Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: A real-world observational study

doi:10.1016/j.jaci.2010.06.040

Journal of Allergy and Clinical Immunology

Volume 126, Issue 3, September 2010, Pages 511-518.e10

https://doi.org/10.1016/j.jaci.2010.06.040 Get rights and content

Background

Long-term randomized trials comparing asthma outcomes between inhaled corticosteroids in real-world populations are lacking. As such, rigorously conducted observational studies to complement the findings of randomized trials are needed.

Objective

We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care database for patients aged 5 to 60 years receiving a first prescription (initiation population) or dose increase (step-up population) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone.

Methods

We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures. Coprimary outcomes were asthma control (a composite measure comprising no unplanned visit or hospitalization for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and exacerbation rate.

Results

More than 80% of patients in each population achieved asthma control; 10% and 16% of patients in the initiation and step-up populations, respectively, received add-on or combination therapy during the year. Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both populations (P ≤ .001). In the initiation population (n = 1319 in each cohort) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 (95% CI, 1.02-1.65) relative to fluticasone. In the step-up population (cohorts: n = 250) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 (95% CI, 0.66-2.26). Exacerbation rates were similar between cohorts.

Conclusions

In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone.

Section snippets

Data source

The General Practice Research Database (GPRD) is a large, well-maintained database administered as a not-for-profit by the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency that contains deidentified longitudinal medical records from approximately 500 primary care practices in the UK.16, 17, 18 Patients' records in the GPRD total 13 million, and active records number 3.6 million, which is equivalent to 5.5% of the UK population. The demographic characteristics of patients

Results

A first prescription of HFA-beclomethasone or fluticasone administered by means of an MDI was issued for 4411 patients; of these, 2638 were matched, resulting in 1319 patients in each treatment cohort of the initiation population. The median length of time patients were registered in the GPRD without a prior ICS prescription was 9.4 years (interquartile range, 5.1-15.4 years) for the HFA-beclomethasone cohort and 7.8 years (interquartile range, 4.6-13.0) for the fluticasone cohort.

Of 1,170

Discussion

In this analysis of real-world asthma management in primary care, initiating treatment with either HFA-beclomethasone or fluticasone effectively improved asthma control, as per the predefined composite measures. In patients already taking ICSs and requiring a step-up in treatment, increasing the dose of either HFA-beclomethasone or fluticasone effectively reestablished asthma control. These real-world results reinforce guideline recommendations to start with ICS monotherapy and then step up, as

References (40)

K. Herland et al.
How representative are clinical study patients with asthma or COPD for a larger “real life” population of patients with obstructive lung disease?
Respir Med
(2005)
C.L. Leach et al.
Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers
Chest
(2002)
M. Aubier et al.
Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 μg day-1) versus HFA-fluticasone propionate (1000 μg day-1) in patients with asthma
Respir Med
(2001)
A. Fairfax et al.
A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate
Ann Allergy Asthma Immunol
(2001)
M.E. Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)
R.A. Pauwels et al.
Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial
Lancet
(2003)
A. Sindi et al.
Antiinflammatory effects of long-acting beta2-agonists in patients with asthma: a systematic review and metaanalysis
Chest
(2009)
P.G. Gibson et al.
Differential effects of maintenance long-acting beta-agonist and inhaled corticosteroid on asthma control and asthma exacerbations
J Allergy Clin Immunol
(2007)
J.C. Virchow et al.
Importance of inhaler devices in the management of airway disease
Respir Med
(2008)
S. Verbanck et al.
The functional benefit of anti-inflammatory aerosols in the lung periphery
J Allergy Clin Immunol
(2006)

M. Yamaguchi et al.

Effect of inhaled corticosteroids on small airways in asthma: investigation using impulse oscillometry

Pulm Pharmacol Ther

(2009)

R.J. Martin

Therapeutic significance of distal airway inflammation in asthma

J Allergy Clin Immunol

(2002)

Expert panel report 3: guidelines for the diagnosis and management of asthma. National Asthma Education and Prevention...

British guideline on the management of asthma, May 2008, revised June 2009. British Thoracic Society, Scottish...

Global Strategy for Asthma Management and Prevention, updated 2009. Global Initiative for Asthma (GINA); 2009....

