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.

Association between air pollution levels and drug sales for asthma and allergy in 63 million people in metropolitan France.

INTRODUCTION: Air pollution is known to have an impact on respiratory health. However, the assessment of this relationship is far from complete and is rarely extended to the country level. We used drug sales data, both Over-The-Counter (OTC) and prescription drugs, to assess exhaustively the impact of air pollution on asthma and allergy at the national level in France. METHODS: The WHO Anatomical Therapeutic Chemical (ATC) classification system was used to describe the distribution of sales of drugs of class R03 (Drugs for obstructive airways diseases, overall for asthma) and R06 (Antihistamines for systemic use). We performed a Quasi-Poisson regression model with a generalized additive model (GAM) to estimate the relationship (Relative Risks and 95% Confidence Interval) between drug sales and air pollutants, that is Particulate Matter with a diameter less than 2.5 micrometers (PM2.5) and less than 10 micrometers (PM10) and Nitrogen dioxide (NO2), as assessed using the high-resolution CHIMERE dispersion model. We designed unadjusted and adjusted single-pollutant models as well as two-pollutant models. RESULTS: PM2.5, PM10, and NO2 were significantly and positively associated with sales of R03 and R06 class drugs, after adjustment for potential confounders. Results were confirmed in the two-pollutant model for PM10 and NO2 but not for PM2.5. CONCLUSIONS: Our study confirms the presence of an association between major air pollutants and the sales of drugs against asthma and allergies. Further studies on larger databases and over several years are necessary to confirm and better understand these results.

Cost-utility analysis of dupilumab add on therapy versus standard therapy in adolescents and adults for severe asthma in Colombia.

INTRODUCTION: Dupilumab is a recombinant human IgG4 monoclonal antibody that inhibits IL-4 and IL-13 signaling. This drug raises concerns about the economic impact in scenarios with constrained resources. This study aimed to estimate the cost-utility of dupilumab plus standard care (SoC) vs SoC alone in adolescents and adults with severe asthma and eosinophilic phenotype. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of standard therapy (ICS + LABA), add-on therapy with dupilumab, were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of $19,000. RESULTS: The base-case analysis showed dupilumab was associated with higher annual annual per-patient costs (US$5,719 for dupilumab and US$1,214 for standard therapy) and higher QALYs than standard therapy (fe  4.06 QALYs vs 3.97 QALYs, respectively). . The incremental cost-effectiveness ratio estimated was US$50,160 per QALY gained. CONCLUSION: Dupilumab is not cost-effective using a WTP of US$19000 per QALY threshold in Colombia. 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.

Cost-utility of as-needed ICS-formoterol versus to maintenance ICS in mild to moderate persistent asthma.

BACKGROUND: Recent asthma guidelines, such as the Global Initiative for Asthma (GINA), recommend in adult patients as-needed inhaled corticosteroids (ICS)-formoterol as an alternative to maintenance ICS in mild to moderate persistent asthma. The introduction of these recommendations concerns whether using as-needed budesonide-formoterol would be more cost-effective than to maintenance ICS. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared to short-acting ß2-agonist (SABA) reliever therapy in patients with mild asthma. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared to short-acting ß2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model suggests a potential gain of 0.37 QALYs and per patient per year on as-needed ICS-formoterol and a reduction in the discounted cost per person-year, of as-needed ICS-formoterol to maintenance ICS, of US$40. This position of dominance of as-needed ICS-formoterol negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic and probabilistic sensitivity analysis, our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: Low-dose budesonide-formoterol as a reliever was cost-effective when added to usual care in patients with mild asthma. 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.

Real-life cost-effectiveness of benralizumab in patients with severe asthma.

BACKGROUND: Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. METHODS: This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). RESULTS: After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. CONCLUSIONS: All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Controller Medication Use and Exacerbations for Children and Adults With Asthma in High-Deductible Health Plans.

