 3% annual household income). We evaluated medication costs, use, the ratio of inhaled corticosteroids-containing controller medications to total medications, excessive use of short-acting ß-agonists, and the proportion of days covered by controller therapies. All costs are reported in 2020 Canadian dollars. RESULTS: Overall, 88,935 individuals contributed 443,847 person-years of follow-up (57% of female sex, mean age 31 years). Public drug subsidy decreased by -$41.74 (95% CI, -$28.34 to -$55.13) at the $15,000-deductible threshold, a 28% reduction, and patient costs increased by $48.45 (95% CI, $35.37-$61.53). The $30,000 deductible threshold did not affect public drug costs (P = .31), but patient costs increased by $27.65 (95% CI, $15.22-$40.09), which is an 11% increase. Asthma-related medication use, inhaled corticosteroids-to-total medication ratio, excessive use of short-acting ß-agonists, and proportion of days covered by controller therapies were not impacted by deductible thresholds. CONCLUSION: Income-based deductibles reduced public drug costs with no effect on asthma-related medication use, adherence to controller therapies, or excessive reliever therapy use in lower-income individuals with asthma.

Cost-effectiveness and resource use analysis of patients with asthma before and after treatment with mepolizumab in a real-life setting.

OBJECTIVE: To define the cost-effectiveness and health resource use of mepolizumab in a cohort of patients with severe eosinophilic asthma in real-life conditions in Spain. METHODS: This was an observational, retrospective, single-center study. Patients included were diagnosed with severe eosinophilic asthma and treated with mepolizumab 100 mg subcutaneous (SC) 4-weekly for 12 months. Outcomes evaluated: incremental cost-effectiveness ratio (ICER), number of exacerbations, disease control with the Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), and direct and indirect cost per patient. RESULTS: 12 months after mepolizumab initiation, a significant decrease in exacerbations was shown, from a mean (standard deviation [SD]) of 3.1 (2.6) to 0.7 (1.5), an increase from 4.9 (0.4) to 6.1 (0.5) in AQLQ, and from 14.9 (5.7) to 21.5 (3.9) in ACT scores. The number of cortico-dependent patients significantly decreased from 53.3% to 13.3% during this period. There was a significant decrease of 94% in the cost of hospitalization, from a mean (SD) of €4063.9 (5423.9) pretreatment to €238.6 (1306.9) post-treatment (p = 0.0003). Total costs decreased significantly from a median of €2,423.1 (1,512.8; 9,320.9) pretreatment to €1,177.5 (965.0; 1,737.8) post-treatment if mepolizumab was excluded. ICER per exacerbation avoided was €3606.9, per 3-point ACT score increase €3934.8, and per 0.5-point AQLQ score increase €3606.9. CONCLUSIONS: Mepolizumab improves control of asthma and quality of life in patients with severe diseases in a cost-effectiveness range. The number of exacerbations decreased, and there was a clear reduction in primary care visits and hospitalizations. Further economic analyses of biological therapies for asthma are required.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Cost-effectiveness analysis of dupilumab versus omalizumab, mepolizumab, and benralizumab added to the standard of care in adults with severe asthma in Colombia.

BACKGROUND: Cost-effectiveness studies evaluate health technologies and help choose treatments. The current study compared dupilumab to omalizumab, mepolizumab, and benralizumab in Colombian adults with severe uncontrolled type 2 asthma. METHODS: Over a 5-year period, a Markov model was utilized to assess the costs of biological treatments and management of exacerbations, comparing various doses of exacerbations, comparing various doses of dupilumab, omalizumab, mepolizumab, and benralizumab as add-on treatments. It included a 5% annual discount rate per local HTA, and set willingness-to-pay at three times GDP per capita per quality-adjusted life year (QALY) in Colombia. RESULTS: Dupilumab (200 mg) exhibited greater QALYs and reduced overall costs compared to mepolizumab (100 mg), benralizumab (30 mg), and omalizumab (450 mg and 600 mg), with the incremental cost-effectiveness ratio (ICER) per QALYgained being -$5.429, -$6.269, -$196.567 and -$991.007, respectively. Dupilumab had greater QALYs and costs versus omalizumab 300 mg (ICERof $200.653 per QALY, above the willingness-to-pay threshold of 3 × GDP per capita). Sensitivity analyses were consistent with base case results. CONCLUSIONS: Dupilumab 200 mg was strongly dominant versus omalizumab 450 mg and 600 mg, mepolizumab 100 mg, and benralizumab 30 mg; however, cost-effectiveness was not demonstrated versus omalizumab 300 mg. These results could assist healthcare professionals in choosing an appropriate biologic for treating severe type 2 asthma.

Is the assessment of asthma treatment efficacy sufficiently comprehensive?

The goal of asthma guideline therapy is to achieve disease control, by minimizing impairment and decreasing the risk of exacerbations and adverse effects of the disease and its treatment. The primary objective of most clinical trials of biologics for severe asthma is a reduction in exacerbation rate. Recently, studies with patients at the lower guideline steps have also selected exacerbation reduction as a primary objective. These trials in patients with milder disease frequently demonstrate statistically significantly fewer exacerbations, but their power calculations reflect larger sample size and smaller effect size. Exacerbations have a precise consensus definition, although a minimal clinically important difference has not been established. Reduction of exacerbations in severe asthma is commonly 10-fold greater than in mild disease. Further, reduction in exacerbations is not always associated with reduced impairment. If superior control is the objective, both domains should demonstrate consistent and parallel improvement. The disconnect may reflect the need for alternative tools for measurement of impairment or, possibly, different therapeutic mechanisms of action. Determining response to biologics or discussion of disease remission requires assessing symptoms that may occur daily rather than focusing on exacerbations that occur once or twice a year for patients at the highest steps of care according to the guidelines.