ICS-containing Regimens Research Articles

Regular versus as-needed treatments for mild asthma in children, adolescents, and adults: a systematic review and network meta-analysis

BackgroundInhaled corticosteroids (ICS) are recommended treatment for mild asthma. We aimed to update the evidence on the efficacy and safety of ICS-containing regimens, leukotriene receptor antagonists (LTRA), and tiotropium relative to as-needed (AN) short-acting β2-agonists (SABA) in children (aged 6–11 years) and adolescents/adults.MethodsA systematic review of randomized controlled trials (RCTs) of regular and AN treatment for mild asthma was conducted (CRD42022352384). PubMed, Scopus, and ClinicalTrials.gov were searched up to 31st March 2024. RCTs in children or adolescents/adults with mild asthma were eligible if they compared any of the following treatments: ICS alone or in combination with fast-acting bronchodilators (FABA, i.e., formoterol or SABA) or long-acting β2-agonists (LABA), LTRA, tiotropium, and SABA alone, for the following outcomes: exacerbations, asthma symptoms, forced expiratory volume in 1 s (FEV1), asthma-specific quality-of-life (QoL), or severe adverse events (SAEs). The two-stage network meta-analysis (NMA) was used to pool risk ratios (RR) or mean differences for treatment outcomes. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). This review followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2.ResultsThirteen RCTs in children and 29 in adolescents/adults were included. Regular ICS ranked best for preventing exacerbations and improving FEV1 in children. NMA of RCTs suggested regular ICS were better in preventing exacerbations than LTRA (RR [95% confidence intervals], (0.81 [0.69,0.96]) and AN-SABA (0.61 [0.48,0.78]), and not different from AN-ICS (0.83 [0.62,1.12]). In adolescents/adults, for preventing severe exacerbations, regular ICS outperformed AN-SABA (0.58 [0.46,0.73]), but AN-ICS/FABA (0.73 [0.54,0.97]), and regular ICS/LABA (0.68 [0.48,0.97]) surpassed regular ICS. Symptom relief and improved FEV1 were not different among the ICS-containing regimens. Regular ICS ranked best for improved QoL and least likely for SAEs.ConclusionsRegular ICS use may be the most effective treatment for preventing exacerbation and increasing FEV1 in children with mild asthma. In adolescents/adults, ICS-containing regimens outperformed AN-SABA for exacerbation prevention. With varying degrees of heterogeneity, severe exacerbation risk in adolescents/adults might be lower with regular ICS/LABA or AN-ICS/FABA than regular ICS, where AN-ICS/FABA may not be suitable for patients with low FEV1. Additionally, regular ICS use may enhance FEV1 and QoL more than AN-SABA and LTRA.

Lack of Association between Inhaled Corticosteroid Use Based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. We retrospectively analyzed 107 COPD patients without a history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion (ppb) were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. The median FeNO value was 32 ppb (interquartile range, 19 to 45) and 34 (20.0%) patients were classified as high FeNO group (median 74 ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥300 cells/μL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01 to 6.91; p=0.049). High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

IntroductionInhaled corticosteroids (ICS) are often prescribed inappropriately alongside long-acting bronchodilators for chronic obstructive pulmonary disease (COPD). We aimed to investigate if prescribing habits in the US and UK differ from recommendations for initiation of COPD maintenance therapy.MethodsWe used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases to assess exacerbations and comorbidities in patients with COPD initiating first maintenance therapy (1MT) between 2015 and 2018. Patients with a recorded asthma diagnosis prior to initiation of 1MT were excluded. We evaluated time from recorded diagnosis of COPD until initiation of 1MT, and treatment regimen at 1MT (long-acting muscarinic antagonist [LAMA], long-acting β2-agonist [LABA], ICS, as monotherapy or in combination).ResultsIn the US and UK, median (IQR) time between recorded COPD diagnosis and 1MT was 158 (12; 839) and 29 (1; 521) days, respectively. Among the 53,473 US patients and 8786 UK patients who initiated 1MT, 50.9% and 32.4% had ≥ 1 exacerbation in the previous year. In the US, 20% of patients initiated LAMA, 1% LABA, 13% LAMA/LABA, and 66% an ICS-containing regimen (49% LABA/ICS, 13% ICS, and 4% LAMA/LABA/ICS). In the UK, 53% of patients initiated LAMA, 4% LABA, 16% LAMA/LABA, and 27% an ICS-containing regimen (14% LABA/ICS, 9% ICS, and 4% LAMA/LABA/ICS).ConclusionsAt 1MT, two-thirds of patients in the US received ICS-containing therapies, with almost half on LABA/ICS. In contrast, less than one-third received ICS-containing therapy in the UK and more than half of patients received LAMA. In both countries, more patients received ICS-containing therapies at initiation of 1MT than would be expected based on their exacerbation history, suggesting overprescribing.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00179-0.

Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases

IntroductionPrevious studies have reported that more patients receive inhaled corticosteroid (ICS)-containing therapies than would be expected based on exacerbation history, suggesting overprescribing. We aimed to describe patterns of treatment switching from first (1MT) to second maintenance therapy (2MT) among COPD patients in the US and UK.MethodsWe used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases (2015 – 2018) to assess transitions between 1MT and 2MT among COPD patients. Patients with a recorded asthma diagnosis prior to 1MT were excluded. We assessed whether prescribed treatments (long-acting muscarinic antagonists [LAMA], long-acting β2-agonists [LABA], inhaled corticosteroids [ICS], as monotherapy or in combination) were consistent with global and national recommendations for COPD, identified patient characteristics associated with treatment transitions, and evaluated treatment duration.ResultsOverall, 7028 patients in the US and 2461 in the UK initiated 2MT within a median (IQR) 160.0 (76.0; 335.0) and 218.0 (86.0; 428.0) days after 1MT, respectively. In the US, 33.6% of patients initiating 2MT had no recorded exacerbations in the previous year, whereas 23.1% had one and 43.3% had ≥ 2. In the UK, 54.9% of patients had no recorded exacerbations in the previous year, whereas 20.9% had one and 24.2% had ≥ 2. At 2MT, most patients switched to LAMA/LABA/ICS (26.1%) or LABA/ICS (25.8%) in the US, and LAMA/LABA (39.4%) or LAMA/LABA/ICS (27.8%) in the UK; 62.2% (US) and 47.5% of patients (UK) were prescribed ICS-containing regimens. The most common treatment transition from 1MT to 2MT was LABA/ICS to LAMA/LABA/ICS (13.0%) in the US; and LAMA to LAMA/LABA (32.5%) and LAMA to LAMA/LABA/ICS (14.3%) in the UK.ConclusionsAt 2MT, the proportion of patients on LAMA/LABA/ICS was similar between the US and UK, but treatment pathways were different.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00180-7.

Inhaled Corticosteroid Treatment Regimens and Health Outcomes in a UK COPD Population Study.

BackgroundInhaled corticosteroids (ICS) are a prevailing treatment option for COPD patients but recent guidelines have relegated their use predominantly to patients with frequent exacerbations. Yet large numbers of patients worldwide are currently treated with ICS-containing regimens. We wished to determine in routine clinical practice how common ICS withdrawal is and the differences in health outcomes between patients managed on ICS-containing and non-ICS containing regimens.Patients and MethodsCOPD patients were identified from the UK primary care electronic healthcare records, between 2014 and 2018. Patients were grouped into three treatment regimens: long-acting beta-agonist (LABA) and inhaled corticosteroids (ICS), LABA and long-acting muscarinic antagonist (LAMA), and triple therapy (LABA, LAMA and ICS). Annual incidence of ICS withdrawal was measured. Multivariable logistic regression was used to identify patient factors associated with withdrawal. Multivariable Poisson regression was used to assess the association of exacerbations and hospitalised pneumonia between the ICS-containing regimens (LABA-ICS and triple therapy) and patients prescribed LABA-LAMA.ResultsOf 117,046 patients, around three-quarters were prescribed ICS-containing inhalers but ICS withdrawal occurred annually in only approximately 2–3% of patients. Exacerbations in the past year, but not a past history of pneumonia, were associated with ICS withdrawal. A total of 31,034 patients using three treatment regimens (LABA-ICS, LABA-LAMA or triple therapy) were assessed for their relative risk of exacerbations and pneumonia; the exacerbation risk was slightly lower in LABA-ICS users but the same in triple therapy users, as compared to LABA-LAMA users (LABA-ICS adjusted IRR=0.82 (95% CI 0.73–0.93), triple adjusted IRR=0.99 (95% CI 0.88–1.11)). There was no difference in the pneumonia risk (LABA-ICS adjusted IRR=0.96 (95% CI 0.71–1.31), triple adjusted IRR=1.16 (95% CI 0.87–1.57)).ConclusionUse of ICS-containing inhaled medication is prevalent across the UK while ICS withdrawal from established treatment was relatively uncommon. Exacerbations and pneumonia risk was similar between the ICS-containing and non-ICS containing treatment regimens.