Importance: High-deductible health plans (HDHPs) are increasingly common and associated with decreased medication use in some adult populations. How children are affected is less certain. Objective: To examine the association between HDHP enrollment and asthma controller medication use and exacerbations. Design, Setting, and Participants: For this longitudinal cohort study with a difference-in-differences design, data were obtained from a large, national, commercial (and Medicare Advantage) administrative claims database between January 1, 2002, and December 31, 2014. Children aged 4 to 17 years and adults aged 18 to 64 years with persistent asthma who switched from traditional plans to HDHPs or remained in traditional plans (control group) by employer choice during a 24-month period were identified. A coarsened exact matching technique was used to balance the groups on characteristics including employer and enrollee propensity to have HDHPs. In most HDHPs, asthma medications were exempt from the deductible and subject to copayments. Statistical analyses were conducted from August 13, 2019, to January 19, 2021. Exposure: Employer-mandated HDHP transition. Main Outcomes and Measures: Thirty-day fill rates and adherence (based on proportion of days covered [PDC]) were measured for asthma controller medications (inhaled corticosteroid [ICS], leukotriene inhibitors, and ICS long-acting ß-agonists [ICS-LABAs]). Asthma exacerbations were measured by rates of oral corticosteroid bursts and asthma-related emergency department visits among controller medication users. Results: The HDHP group included 7275 children (mean [SD] age, 10.8 [3.3] years; 4402 boys [60.5%]; and 5172 non-Hispanic White children [71.1%]) and 17 614 adults (mean [SD] age, 41.1 [13.4] years; 10 464 women [59.4%]; and 12 548 non-Hispanic White adults [71.2%]). The matched control group included 45 549 children and 114 141 adults. Compared with controls, children switching to HDHPs experienced significant absolute decreases in annual 30-day fills only for ICS-LABA medications (absolute change, -0.04; 95% CI, -0.07 to -0.01). Adults switching to HDHPs did not have significant reductions in 30-day fills for any controllers. There were no statistically significant differences in PDC, oral steroid bursts, or asthma-related emergency department visits for children or adults. For the 9.9% of HDHP enrollees with health savings account-eligible HDHPs that subjected medications to the deductible, there was a significant absolute decrease in PDC for ICS-LABA compared with controls (-4.8%; 95% CI, -7.7% to -1.9%). Conclusions and Relevance: This cohort study found that in a population where medications were exempt from the deductible for most enrollees, HDHP enrollment was associated with minimal or no reductions in controller medication use for children and adults and no change in asthma exacerbations. These findings suggest a potential benefit from exempting asthma medications from the deductible in HDHPs.

Childhood asthma in New Zealand: the impact of on-going socioeconomic disadvantage (2010-2019).

AIM: To document trends in number and cost of asthma hospital admissions and asthma prescriptions in children (0-14 years) from 2010-2019 in New Zealand. METHOD: A retrospective analysis of public hospital admission and pharmaceutical prescription data. RESULTS: The dataset included 39,731 hospitalisations with asthma as a discharge diagnosis and 5,512,856 prescriptions for asthma medication in children ≤14 years old. From 2010 to 2019, there was a 45% reduction in the number of asthma hospitalisations and an 18% reduction in prescriptions attributable to asthma. Declines were evident for both Maori and non-Maori children. However, Maori children were hospitalised with asthma at twice the rate of non-Maori children (7.2/1,000 versus 3.5/1,000, p<0.001), and a larger proportion of Maori children had an asthma readmission within 90 days of their first admission (18% versus 14%, p <0.001). Asthma admission rates for children from families living in the highest deprivation areas were, on average, 2.8 times higher than in the least deprived areas. We estimate that the combined cost of asthma hospitalisations and prescriptions was $165m. Of this, $103m was for hospital admissions and $62m was for prescriptions. CONCLUSIONS: Although hospitalisations and prescriptions attributable to asthma have declined, there are clear inequities in the health outcomes of New Zealand children with asthma. Our analysis indicates that many New Zealand children, particularly Maori children and those living in areas of high deprivation, are not receiving levels of primary care for asthma that are consistent with prevention.

Stepping down asthma treatment.

Overview of: Bloom CL, de Preux L, Sheikh A et al Health and cost impact of stepping down asthma medication for UK patients, 2001-2017: a population-based observational study. PLOS Med 2020;17:e1003145.

Clinical and economic burden of severe asthma among US patients treated with biologic therapies.

