Dispensing of fluticasone propionate/salmeterol combination in the summer and asthma-related outcomes in the fall

doi:10.1016/j.jaci.2009.08.042

Journal of Allergy and Clinical Immunology

Volume 124, Issue 6, December 2009, Pages 1197-1203

https://doi.org/10.1016/j.jaci.2009.08.042 Get rights and content

Background

Asthma exacerbations occur year-round; however, peak asthma-related events occur in the fall and are frequently associated with viral respiratory infections.

Objective

To compare the rates of asthma-related emergency department (ED) visits and hospitalizations in the fall (September, October, November) between users and nonusers of fluticasone propionate plus salmeterol in a single inhaler (FSC) in the preceding summer.

Methods

This was a retrospective, observational study using health care claims from a large managed care database. Patients age 4 to 55 years with both a medical claim for asthma and a pharmacy claim for FSC were categorized into 3 age groups: children (4-11 years), adolescents (12-18 years), and adults (19-55 years).

Results

There were 201,973 observations of FSC dispensings and 184,143 observations without FSC. Across all age groups, summertime dispensings of FSC were associated with a significantly lower (P < .001) risk of an asthma-related ED visit (4-11 years: adjusted odds ratio [OR], 0.54, 95% CI, 0.49-0.60; 12-18 years: OR, 0.59, 95% CI, 0.54-0.64; 19-55 years: OR, 0.53, 95% CI, 0.51-0.55) or hospitalization (4-11 years: OR, 0.43, 95% CI, 0.35-0.54; 12-18 years: OR, 0.49, 95% CI, 0.40-0.60; 19-55 years: OR, 0.61, 95% CI, 0.57-0.65) in the subsequent fall. This protective effect persisted even for patients with fall dispensings of FSC. The risk of oral corticosteroid dispensing in the fall was also significantly reduced in all age groups.

Conclusion

Summertime dispensings of FSC were associated with a decreased risk of serious asthma-related outcomes in the subsequent fall. Continuous use of FSC before seasonal viral exposure may decrease seasonally related exacerbations.

Section snippets

Study design

This was a retrospective observational analysis using health care claims from December 1, 2002, to May 31, 2006, from a large managed care database that contains more than 45 US health plans representing 58.5 million covered lives. This proprietary, Health Insurance Portability Accountability Act–compliant research database contains integrated enrollment, laboratory, pharmacy, and medical claims data.

Study population

The study population consisted of patients age 4 to 55 years with both a medical diagnosis

Results

Overall, asthma-related events were greatest in the fall months throughout the entire study period (Fig 1). A comparison of baseline characteristics for patients with and without FSC dispensing during the summer is presented in Table I. A total of 386,116 observations were evaluated, including 201,973 observations of summertime FSC dispensing and 184,143 observations without FSC dispensed. Patients of all age groups who were dispensed FSC during the summer were more symptomatic during the

Discussion

The results of our longitudinal database claims analysis demonstrate that the dispensing of an anti-inflammatory such as FSC in the summer was associated with a reducing the risk of serious asthma-related exacerbations in the subsequent fall. Summertime dispensing of FSC had lower rates of asthma-related ED visits or hospitalization in the fall compared with the cohort without summertime possession of FSC. Pharmacy claims for OCS and SABA in the fall were also lower among patients dispensed FSC