Inhaled Corticosteroid-Containing Regimens Reduce Hospitalizations and Healthcare Costs among Elderly Asthmatics: Real-World Validation Using the National Health Insurance Claims Database.

The high rates of mortality and hospitalization among elderly asthmatics, as well as their increasing healthcare costs have become an important public health issue. It would be worthwhile to assess whether inhaled corticosteroid (ICS) can resolve these problems. To explore ICS prescription rates for elderly asthmatics and the factors influencing them and to investigate their association with hospitalization and healthcare costs, we analyzed data from the National Health Insurance Claims Database for the same time frame (December 1 to February 28) across three different periods (2011-2012; 2014-2015; and 2017-2018), from which we identified 6,619, 5,619, and 6,880 elderly individuals, respectively. The prescription rates of ICS increased (52.8%, 65.5% and 68.8%, in the first, second and third survey period, respectively) and inversely the hospital admission rates declined (3.7%, 3.2% and 2.5%, in the first, second and third survey period, respectively). The total healthcare costs per month were significantly lower for patients who received ICS-containing regimens than for those who did not. A multivariate analysis revealed that increasing age, rural residence, receiving a prescription from a clinic, hospital admission, and prescription of asthma medications other than ICS were associated with non-prescription of ICS, whereas cross-boundary treatment increased the ICS-prescription rate. Our study suggests that increases in the prescription rate of ICS are associated with reduced hospital admission rates and lower medical costs in the real-world. ICS prescription rates in rural areas and at clinics, which remain low, need to be increased.

Are there specific clinical characteristics associated with physician\u2019s treatment choices in COPD?

BackgroundThe number of pharmacological agents and guidelines available for COPD has increased markedly but guidelines remain poorly followed. Understanding underlying clinical reasoning is challenging and could be informed by clinical characteristics associated with treatment prescriptions.MethodsTo determine whether COPD treatment choices by respiratory physicians correspond to specific patients’ features, this study was performed in 1171 patients who had complete treatment and clinical characterisation data. Multiple statistical models were applied to explain five treatment categories: A: no COPD treatment or short-acting bronchodilator(s) only; B: one long-acting bronchodilator (beta2 agonist, LABA or anticholinergic agent, LAMA); C: LABA+LAMA; D: a LABA or LAMA + inhaled corticosteroid (ICS); E: triple therapy (LABA+LAMA+ICS).ResultsMean FEV1 was 60% predicted. Triple therapy was prescribed to 32.9% (treatment category E) of patients and 29.8% received a combination of two treatments (treatment categories C or D); ICS-containing regimen were present for 44% of patients altogether. Single or dual bronchodilation were less frequently used (treatment categories B and C: 19% each). While lung function was associated with all treatment decisions, exacerbation history, scores of clinical impact and gender were associated with the prescription of > 1 maintenance treatment. Statistical models could predict treatment decisions with a < 35% error rate.ConclusionIn COPD, contrary to what has been previously reported in some studies, treatment choices by respiratory physicians appear rather rational since they can be largely explained by the patients’ characteristics proposed to guide them in most recommendations.

Discontinuation of therapy among COPD patients who experience an improvement in exacerbation status.

A subset of patients with chronic obstructive pulmonary disease (COPD) experience a decrease in exacerbation frequency, leading to a diminished need for treatment with inhaled corticosteroids (ICS). We investigated prescribing and discontinuation patterns of long-acting bronchodilators and ICS in COPD patients according to exacerbation frequency. Using the nationwide Danish health registries, we conducted a drug utilization study among patients who had at least two exacerbations or one hospitalization due to an exacerbation during 2011-2012. This study population was stratified according to consistency of exacerbation occurrence after 12, 24, 36, and 48months of follow-up and the groups were described according to use of ICS, long-acting β2-agonists (LABA), and long-acting anticholinergics (LAMA), and combinations thereof. We identified 29,010 COPD exacerbators during 2011-2012. Upon inclusion, 70% received ICS-containing regimens, in combination with LABA (23%) or both LABA and LAMA (41%). The proportion of prevalent users of ICS-containing regimens decreased to 56% during follow-up among exacerbation-free individuals, while it increased to 86% in individuals who experienced at least one exacerbation annually. Persistence to ICS-containing regimens was 58% after 4years in individuals without exacerbations compared to 74% among those with annual exacerbations. Similar patterns were observed for triple therapy which was the most extensively used drug combination regardless of consistency of exacerbation occurrence. The extensive use of ICS and the relatively high persistence to ICS-containing regimens in individuals who had a decrease in exacerbation occurrence highlight a need for the development and implementation of de-escalation strategies in clinical practice.