C.H. Fanta

Asthma. N Engl J Med

(2009)

J. Shepherd et al.

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Health Technol Assess

(2008)

J. Travers et al.

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

Thorax

(2007)

K. Benson et al.

A comparison of observational studies and randomized, controlled trials

N Engl J Med

(2000)

J. Concato et al.

Randomized, controlled trials, observational studies, and the hierarchy of research designs

N Engl J Med

(2000)

Cited by (68)

Smoking cessation in asthmatic patients and its impact
2021, Revue des Maladies Respiratoires
La prévalence du tabagisme chez les patients asthmatiques est identique ou plus élevée qu’en population générale.
Cette revue systématique étudie les conséquences du tabagisme sur l’asthme, les stratégies de sevrage tabagique (ST) chez l’asthmatique et les conséquences du ST sur l’asthme.
Le tabagisme actif ou passif peut favoriser le développement de l’asthme et a des nombreux effets délétères sur l’asthme. Les rares études sur le ST chez les fumeurs asthmatiques montrent l’efficacité des stratégies classiques du ST chez ces patients (substituts nicotiniques, varénicline, bupropion, thérapies cognitives et comportementales). L’arrêt du tabagisme des parents ayant des enfants asthmatiques est essentiel et repose sur les mêmes stratégies. La cigarette électronique peut être une aide utile à l’arrêt du tabac chez certains patients. L’arrêt du tabagisme est bénéfique chez les fumeurs asthmatiques : réduction des symptômes, des exacerbations aiguës, de l’hyperréactivité bronchique et de l’inflammation bronchique ; diminution du recours aux médicaments d’urgence et des doses de corticostéroïdes inhalés ; amélioration du contrôle de l’asthme, de la qualité de vie et de la fonction respiratoire.
Chez les patients asthmatiques, il est essentiel d’évaluer le statut tabagique et les professionnels de santé doivent les aider à arrêter de fumer.
The prevalence of smoking in asthmatic patients is similar to, or even higher than in the general population.
This systematic review addresses (1) the effects of smoking on asthma, (2) smoking cessation strategies in asthmatic patients, and (3) the consequences of smoking cessation for people with asthma.
Active or passive smoking can promote the development of asthma. The few studies on smoking cessation in asthma confirm the efficacy of validated smoking cessation strategies in these patients (nicotine replacement therapy, varenicline, bupropion, cognitive and behavioural therapies). Smoking cessation in parents with asthmatic children is essential and is based on the same strategies. Electronic cigarettes may be a useful help to quit smoking in some patients. Smoking cessation is beneficial in asthmatic smokers and associated with (1) a reduction of asthma symptoms, acute exacerbations, bronchial hyperresponsiveness, and bronchial inflammation, (2) decreased use of rescue medications and in doses of inhaled corticosteroids, (3) improved asthma control, quality of life, and lung function.
In asthmatic patients, it is essential to assess smoking status and health professionals must assist them to quit smoking.
Management/Comorbidities of School-Aged Children with Asthma
2019, Immunology and Allergy Clinics of North America
45 - Wheezing in Older Children: Asthma
2019, Kendig's Disorders of the Respiratory Tract in Children
Asthma is the most common cause of wheezing in school age children and adolescents. An inflammatory condition characterized by variable, reversible airway obstruction and hyperreactivity, asthma is a complex, heterogeneous disorder with numerous phenotypes. The pathophysiology, genetics, natural history, and response to treatment vary widely among these phenotypes. Characteristic symptoms—wheezing, cough, and chest tightness—may be precipitated by a variety of triggers including allergens, exercise, infection, weather change, and emotion. Diagnosis is based on history, symptom report, and detection of reversible airflow obstruction using objective measures of lung function. Disease management is focused on control rather than severity. Asthma controller medications include antiinflammatory agents (e.g., inhaled corticosteroids, leukotriene modifiers), long-acting beta-agonists, and long-acting muscarinic antagonists. Short-acting beta-adrenergic agonists (e.g., albuterol) are required for symptom relief. Trigger avoidance, environmental controls, frequent monitoring of symptoms and treatment response, periodic assessment of pulmonary function, and effective patient-physician partnership are also critical to successful asthma management. Asthma exacerbations in children may be mild and respond quickly to home administration of short-acting bronchodilators but can also rapidly progress into a medical emergency. Any asthma exacerbation that fails to respond to home management should be assessed and treated in an acute care facility or physician's office. Short-acting beta agonists and systemic corticosteroids are the mainstay of therapy for acute episodes. Severe exacerbations should be treated in a hospital setting with inhaled anticholinergic medications, intravenous magnesium sulfate, supplemental oxygen, subcutaneous epinephrine, and, in extreme cases, mechanical ventilation.