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Les corticoïdes inhalés constituent la pierre angulaire du traitement de l’asthme. Les schémas de corticothérapie inhalés diffèrent sensiblement selon des différentes recommandations internationales mais reposent sur les principes de traitement continu et recherche de dose minimale efficace. Plusieurs études récentes semblent néanmoins démontrer l’intérêt potentiel de schémas discontinus chez le nourrisson comme chez l’enfant. Ces études ont été reprises dans le Global Initiative for Asthma (GINA) 2015 préscolaire qui positionne le traitement discontinu néanmoins en deuxième intention. Quelle lecture faire de ces études et comment adapter ou pas nos pratiques ?
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However, in other situations where adherence is not high, efforts to increase adherence have proven beneficial. For example, increasing use of medication in the summer months has been shown to be associated with reduced fall exacerbations.29 EPR-3 directed therapy can achieve excellent control of symptoms and reduce exacerbations in the majority of children with asthma in inner-city populations.
Asthma exacerbations are important components of asthma morbidity. The Inner-City Asthma Consortium was established in the early 1990s to identify risk factors for and to evaluate treatments to reduce asthma symptoms and exacerbations. Early studies identified atopy and inadequate treatment as important drivers of asthma morbidity. Later studies demonstrated that good adherence to guidelines-based asthma care could virtually eliminate symptoms and reduce but not eliminate exacerbations. Looking at exacerbations by season, risk factors were found to vary across the different seasons. Of the 7 factors identified, allergic status and pulmonary functions were found to be important for exacerbations in all seasons, but allergy had its strongest effect in the fall season. Therefore, additional therapy directed at reducing the role of allergy was evaluated and found to significantly reduce exacerbations even in participants with good symptom control when receiving guidelines-based therapy. Despite this year around aggressive therapy, exacerbations remain albeit at a lower level and with less seasonal variation. Another strategy, the short term use of therapy aimed at reducing the role of allergy begun before the fall season and focused on individuals at high risk for exacerbations, was found to be an effective approach to minimize exacerbations and to limit the amount of therapy necessary.
Adherence Monitoring and E-Health: How Clinicians and Researchers Can Use Technology to Promote Inhaler Adherence for Asthma
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Most EMD intervention studies to date have not been able to demonstrate changes in clinical asthma outcomes or have been unable to link improved adherence with better health outcomes.34 This may partly relate to the brevity of the interventions, differing asthma phenotypes that require differing treatment intensities,40 inappropriate prescribed doses, a potential lag of several months between poor adherence and negative asthma outcomes,41 “ceiling” or threshold effects in response to ICS,26 and the tendency for improved adherence in the lead up to an exacerbation.4 Population-based evidence tends to support the relationship between poor adherence and poorer asthma outcomes,3,5 but the current evidence from intervention studies remains weak.
In the past decade, rapid technological developments have advanced electronic monitoring devices (EMD) for asthma inhalers beyond simple recording of actuations to providing adherence promotion features and detailed information about patterns of medication use. This article describes currently available EMDs, discusses their utility and limitations in assessing adherence, and describes the potential for EMD-based adherence promotion interventions in clinical settings. To date, the main use of EMDs has been in clinical research. In selected populations, simple EMD-based adherence interventions, delivered either through clinician-to-patient feedback about medication use or by direct-to-patient reminders for missed doses, can significantly improve adherence. Further work is now needed to determine the impact of EMDs on clinical outcomes and their cost-effectiveness and feasibility for different clinical settings, including in disadvantaged populations. If this evidence can be provided, then the use of EMDs could expand into the management of asthma in populations with high health care costs, eg, severe asthma. In the future, medication monitoring could help distinguish poor treatment response from poor adherence, guide prescribing decisions, and prompt providers to discuss barriers to adherence; electronic health records may provide the gateway for integrating medication-use monitoring into digital chronic care management.
Objective airway monitoring improves asthma control in the cold and flu season: A cluster randomized trial
2010, Chest
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The improvement in asthma control for the intervention group can be explained by increased adherence to ICS medication during winter months. Others have described a relationship between decreased seasonal adherence and subsequent increases in asthma morbidity.18 Worsening peak flow values and trends during the winter season may have prompted brief improvements in adherence to ICS medication.
The goals of asthma care are reductions in risk and impairment, but achieving these goals requires collaborative work between patients and their clinicians. The purpose of this study was to improve inhaled corticosteroid (ICS) adherence and asthma control by cueing therapeutic communication between patients with asthma and their primary care clinicians.
We conducted a prospective, cluster-randomized, controlled effectiveness trial to assess the effect of providing visually standardized, interpreted peak flow graphs (CUE intervention) to patients and their clinicians on ICS adherence and asthma control. Asthma control outcomes were analyzed by season to account for seasonal variations in exacerbation frequency.
Although mean log-transformed ICS adherence was not significantly different between the two groups, there was a trend toward preserved adherence in the intervention group over time (P = .16). Intervention patients required fewer courses of oral steroids during winter (9% vs 23%, P < .001) and spring (3% and 17%, P < .001) compared with control subjects. Intervention patients also had fewer periods of worsening symptoms (65% vs 89%, P < .001) and fewer urgent care visits (10% vs 23%, P < .001) during winter compared with control subjects. Post hoc analysis showed significant improvement in the intervention group with respect to ICS adherence during winter months (P < .05), the likely explanation for the reduction in prednisone use and symptoms. Day-to-day peak flow variability in the intervention group fell consistently throughout the study from an average of 32% at baseline to 23% at final measurement (P < .001), indicating less airway reactivity over time.
Our findings provide evidence of the value of peak flow monitoring for patients with asthma during seasons of greatest vulnerability, the cold/flu season. The peak flow information apparently led to improvements in ICS adherence resulting in less need for prednisone rescue and fewer episodes of worsening symptoms.
ClinicalTrials.gov; No.: NCT00201188; URL: www.clinicaltrials.gov
Controller medications and their effects on asthma exacerbations temporally associated with upper respiratory infections
2010, Respiratory Medicine
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Furthermore, although the studies presented here were of varying durations and were heterogeneous in nature with respect to the run-in period, the results were consistent with between the datasets analyzed (GOAL and RCT) and were consistent with the results currently present in the literature regarding an association between a reduction of exacerbations and controller medication use. These results are further supported by a recent observational study that confirms the importance of the use of maintenance controller medication and supports the hypothesis that controller medication protects and preserves the epithelial integrity.53 Spahn et al. demonstrated that dispensing of controller medication during a season was associated with a decreased risk of asthma-related emergency department visits and hospitalizations in the subsequent season.
Exacerbations are a major risk and a cause of asthma morbidity and healthcare utilization. Viral-induced upper respiratory tract infections are the most frequent trigger of asthma-related exacerbations. Studies have traditionally assessed exacerbations without documentation regarding exacerbation etiology. Therefore, it remains unknown whether asthma medications can alter exacerbation susceptibility based on a specific etiology.
To examine whether treatment with inhaled corticosteroids plus long-acting beta₂-agonists reduced the number of exacerbations associated with upper respiratory tract infections versus inhaled corticosteroids alone.
Two large datasets comparing treatment with fluticasone propionate and fluticasone propionate plus salmeterol were analyzed, including the number of clinically reported upper respiratory tract infections, asthma-related exacerbations, and the presence of an exacerbation and concurrent report of an upper respiratory tract infection.
Both treatment groups had similar incidences of upper respiratory tract infections. Of those reporting an upper respiratory tract infection, statistically significantly fewer reported an asthma-related exacerbation comparing fluticasone propionate plus salmeterol with fluticasone propionate (p = 0.0057).
This retrospective analysis suggests that therapy with fluticasone propionate plus salmeterol provides protection against asthma exacerbations temporally associated with upper respiratory tract infections. This retrospective analysis supports the hypothesis that specific therapeutic approaches to mitigate virus-associated exacerbations may benefit asthma care. Well-controlled prospective studies are warranted.
A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma
2010, Journal of Allergy and Clinical Immunology
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Despite the low estimated levels of adherence, further decreases over the study period were associated with poor outcomes, suggesting that there was underuse of controller medication. In addition, seasonal variation in ICS use (ie, lower summertime use) could have accounted for the low baseline and follow-up adherence measures32; however, we do not anticipate that this would have affected the differences observed by level of physician viewing. Outcomes were analyzed as intention to treat and included individuals who neither had a primary care visit nor had their adherence information viewed during the study period.
Inhaled corticosteroid (ICS) nonadherence is common among patients with asthma; however, interventions to improve adherence have often been complex and not easily applied to large patient populations.
To assess the effect of supplying patient adherence information to primary care providers.
Patients and providers were members of a health system serving southeast Michigan. Providers (88 intervention; 105 control) and patients (1335 intervention; 1363 control) were randomized together by practice. Patients were age 5 to 56 years, had a diagnosis of asthma, and had existing prescriptions for ICS medication. Adherence was estimated by using prescription and fill data. Unlike clinicians in the control arm, intervention arm providers could view updated ICS adherence information on their patients via electronic prescription software, and further details on patient ICS use could be viewed by selecting that option. The primary outcome was ICS adherence in last 3 months of the study period.
At the study end for the intention-to-treat analysis, ICS adherence was not different among patients in the intervention arm compared with those in the control arm (21.3% vs 23.3%, respectively; P = .553). However, adherence was significantly higher among patients whose clinician elected to view their detailed adherence information (35.7%) compared with both control arm patients (P = .026) and intervention arm patients whose provider did not view adherence data (P = .002).
Overall, providing adherence information to clinicians did not improve ICS use among patients with asthma. However, patient use may improve when clinicians are sufficiently interested in adherence to view the details of this medication use.