Alignment of Inhaled Chronic Obstructive Pulmonary Disease Therapies with Published Strategies. Analysis of the Global Initiative for Chronic Obstructive Lung Disease Recommendations in SPIROMICS.

Despite awareness of chronic obstructive pulmonary disease (COPD) treatment recommendations, uptake is poor. The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) spans 2010-2016, providing an opportunity to assess integration of 2011 Global Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in a large observational cohort study. To evaluate how COPD treatment aligns with 2011 GOLD strategies and determine factors associated with failure to align with recommendations. Information on inhaled medication use collected via questionnaire annually for 4 years was compiled into therapeutic classes (long-acting antimuscarinic agent, long-acting β-agonist, inhaled corticosteroids [ICS], and combinations thereof). Medications were not modified by SPIROMICS investigators. 2011 GOLD COPD categories A, B, C, and D were assigned. Alignment of inhaler regimen with first-/second-line GOLD recommendations was determined, stratifying into recommendation aligned or nonaligned. Recommendation-nonaligned participants were further stratified into overuse and underuse categories. Of 1,721 participants with COPD, at baseline, 52% of regimens aligned with GOLD recommendations. Among participants with nonaligned regimens, 46% reported underuse, predominately owing to lack of long-acting inhalers in GOLD category D. Of the 54% reporting overuse, 95% were treated with nonindicated ICS-containing regimens. Among 431 participants with 4 years of follow-up data, recommendation alignment did not change over time. When we compared 2011 and 2017 recommendations, we found that 47% did not align with either set of recommendations, whereas 35% were in alignment with both recommendations. Among SPIROMICS participants with COPD, nearly 50% reported inhaler regimens that did not align with GOLD recommendations. Nonalignment was driven largely by overuse of ICS regimens in milder disease and lack of long-acting inhalers in severe disease.

Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice.

Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD. While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with – according to Belgian market research data – up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist. Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD. However, historical habits appear difficult to change even in the light of recent scientific evidence. We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter.

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B: an observational study using the Clinical Practice Research Datalink (CPRD)

BackgroundRecent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it is known that ICS is frequently prescribed for patients with less severe COPD. Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use. The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen.MethodsLinked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing. Treatment acquisition costs were not assessed.ResultsResults showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine outcomes assessed. Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 < 50% predicted), one prior exacerbation or elevated blood eosinophils.ConclusionsThese data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.

Inhaled Corticosteroid-Containing Treatment Escalation and Outcomes for Patients with Asthma in a U.S. Health Care Organization.