Initiating or changing to a fixed-dose combination of Fluticasone propionate/Formoterol over Fluticasone propionate/Salmeterol: A real-life effectiveness and cost impact evaluation
2017, Respiratory Medicine
Asthma has a substantial impact on quality of life and health care resources. The identification of a more cost-effective, yet equally efficacious, treatment could positively influence the economic burden of this disease. Fluticasone propionate/Formoterol (FP/FOR) may be as effective as Fluticasone Salmeterol (FP/SAL). We evaluated non-inferiority of asthma control in terms of the proportion of patients free from exacerbations, and conducted a cost impact analysis.
This historical, matched cohort database study evaluated two treatment groups in the Optimum Patient Care Research Database in the UK: 1) an FP/FOR cohort of patients initiating treatment with FP/FOR or changing from FP/SAL to FP/FOR and; 2) an FP/SAL cohort comprising patients initiating, or remaining on FP/SAL pMDI combination therapy. The main outcome evaluated non-inferiority of effectiveness (defined as prevention of severe exacerbations, lower limit of the 95% confidence interval (CI) of the mean difference between groups in patient proportions with no exacerbations is −3.5% or higher) in patients treated with FP/FOR versus FP/SAL.
After matching 1:3, we studied a total of 2472 patients: 618 in the FP/FOR cohort (174 patients initiated on FP/FOR and 444 patients changed to FP/FOR) and 1854 in the FP/SAL cohort (522 patients initiated FP/SAL and 1332 continued FP/SAL). The percentage of patients prescribed FP/FOR met non-inferiority as the adjusted mean difference in proportion of no severe exacerbations (95%CI) was 0.008 (−0.032, 0.047) between the two cohorts. No other significant differences were observed except acute respiratory event rates, which were lower for patients prescribed FP/FOR (rate ratio [RR] 0.82, 95% CI 0.71, 0.94).
Changing to, or initiating FP/FOR combination therapy, is associated with a non-inferior proportion of patients who are severe exacerbation-free at a lower average annual cost compared with continuing or initiating treatment with FP/SAL.
Real-Life Outcomes for Patients with Asthma Prescribed Spacers for Use with Either Extrafine- or Fine-Particle Inhaled Corticosteroids
2017, Journal of Allergy and Clinical Immunology: In Practice
Spacers are often used with pressurized metered-dose inhalers (pMDIs) to eliminate the need for coordinating inhalation with actuation.
To investigate the real-life effectiveness of spacers prescribed for use with either extrafine- or fine-particle inhaled corticosteroids (ICSs).
This historical matched cohort study examined anonymous medical record data over 2 years (1-year baseline, 1-year outcome) for patients with asthma aged 12 to 80 years initiating ICSs by pMDI with or without prescribed spacer. We compared outcomes for spacer versus no-spacer arms, matched for key baseline and asthma-related characteristics, within 2 ICS cohorts: (1) extrafine-particle ICS (beclomethasone) and (2) fine-particle ICS (fluticasone). Effectiveness end points were compared using conditional regression methods.
Matched spacer and no-spacer arms of the extrafine-particle ICS cohort each included 2090 patients (69% females; median age, 46-47 years) and the 2 arms of the fine-particle ICS cohort each included 444 patients (67% females; median age, 45 years). With extrafine-particle ICS, we observed no significant difference between spacer and no-spacer arms in severe exacerbation rate (primary end point): adjusted rate ratio, 1.01 (95% CI, 0.83-1.23). With fine-particle ICS, the severe exacerbation rate ratio with spacers was 0.77 (0.47-1.25). Oropharyngeal candidiasis incidence was low and similar in spacer and no-spacer arms for both ICS cohorts.
We found no evidence that prescribed spacer devices are associated with improved asthma outcomes for extrafine- or fine-particle ICS administered by pMDI. These findings challenge long-standing assumptions that spacers should improve pMDI effectiveness and indicate the need for pragmatic trials of spacers in clinical practice.
Small airways disease and severe asthma
2017, World Allergy Organization Journal
The small airways of the lungs are commonly affected in pediatric and adult asthma. Small airways disease has been related to asthma control, severity, and risk of exacerbation. Diagnosis of small airways disease can be best made through evaluation of surgical lung specimens. Noninvasive techniques including spirometry, plethysmography, nitrogen washout, impulse oscillometry, and cross-sectional imaging have been utilized to assess and infer the extent of small airways disease in asthma and can be used longitudinally to assess response to treatment. Patients with small airways disease seem to benefit from inhaled asthma medications that have improved capacity to reach the distal lung compartment. This is especially important for patients with severe asthma, who rely upon high doses of inhaled corticosteroid and bronchodilators for asthma control. This review will describe the techniques which may be utilized to assess small airways disease, discuss the prevalence and characteristics of small airways disease in severe asthma, and highlight how small airway disease may complicate severe asthma treatment.