BACKGROUND: Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified. OBJECTIVE: To estimate the clinical and economic burden in a US national sample. METHODS: Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018. Inclusion criteria were continuous enrollment for 12 months postindex with a minimum of 2 biologic fills, greater than or equal to 12 years of age, evidence of medium- to high-dose inhaled corticosteroids and long-acting ß-agonist combination before the index, and absence of other respiratory diagnoses and malignancies. Disease exacerbations (used to classify asthma control), health care costs, and treatment characteristics were reported during the 12-month postindex period. RESULTS: The sample included 3262 biologic patients; 88% with anti-immunoglobulin E therapy (omalizumab) and 12% non-anti-immunoglobulin E (reslizumab, mepolizumab, benralizumab). The mean age was 49 (±15) years; 64% were women. Prescriptions included inhaled corticosteroids and long-acting ß-agonist (82%), systemic corticosteroids (76%), and leukotriene receptor antagonists (68%). Notably, 63% of patients presented greater than or equal to 1 asthma exacerbation (mean 1.3 per patient/year). Furthermore, 35% of patients were categorized as having controlled asthma, whereas 28% were suboptimally controlled and 29% were uncontrolled. Patients with uncontrolled disease had higher all-cause and asthma-related costs ($69,206 and $45,693, respectively) than patients with suboptimally controlled ($59,407 and $40,793, respectively) or controlled disease ($53,083 and $38,393, respectively). Furthermore, 62% of newly treated patients were persistent with their index biologic. CONCLUSION: Biologic therapies are effective in reducing exacerbations, but a substantial proportion of patients with severe asthma treated with current biologics continue to experience uncontrolled disease, highlighting a remaining unmet need for patients with severe uncontrolled asthma.

Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma.

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients' health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03-0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005-0.08), and number of lost working days (Δ = - 7.9, 95% CI - 11.2 to - 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI - 1588-2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (- €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

The economic burden of severe asthma in children: a comprehensive study.

OBJECTIVE: The economic burden of severe asthma (SA) in children is poorly described. We aimed to determine the healthcare costs of SA in children for the French national health insurance (NHI). METHODS: Children (6-18 years of age) with physician-confirmed diagnoses of SA or non-SA (NSA) were identified. Direct and indirect expenditures related to asthma and associated co-morbidities in the previous six months were determined, based on a physician-guided parental questionnaire and confirmed by medical records. The costs for the French NHI were assessed per child over a six month period. RESULTS: Data from 74 children, including 48 with SA (22 requiring omalizumab) and 26 with NSA, were analyzed. The global cost of SA was €3,982 per child over a six-month period, including €3,821 direct costs and €161.9 indirect costs. The global cost was €6,716 (4,220) for those requiring omalizumab vs. €1,669 (3,108) for those who did not (p < 0.01). For children with SA, 65% of direct costs were attributed to medication. Among those on omalizumab, such treatment accounted for 93% of medication costs. The global cost was 10 times higher for children with SA than those with NSA (€3,982 (4,422) vs. €363.2 (352.6), p < 0.01), and 20 times higher for children with SA on omalizumab than those with NSA (p < 0.01). CONCLUSION: The economic burden of SA in children for the French NHI is substantial and mainly driven by the most severe children requiring biologics.

Economic burden of severe asthma in Turkey: a cost of illness study from payer perspective.

Summary: Objective. To estimate economic burden of severe asthma in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods. This cost of illness study was based on identification of per patient annual direct medical costs for the management of sever easthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications. Results. Based on total annual per patient costs calculated for outpatient admission ($ 177.91), laboratory and radiological tests ($ 82.32), hospitalizations/interventions ($ 1,154.55), drug treatment/equipment ($ 2,289.63) and co-morbidities ($ 665.39) cost items, total per patient annual direct medical costrelated to management of severe asthma was calculated to be $ 4,369.76 from payer perspective. Drug treatment/equipment (52.4%) was the main cost driver in the management of severe asthma in Turkey, as followed by hospitalizations/interventions (26.4%) and co-morbidities (15.2%). Conclusions. In conclusion, our findings indicate that managing patients with severe asthma pose a considerable burden to health economics in Turkey, with medications as the main cost driver.

Cost-effectiveness of omalizumab in real world uncontrolled allergic asthma patients.