View all citing articles on Scopus

: Supported by GlaxoSmithKline, Research Triangle Park, NC.

: Disclosure of potential conflict of interest: R. H. Stanford and D. A. Stempel are employees of GlaxoSmithKline. J. Spahn has received honoraria and served as a consultant for GlaxoSmithKline, has received research support from Merck, and has served as an expert witness for GlaxoSmithKline. K. Sheth has received honoraria from Alcon, AstraZeneca, and Sanofi; has served as a consultant for Sepracor (Altana); and has received honoraria and served as a consultant for GlaxoSmithKline. W.-S. Yeh has received consulting fees from GlaxoSmithKline.

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Asthma and lower airway diseaseDispensing of fluticasone propionate/salmeterol combination in the summer and asthma-related outcomes in the fall

Background

Objective

Methods

Results

Conclusion

Section snippets

Study design

Study population

Results

Discussion

Ann Allergy Asthma Immunol

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

The relationship of fall school opening and emergency department asthma visits in a large metropolitan area

Arch Pediatr Adolesc Med

Comparison of the seasonal patterns of asthma identified in general practitioner episodes, hospital admissions, and deaths

Thorax

Asthma and lower airway disease
Dispensing of fluticasone propionate/salmeterol combination in the summer and asthma-related outcomes in the fall