Asthma is a common disorder that affects approximately 8% of the U.S. Treatment guidelines indicate inhaled corticosteroids (ICS) as the mainstay treatment, yet poor asthma control is common among ICS-treated patients. Treatment escalation (ICS dose increase and other controller therapy add-ons) is used to manage symptoms. Real-world studies of postescalation outcomes may inform treatment decisions. To (a) describe characteristics and treatment patterns among asthma patients who escalated treatment and (b) assess outcomes (exacerbations, uncontrolled asthma, and health care resource utilization [HCRU]) after escalation. The study cohort was identified from a large U.S. administrative claims database via ICD-9-CM codes for asthma (493.xx on ≥ 2 dates) and initiation (defining index date) of long-term (> 1 fill) ICS-containing treatment between January 1, 2009, and September 30, 2014. One year of continuous enrollment was required before and after the index date. Escalation was defined as ≥ 1 of the following: ICS dose increase; a switch between ICS, long-acting beta-2 agonists (LABA), or leukotriene modifiers (LTRM) to a different ICS, LABA, or LTRM; or add-on of controller medications (e.g., antibody biologic). Escalation patterns were examined. Rates of exacerbation (defined by inpatient admission, emergency department [ED] visit, or office visit with a pharmacy claim for an oral corticosteroid [OCS] within 7 days) and occurrence of uncontrolled asthma (defined by > 4 fills for a short-acting beta agonist [SABA] in a 1-year period, ≥ 1 OCS fill, or ≥ 1 asthma-related ED visit or inpatient admission) were calculated. Per-patient-per-year (PPPY) HCRU was estimated. Among 35,126 patients (mean [SD] age 38 [16] years) who initiated long-term ICS-containing treatment, 5,044 (14%) patients escalated their index regimens at 136 (105) days post-index (i.e., pre-escalation period). The most frequent changes, alone or in combination, included ICS dose increase (68%) or LABA (27%) or LTRM (25%) add-ons. Before escalation, the exacerbation rate was 1.60 (5.10) PPPY, and 1,108 (22%) patients experienced exacerbation. During the postescalation period of 251.6 (138.9) days, the exacerbation rate was 0.75 (2.9) PPPY, and 1,038 (21%) patients experienced exacerbation. A majority (> 85%) of exacerbations in the periods before and after escalation were associated with an office visit plus an OCS pharmacy claim within 7 days. Uncontrolled asthma was experienced by 41.5% and 41.0% of patients before and after escalation, respectively. Ambulatory care visits were common before (mean [SD] 24.0 [26.7] all-cause and 8.5 [13.4] asthma-related PPPY) and after escalation (19.3 [21.3] all-cause and 4.6 [8.1] asthma-related PPPY). Among asthma patients who initiated a long-term ICS-containing regimen, approximately 14% escalated therapy within a year of initiation. Yet, 21% of those patients had ≥ 1 exacerbation, and 41% of patients had uncontrolled asthma within 1 year after treatment escalation. The results demonstrate an unmet need among asthma patients who escalated their ICS-containing treatment. This study was sponsored and funded by Boehringer-Ingelheim, which contracted with Optum to conduct the research. The sponsor collaborated with Optum on the preparation, writing, revision, and approval of the manuscript. Bengston, Cao, Hulbert, Wolbeck, Elliott, and Buikema are employees of Optum. Yu and Wang are employed by Boehringer-Ingelheim. Study concept and design were contributed by Bengston, Yu, and Wang. Cao, Hulbert, and Wolbeck collected the data, and data analysis was performed by Bengston, Yu, and Wang. The manuscript was written by Bengston, along with Yu and Wang, and revised by Bengston, Yu, and Wang, along with the other authors.

Real-World Treatment Patterns Among Newly Diagnosed COPD Patients According to GOLD Airflow Limitation Severity Classification in a US Commercially Insured/Medicare Advantage Population