View all citing articles on Scopus

: Access to data from the General Practice Research Database was funded by Merck & Co, Inc, and the analysis was funded by Teva Pharmaceuticals Limited.

: Disclosure of potential conflict of interest: D. Price is a consultant for Aerocrine, Boehringer Ingelheim, Dey Pharmaceuticals, GlaxoSmithKline, Merck, Merck Generics, Sharpe and Dohme, Novartis, Schering-Plough, Teva, Bayer (antibiotic study design); has spoken at meetings sponsored by Boehringer Ingelheim, GlaxoSmithKline, Merck, Sharpe and Dohme, Pfizer, Schering-Plough, Altana Pharma, and Chiesi; has received research support from UK National Health Centre, Aerocrine, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck, Sharpe and Dohme, Novartis, Pfizer, Schering-Plough, and Teva. R. J. Martin is a lecturer and consultant for Teva; is a consultant for AstraZeneca, Novartis/Genentech, Schering, Cypress BioScience, Phase to Phase and Common Health, and the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH); and has received research support from the NHLBI/NIH. N. Barnes has provided lectured consultancy for GlaxoSmithKline, AstraZeneca, Chiesi, Boehringer, Teva, and Nycomed and has received research support from GlaxoSmithKline, Novartis, and Schering-Plough. E. Israel is a consultant for Abbott, Amgen, Cowen & Co, GlaxoSmithKline, Icagen, MedImmune, Merck, NewMentor, NKT Therapeutics, Ono Pharmaceuticals US, Pulmatrix, Schering-Plough, and Teva Specialty Pharmaceuticals and has received research support from Aerovance, Amgen, Ception Therapeutics, Genentech, Icagen, Johnson & Johnson, MedImmune, National Institutes of Health, and Novartis. E. V. Hillyer has done freelance writing for Merck, Aerocrine, and Teva Sante (France). G. Colice has served as a consultant/speaker for Teva, Dey, BT, GlaxoSmithKline, Vakera, Skye Pharma, and MedImmune and has served as an expert witness on the topic of long-acting β-agonists. The rest of the authors have declared that they have no conflict of interest.

View full text

Asthma and lower airway diseasePrescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: A real-world observational study

Background

Objective

Methods

Results

Conclusions

Section snippets

Data source

Results

Discussion

Respir Med

Chest

Respir Med

Ann Allergy Asthma Immunol

J Chronic Dis

Lancet

Chest

J Allergy Clin Immunol

Respir Med

J Allergy Clin Immunol

Pulm Pharmacol Ther

J Allergy Clin Immunol

Asthma. N Engl J Med

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Health Technol Assess

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

Thorax

A comparison of observational studies and randomized, controlled trials

N Engl J Med

Randomized, controlled trials, observational studies, and the hierarchy of research designs

N Engl J Med

Asthma and lower airway disease
Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: A real-world observational study