Inhaled Corticosteroid/long-acting Beta-agonist Research Articles

The availability, cost, and affordability of essential medicines for asthma and COPD in low-income and middle-income countries: a systematic review

Asthma and chronic obstructive pulmonary disease (COPD) cause a considerable burden of morbidity and mortality in low-income and middle-income countries (LMICs). Access to safe, effective, quality-assured, and affordable essential medicines is variable. We aimed to review the existing literature relating to the availability, cost, and affordability of WHO's essential medicines for asthma and COPD in LMICs. A systematic review of the literature was done by searching seven databases to identify research articles published between Jan 1, 2010, and June 30, 2022. Studies on named essential medicines for asthma and COPD in LMICs were included and review articles were excluded. Two authors (MS and HT) screened and extracted data independently, and assessed bias using Joanna Briggs Institute appraisal tools. The main outcome measures were availability (WHO target of 80%), cost (compared with median price ratio [MPR]), and affordability (number of days of work of the lowest paid government worker). The study was registered with PROSPERO, CRD42021281069. Of 4742 studies identified, 29 met the inclusion criteria providing data from 60 LMICs. All studies had a low risk of bias. Six of 58 countries met the 80% availability target for short-acting beta-agonists (SABAs), three of 48 countries for inhaled corticosteroids (ICSs), and zero of four for inhaled corticosteroid-long-acting beta-agonist (ICS-LABA) combination inhalers. Costs were reported by 12 studies: the range of MPRs was 1·1-351 for SABAs, 2·6-340 for ICSs, and 24 for ICS-LABAs in the single study reporting this. Affordability was calculated in ten studies: SABA inhalers typically cost around 1-4 days' wages, ICSs 2-7 days, and ICS-LABAs at least 6 days. The included studies showed heterogeneity. Essential medicines for treating asthma and COPD were largely unavailable and unaffordable in LMICs. This was particularly true for inhalers containing corticosteroids. WHO and Wellcome Trust.

Is ethnicity a 'treatable trait' in asthma?

Is ethnicity a 'treatable trait' in asthma?

Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001–10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001–1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001–10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005–10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.

Clinical Response and Cost-Savings Associated With Generic Fluticasone Propionate/Salmeterol Multidose, Dry-Powder Inhaler in Asthma Patients Managed in an Ambulatory Care Practice Setting

Background: Fluticasone propionate/salmeterol multidose, dry powder inhaler (MDPI) was the first and only authorized generic inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination inhaler at the time of this study. This offers the potential for significant prescription cost-savings for both patients and accountable care organizations. The objective of the study was to demonstrate patients’ clinical response to generic fluticasone propionate/salmeterol MDPI when switched from one of its brand name competitors. Methods: The study was approved by the Institutional Review Board at MCPHS University. This was a prospective chart review of a large, multi-center ambulatory care organization in the Greater Boston area. Patients 12 years of age or older who were switched from a brand-name ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI were included in the study. The primary endpoint was worsened asthma control requiring a change in therapy, oral corticosteroid therapy, or hospitalization at or before 12 weeks after the inhaler was switched. Results: In total, 203 patients met inclusion criteria. Of those 203 patients, 35 had a change in therapy due to worsened asthma control (17.2% of patients, 95% CI 12.0% to 22.4%) within 12 weeks. Total projected yearly prescription cost-savings for patients who were switched and remained on the generic inhaler was $581,628. Conclusion: Eighty-three percent of patients maintained appropriate asthma control after switching from a brand ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI for 12 weeks. Switching to the generic inhaler resulted in significant prescription cost-savings for the accountable care organization.

Reduced lung elastic recoil and fixed airflow obstruction in asthma.

Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5 ) and respiratory system reactance at 5 Hz (Xrs5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), Rrs5 and Xrs5 were assessed. Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV1 /FVC: -2.6 ± 0.7) and by increased Rrs5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1 /FVC correlated negatively with K (rs = -0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = -0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction. ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795).