SESSION TITLE: COPD: Lessons for the Real-World Management of Disease SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: GOLD recommendations suggest the use of long acting β2 agonist (LABA) and/or long acting muscarinic antagonist (LAMA) for most COPD patients, reserving regimens containing inhaled corticosteroids (ICS) for a more severe subset of patients. Data on implementation of GOLD recommendations into clinical practice are limited. The purpose of this study was to characterize real-world treatment patterns among a spirometry-confirmed COPD population by GOLD airflow limitation severity classifications. METHODS: Over a study period of 1/1/2011 to 11/30/2015, a cohort of newly diagnosed COPD patients was identified using administrative claims from a large US payer. Patients were required to have ≥1 inpatient, ED or office visit claim for COPD from 1/1/2012 to 11/30/2013 and continuous health plan enrollment for 1 year prior to and 2 years after the first COPD diagnosis date. Patients with ≥1 claim for spirometry were eligible for medical record abstraction to confirm COPD diagnosis (FEV1/FVC ratio <0.7) and to determine GOLD 1-4 classification (based on post-bronchodilator FEV1 % predicted). Following COPD diagnosis, treatment patterns including COPD maintenance therapy (LAMA, LABA, ICS) observed and medication persistence (using a 60 day permissible gap) were evaluated for each GOLD classification. The rate of moderate/severe COPD exacerbation post-diagnosis was calculated. RESULTS: 85,247 newly diagnosed COPD patients were identified and 14,293 (17%) had a claim for spirometry use. Medical records containing complete spirometry results were obtained for 4,130 patients, with 1,505 (36%) having a spirometry-confirmed diagnosis. Among the 1,505 confirmed COPD patients, 333 (22%) were GOLD 1, 823 (55%) were GOLD 2, 317 (21%) were GOLD 3 and 32 (2%) were GOLD 4. Following COPD diagnosis, maintenance therapy was observed in 43% of GOLD 1, 56% of GOLD 2, 73% of GOLD 3 and 75% of GOLD 4 patients. GOLD 1 and 2 patients on maintenance therapy most frequently used ICS-LABA (48% & 45%, respectively), followed by LAMA only (29% for each) and ICS only (16% & 9%), while approximately 5% of GOLD 1 and 9% of GOLD 2 patients used triple therapy (ICS-LABA+LAMA). Similarly, a majority of GOLD 3 and 4 patients on maintenance therapy used ICS-LABA (37% & 42%), followed by LAMA only (28% & 25%) and triple therapy (20% & 17%). Overall, the observed maintenance therapy after diagnosis was an ICS-containing regimen for 67% of patients. Assessing persistence, mean (±SD) days on maintenance therapy was 143 days (±130), 188 days (±142), 215 days (±143) and 282 days (±132) for GOLD 1-4 and 191 days (±142) overall. Rates of severe/moderate COPD exacerbation per 100 person-years for GOLD 1-4 patients were 40.4, 48.9, 83.6 and 89.1, respectively. CONCLUSIONS: Large numbers of patients did not use maintenance therapy and the majority of those who did, across all GOLD classifications, used ICS-containing regimens (especially ICS-LABA), which is inconsistent with GOLD recommendations. Medication persistence was poor overall, especially in GOLD 1 patients. CLINICAL IMPLICATIONS: The observed inconsistencies with GOLD recommendations for COPD medication in this study highlight a gap between guidelines and clinical practice and the need for improved diagnosis and treatment of COPD patients. DISCLOSURE: Anna Wallace: Employee: I am an employee of HealthCore, a wholly owned subsidiary of Anthem, a health insurance company. I own Anthem stock. HealthCore received funding to conduct the work that led to this abstract. Valentina Zubek: Employee: Dr. Zubek reports she is an Employee of Boehringer Ingelheim. Shuchita Kaila: Employee: Dr. Kaila reports she is an Employee of Boehringer Ingelheim. Asif Shaikh: Employee: Dr. SHAIKH reports he is an Employee of Boehringer Ingelheim.reports other from Boehringer-Ingelheim, during the conduct of the study. Mayura Shinde: Employee: Dr. Shinde was an employee of HealthCore during the conduct of this work. HealthCore received funds from Boehrniger Ingelheim to conduct this work. Vincent Willey: Employee: Dr. Willey reports his employer, HealthCore, received funding from Boehringer Ingelheim to perform the study. Joseph Singer: Employee: Dr. Singer reports he is an employee and shareholder of HealthCore/Anthem. HealthCore received funds from Boehringer Ingelheim to conduct this work. The following authors have nothing to disclose: Mark Napier No Product/Research Disclosure Information

Potential Savings Achieved Through Switching COPD Patients from ICS-Containing Regimens to LAMA-LABA: A Dutch Perspective

Potential Savings Achieved Through Switching COPD Patients from ICS-Containing Regimens to LAMA-LABA: A Dutch Perspective

First maintenance therapy for COPD in the UK between 2009 and 2012: a retrospective database analysis.

Clinical guidelines recommend long-acting bronchodilators as first maintenance therapy for chronic obstructive pulmonary disease (COPD), with inhaled corticosteroids (ICS) reserved for patients with more severe disease and exacerbations. The aim of this analysis was to examine real-life prescribing of first maintenance therapy for COPD in the UK. Data were extracted from the UK Optimum Patient Care Research Database for patients with a first prescription for COPD maintenance therapy between 2009 and 2012 and a diagnosis of COPD at or before the date of the first prescription for COPD maintenance therapy. Routine clinical data including demographics, disease history and symptoms, comorbidities, therapy, hospitalisation rate and exacerbation rate were collected and used to characterise patients stratified by disease severity and Global Initiative for Chronic Obstructive Lung Disease (GOLD) group (A–D). The analysis population included 2,217 individuals (55.4% male, 45.2% smokers). Long-acting muscarinic antagonists (LAMA) as monotherapy were prescribed as first maintenance therapy for 40.2% of patients. ICS were prescribed as ICS/long-acting beta-agonists combination for 29.1% of patients or as monotherapy for 15.5%. ICS (alone or in combination) were prescribed to >40% of patients in each GOLD group. ICS-containing regimens were prescribed to patients with a history of pneumonia and comorbid conditions for whom the risks of ICS therapy may outweigh the benefits. The clinical reality of prescribing indicates that ICS are often prescribed outside current guideline recommendations for many patients newly diagnosed with COPD in the UK. Encouragingly, LAMAs are increasingly being prescribed as first maintenance therapy for these patients.