OBJECTIVE: To estimate the cost-effectiveness of omalizumab compared with standard of care in the treatment and control of severe persistent asthma, using the outcomes from the Portuguese subpopulation of the eXpeRience registry. METHODS: This was a pragmatic cost-effectiveness analysis based on real world data from the eXpeRience registry which recruited 62 patients with uncontrolled persistent allergic asthma from 20 participating centers in Portugal. Response to omalizumab treatment was measured prospectively up to 24 months by the physician's Global Evaluation of Treatment Effectiveness (GETE). Retrospective data on patients' clinical symptoms, asthma control, lung function, exacerbations, and healthcare utilization were available for up to 12 months before omalizumab initiation and served as the standard of care comparator. The number of exacerbations (severe and non-severe), the number of clinical episodes, the number of days absent from work and/or school, and GETE response to therapy were considered as effectiveness outcomes. Following a societal perspective, as cost indicators, both direct and indirect costs were considered. Direct costs relate to the cost of omalizumab, standard of care and clinical episodes (emergency room visits, hospitalizations, and unscheduled doctor visits). Indirect costs relate to the societal cost of work absenteeism. Unit costs for clinical episodes and drugs were taken from official sources within the Portuguese Health Authority. A univariate sensitivity analysis was performed. RESULTS: A rate of 1.5 exacerbations per patient-year was estimated following omalizumab treatment compared with 8.2 exacerbations per patient-year prior to omalizumab initiation, implying an 82.1% reduction in the incidence of exacerbations following omalizumab treatment relative to standard of care alone. A 54.1% reduction in GETE score was also observed in favor of omalizumab treatment. The mean cost per person-year was 3023є in the 12 months of standard of care prior to omalizumab and 16,111є in the period of treatment with omalizumab. The incremental cost-effectiveness ratios were 2244є/exacerbation avoided, and 1750є/unit decrease in GETE classification. CONCLUSION: Our results demonstrate that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations, improving overall treatment effectiveness at an acceptable cost from a societal perspective.

Inhaled Formoterol-Fluticasone Single Inhaler Therapy in Asthma: Real-World Efficacy, Budget Impact, and Potential to Improve Adherence.

Asthma is the commonest chronic disease affecting airways in humans and has an increasing global disease burden. Inhaled corticosteroids (ICS) are the first-line therapeutic option for asthma, and addition of a long-acting beta 2-agonist (LABA) has been shown to improve asthma control. A combination of the two agents in a single inhaler is beneficial with regard to ease of administration and patient compliance. Various ICS-LABA formulations are available across various countries in the world, one among them being formoterol-fluticasone. Both formoterol and fluticasone have pharmacologic peculiarities which places the combination in a uniquely advantageous position when it comes to asthma therapy. The present review focuses on some of the, hitherto, less explored aspects of this combination inhaler such as real-world efficacy, impact on budget allocation, results of switch-over therapy, and potential to improve adherence to asthma treatment. It also provides practical recommendations on positioning it in real-world asthma management.

The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK.

BACKGROUND: As-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting ß2-agonist (SABA). METHODS: A probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 µg or twice-daily budesonide 200 µg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses. RESULTS: On average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates. CONCLUSIONS: From a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.

Health and cost impact of stepping down asthma medication for UK patients, 2001-2017: A population-based observational study.

BACKGROUND: Guidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs. METHODS AND FINDINGS: We used nationwide UK primary care medical records, 2001-2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting ß2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (adjusted hazard ratio, 95% CI, p-value: ICS inhaler dose = 0.86, 0.77-0.93, p < 0.001; ICS mean daily = 0.80, 0.74-0.87, p < 0.001; LABA = 1.01, 0.92-1.11, p = 0.87, other add-on = 1.00, 0.91-1.09, p = 0.79) and no increase in reliever prescriptions (adjusted odds ratio, 95% CI, p-value: ICS inhaler dose = 0.99, 0.98-1.00, p = 0.59; ICS mean daily = 0.78, 0.76-0.79, p < 0.001; LABA = 0.83, 0.82-0.85, p < 0.001; other add-on = 0.86, 0.85-0.87, p < 0.001). Prognostic factors to initiate stepdown included medication burden, but not medication side effects. National Health Service (NHS) indicative prices were used for cost estimates. Stepping down medication, either LABAs or ICSs, could save annually around £17,000,000 or £8,600,000, respectively. Study limitations include the possibility that prescribed medication may not have been dispensed or adhered to and the reason for stepdown was not documented. CONCLUSION: In this UK study, we observed that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses. Stepping down medication did not adversely affect outcomes and was associated with substantial cost savings.