The Dynamics of Clinical Parameters in Romanian COPD Patients Treated With Inhaled Corticosteroid/Long-Acting Beta Agonist Regimens in a Real-World Study (RELIEF)

SESSION TITLE: COPD 2 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To describe the dynamics of clinical parameters currently evaluated by physicians in current practice, including exacerbations in chronic obstructive pulmonary disease (COPD) patients treated with inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combinations in real world practice. COPD is a progressive and irreversible disease with gradual debilitation over time and poor clinical outcomes if not appropriately treated. METHODS: RELIEF (CoRELation Between PatIENT Perception and Findings on Clinical Examination) was a non-interventional, multicenter, prospective, 12-weeks study (NCT01627743). A total number of 505 subjects participated in the study at 4 visits:at baseline and at 4, 8 and 12 weeks. Data collected included: demographics, COPD stage, medical history and clinical management, including pharmacological treatment for COPD and comorbidities. RESULTS: The majority of the subjects enrolled in RELIEF study were male (430 subjects, 85.1%). Overall, 489 subjects (96.8%) completed the study. The average age was 65 years (range: 40 to 88 years). The average duration of COPD was 5.31 years, ranging from 0 to 40 years. Majority of subjects were in group C (308 subjects, 61%); a total of 197 subjects were in group D (39%). Most of the subjects (363, 71.9%) had experienced at least 1 exacerbation of their COPD within the previous 12 months. Regarding the ICS/LABA combination used, 54.3% were using salmeterol/fluticasone, and 45.7% budesonide/formoterol. The proportions of subjects reporting signs of obstruction (prolonged expiration, sibilant rales and sonorous rales) decreased from visit 1 to visit 4. The change from visit 1 to visit 4 for sibilant rales was a significant decrease: -13.1% (p <.0001) and for sonorous rales was also a significant decrease: -19.5% (p<.0001). The percentages of patients with signs of cor pulmonale decreased from visit 1 to visit 4. The change in oedemas was a significant decrease: -4.3% (p=0.0391). The percentages of patients with respiratory insufficiency slightly decreased from visit 1 to visit 4. However, there were no significant changes from visit 1 to visit 4 regarding respiratory insufficiency and signs of hyperinflation. During the study, less than 1% of subjects reported visits to the emergency room; ≤1.1% of subjects required hospitalization and less than 1.5% of subjects visited a physician for COPD exacerbations. CONCLUSIONS: Despite the relatively short follow-up, during the 12 weeks of the study there was a significant decrease in the proportions of subjects reporting signs of airwais obstruction, cor pulmonale and number of exacerbations. No significant changes were observed in percentages of patients with respiratory insufficiency or signs of hyperinflation. CLINICAL IMPLICATIONS: This study offers insights about the impact of ICS/LABA from the first weeks of treatment on the evolution of COPD in terms of clinical improvements with relevance for patient relief such as signs of obstruction, cor pulmonale and exacerbation. DISCLOSURE: Florin Mihaltan: Consultant fee, speaker bureau, advisory committee, etc.: speaker's fees, clinical studies and congress fees The following authors have nothing to disclose: Dragos Ungureanu, Gabriela Teodorescu No Product/Research Disclosure Information

Real-World Cost Effectiveness Comparison Of Symbicort Turbuhaler And Duoresp Spiromax In UK Patients With Asthma Or Chronic Obstructive Pulmonary Disease

Objectives: To compare economic outcomes between patients with asthma or chronic obstructive pulmonary disease (COPD) receiving continuous maintenance inhaled corticosteroid/long-acting beta agonist (ICS/LABA) treatment with Symbicort and those switching from Symbicort to DuoResp. Methods: This was a historical cohort study using anonymised data from two UK primary care databases, the Optimum Patient Care Research Database and the Clinical Practice Research Datalink. Included patients had ≥ 2 years of continuous data (1-year baseline pre- and 1-year outcome post-index date). Patients switching to DuoResp were matched (1:3) with those continuing on Symbicort. Mean asthma/ COPD-related healthcare costs (medication, primary care and hospital visits) were calculated in 2014 £ and compared between groups, adjusting for confounders. Risk domain control of disease (RDC), a composite measure defining absence of exacerbations, adjusted for rhinitis, was used to assess disease control. Costeffectiveness was assessed based on total treatment costs and the absolute proportion of patients achieving RDC. Results: Patients who switched to DuoResp had lower baseline respiratory-related costs than the Symbicort group when ICS costs were included (p= 0.036). In the outcome year, switching to DuoResp was associated with significantly lower mean costs per patient in total respiratory medication (-£80; p<0.001), primary care consultations (-£13; p<0.001) and total respiratory-related costs including ICS (-£92; p<0.001). The adjusted proportion of patients achieving RDC was 58% for DuoResp versus 54% for Symbicort. Adjusted mean cost was £492 (95% CI: £461, £523) for DuoResp users and £597 (£575, £620) for Symbicort users, for a difference of -£105 (-£132, -£78) after adjusting for all baseline costs. Bootstrap sensitivity analysis found DuoResp to be less costly and more effective than Symbicort with 93.7% consistency. Conclusions: Compared with patients with asthma or COPD continuing Symbicort treatment, those switching to DuoResp demonstrated a favourable cost-effectiveness ratio in the UK primary care setting.