Changes in initial COPD treatment choice over time and factors influencing prescribing decisions in UK primary care: in UK primary care: a real-world, retrospective, observational.

Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines. This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD. Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis. Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997–2001; (2) 2002–2006; and (3) 2007–2010. Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression. The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment. Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis. Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors. In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens. Predictors of initial therapy were identified.

Respiratory Pharmacotherapy Use in Patients Newly Diagnosed with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in the UK: A Retrospective Cohort Study

This retrospective cohort study aimed to analyze the prescribing practices of general practitioners treating patients with newly diagnosed chronic obstructive pulmonary disease (COPD), and to assess characteristics associated with initial pharmacotherapy. Patients were identified in the General Practice Research Database, a population-based UK electronic medical record (EMR) with data from January 1, 2008 to December 31, 2009. Patient characteristics, prescribed COPD pharmacotherapies (≤12 months before diagnosis and within 3 months following diagnosis), co-morbidities, hospitalizations, and events indicative of a possible COPD exacerbation (≤12 months before diagnosis) were analyzed in 7881 patients with newly diagnosed COPD. Most patients (64.4%) were prescribed COPD pharmacotherapy in the 12 months before diagnosis. Following diagnosis, COPD pharmacotherapy was prescribed within 3 months in 85.0% of patients. Short-acting bronchodilators alone (22.9%) or inhaled corticosteroids + long-acting beta-2 agonists (ICS+LABA, 22.1%) were prescribed most frequently. Compared with other pharmacotherapies, the prevalence of severe airflow limitation was highest in patients prescribed ICS+LABA+long-acting muscarinic antagonists (LAMA). Moderate-to-severe dyspnea was identified most frequently in patients prescribed a LAMA-containing regimen. Patients prescribed an ICS-containing regimen had a higher prevalence of asthma or possible exacerbations recorded in the EMR than those not prescribed ICS. In conclusion, pharmacotherapy prescribed at initial COPD diagnosis varied by disease severity indicators as assessed by airflow limitation, dyspnea, history of asthma, and possible exacerbations. Frequent prescription of COPD pharmacotherapies before the first-recorded COPD diagnosis indicates a delay between obstructive lung disease presentation in primary care practice and assignment of a medical diagnosis.

Body mass index and phenotype in subjects with mild-to-moderate persistent asthma

Although obesity has been hypothesized to worsen asthma, data from studies of subjects with well-characterized asthma are lacking. We sought to evaluate the relationship between body mass index (BMI), asthma impairment, and response to therapy. BMI (in kilograms per meter squared) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies. One thousand two hundred sixty-five subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean versus overweight/obese asthmatic subjects demonstrated small differences in FEV1 (3.05 vs 2.91 L, P = .001), FEV1/forced vital capacity ratio (mean, 83.5% vs 82.4%; P = .01), rescue albuterol use (1.1 vs 1.2 puffs per day, P = .03), and asthma-related quality of life (5.77 vs 5.59, P = .0004). Overweight/obese asthmatic subjects demonstrated a smaller improvement in exhaled nitric oxide levels with inhaled corticosteroid (ICS) treatment than did lean asthmatic subjects (3.6 vs 6.5 ppb, P = .04). With ICS/long-acting beta-agonist treatment, overweight/obese asthmatic subjects demonstrated smaller improvements in lung function than lean asthmatic subjects, with an 80 mL (P = .04) and 1.7% (P = .02) lesser improvement in FEV1 and FEV1/forced vital capacity ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed. Increased BMI is not associated with clinically significant worsening of impairment in subjects with mild-to-moderate persistent asthma. There is a modest association between increased BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the effect of being overweight or obese on treatment response in asthma are warranted.

Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results

Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 microg, fluticasone propionate (FP) 500 microg, and the combination (SFC) with placebo in 6,184 patients with moderate-to-severe COPD over 3 yrs. Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatment-yrs, respectively). Risk factors for pneumonia were age > or =55 yrs, forced expiratory volume in 1 s <50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index <25 kg.m(-2). No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.