Use of ICS/LABA on Asthma Exacerbation Risk in Patients Within a Medical Group.

Asthma medication ratio (AMR) ≥ 0.5 has been shown to predict asthma exacerbations. This study explores the impact of increasing or decreasing inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) use over a 7-year period on achieving an AMR of ≥ 0.5. To (a) assess the impact of increasing use of ICS/LABAs on changes in a modified AMR (mAMR) and (b) examine asthma risk over time as measured by an mAMR over a 7-year period, adjusting for differences in baseline characteristics. This is a retrospective, observational study using pharmacy and medical claims from a medical group from January 1, 2003, to December 31, 2010. All patients with ≥ 1 asthma diagnosis (ICD-9-CM, 493.xx) with ≥ 1 inhaled asthma medication dispensed in each year of eligibility were included. The mAMR = total ICS controllers dispensed/(total ICS controllers dispensed + albuterol dispensed). The proportion of ICS/LABA use was determined as the number of ICS/LABA canisters dispensed/(total of ICS/LABA + ICS dispensed). Generalized linear mixed models were used to assess the effect of incremental change in ICS/LABA use on mAMR over 7 years, adjusting for differences in resource utilization, time, and asthma medication use. Nine hundred ninety patients (mean age [± SD] 34.7 years [± 18.2], 61.7% female) met all criteria. Overall, mean mAMR increased over time, while mean albuterol use decreased over time. Adjusting for covariates, we found that a 10% increase in ICS/LABA use was associated with a 9% increase (adjusted OR = 1.09, 95% CI = 1.06-1.12) in the likelihood of achieving an mAMR ≥ 0.5, while a 50% increase in ICS/LABA use was associated with a 53% increase (OR = 1.53, 95% CI = 1.31-1.80) in the likelihood of achieving an mAMR ≥ 0.5. Increase in ICS/LABA use over time in a population of asthma patients was significantly associated with a higher likelihood of achieving an mAMR ≥ 0.5.

Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.

ObjectiveResults from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations.Study Design and SettingSevere exacerbation risk was assessed over a 2-year period using claims data for patients aged ≥40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA).ResultsA total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00–1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73–1.36), or MSM analyses (HR 1.11; 95 % CI 0.68–1.81). The MSM highlighted important associations among post-index events.ConclusionNeglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0025-6) contains supplementary material, which is available to authorized users.

Comparative effectiveness of budesonide/formoterol and fluticasone/salmeterol for COPD management

Objective:To compare the effectiveness of budesonide/formoterol fumarate dihydrate (BFC) and fluticasone propionate/salmeterol (FSC), two combination inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) products approved for the treatment of chronic obstructive pulmonary disease (COPD) in the US with respect to cost, therapy adherence, and related healthcare utilization. The effectiveness of these two treatments has not previously been compared in a US COPD population.Methods:A retrospective cohort study assessed COPD-related outcomes using administrative claims data among ICS/LABA-naïve patients. Patients initiating BFC were propensity matched to FSC patients. Cost and effectiveness were measured as total healthcare expenditures, exacerbation events (hospitalizations, emergency department visits, or outpatient visits associated with oral corticosteroid or antibiotic prescription fills), and treatment medication adherence. Differences in COPD symptom control were assessed via proxy measure through claims for rescue medications and outpatient encounters.Results:Of the 6770 patients (3385 BFC and 3385 FSC), fewer BFC patients had claims for short-acting beta agonists (SABA) (34.7% vs 39.5%; p < 0.001) and ipratropium (7.8% vs 9.8%, p < 0.005) than FSC patients, but no substantial differences were seen in other clinical outcomes including tiotropium or nebulized SABA claims, COPD-related outpatient visits, or exacerbation events. There were no significant differences in total COPD-related medical costs in the 6-month period after initiation of combination therapy.Limitations:This was a retrospective observational study using claims data and accuracy of COPD diagnoses could not be verified, nor was information available on severity of disease. The results and conclusions of this study are limited to the population observed and the operational definitions of the study variables.Conclusions:For most outcomes of interest, BFC and FSC showed comparable real-world effectiveness.