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Meta-Analysis
. 2011 Dec 7;2011(12):CD004106.
doi: 10.1002/14651858.CD004106.pub4.

Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children

Toby J Lasserson  1 , Giovanni Ferrara, Lucio Casali
Affiliations
Meta-Analysis

Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children

Toby J Lasserson et al. Cochrane Database Syst Rev. .

Abstract

Background: Long-acting beta-agonists are a common second line treatment in people with asthma inadequately controlled with inhaled corticosteroids. Single device inhalers combine a long-acting beta-agonist with an inhaled steroid delivering both drugs as a maintenance treatment regimen. This updated review compares two fixed-dose options, fluticasone/salmeterol FP/SALand budesonide/formoterol, since this comparison represents a common therapeutic choice.

Objectives: To assess the relative effects of fluticasone/salmeterol and budesonide/formoterol in people with asthma.

Search methods: We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Search results are current to June 2011.

Selection criteria: We included randomised studies comparing fixed dose fluticasone/salmeterol and budesonide/formoterol in adults or children with a diagnosis of asthma. Treatment in the studies had to last for a minimum of 12 weeks.

Data collection and analysis: Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Main results: Five studies met the review entry criteria (5537 adults). Study populations entered the studies having previously been treated with inhaled steroids and had moderate or mild airway obstruction (mean FEV(1) predicted between 65% and 84% at baseline). Most of the studies assessed treatment over a period of six months. The studies were at a low risk of selection and performance/detection bias, although we could not determine whether missing data had an impact on the results. Availablility of outcome data was satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral steroids was lower with fluticasone/salmeterol but did not reach statistical significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N = 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants requiring oral steroids, treatment with fluticasone/salmeterol would lead to between 25 fewer and seven more people per 1000 experiencing a course of oral steroids. Although the odds of hospital admission was higher with fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95% CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000 would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse event related to asthma was higher with fluticasone/salmeterol but did not differ significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies, 4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 13 more people per 1000 would experience a serious adverse event on fluticasone/salmeterol.Secondary outcomesLung function outcomes, symptoms, rescue medication, composite of exacerbations leading to either emergency department visit or hospital admission, withdrawals and adverse events did not differ statistically between treatments. Assessment of quality of life was limited to two studies, both of which gave results that did not reach statistical significance. One study reported one death out of 1000 participants on fluticasone/salmeterol and no deaths in a similar number of participants treated with budesonide/formoterol. No deaths were reported in the other studies.

Authors' conclusions: Statistical imprecision in the effect estimates for exacerbations and serious adverse events do not enable us to conclude that either therapy is superior. The uncertainty around the effect estimates justify further trials to provide more definitive conclusions; the overall quality of evidence based on GRADE recommendations for the three primary outcomes and withdrawals due to serious adverse events was moderate. We rated the quality of evidence for mortality to be low. Results for lung function outcomes showed that the drugs were sufficiently similar that further research is unlikely to change the effects. No trials were identified in the under-12s and research in this population is a high priority. Evaluation of quality of life is a priority for future research.

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Conflict of interest statement

There are no known conflicts of interest.

Figures

1
1
Study flow diagram. This represents the results of all literature searches up to June 2011.
2
2
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Combination fluticasone/salmeterol versus budesonide/formoterol, outcome: 1.1 Participants experiencing exacerbations requiring oral steroid treatment.
4
4
Forest plot of comparison: 1 Combination fluticasone/salmeterol versus budesonide/formoterol, outcome: 1.2 Participants experiencing exacerbations requiring admission to hospital.
5
5
Forest plot of comparison: 1 Combination fluticasone/salmeterol versus budesonide/formoterol, outcome: 1.3 Asthma‐related serious adverse event.
1.1
1.1. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 1 Participants experiencing exacerbations requiring oral steroid treatment.
1.2
1.2. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 2 Participants experiencing exacerbations requiring admission to hospital.
1.3
1.3. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 3 Asthma‐related serious adverse event.
1.4
1.4. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 4 Participants experiencing exacerbations requiring ED visit/hospitalisation.
1.5
1.5. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 5 Mortality.
1.6
1.6. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 6 Asthma Quality of Life Questionnaire.
1.7
1.7. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 7 N with improvement in Asthma Quality of Life Questionnaire.
1.8
1.8. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 8 Change in am PEF.
1.9
1.9. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 9 Change in pm PEF.
1.10
1.10. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 10 Change in FEV1.
1.11
1.11. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 11 Change in FEV1 predicted (%).
1.12
1.12. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 12 Change in rescue medication use.
1.13
1.13. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 13 Change in daytime symptoms.
1.14
1.14. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 14 Change in symptom‐free days.
1.15
1.15. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 15 Change in nocturnal awakenings.
1.16
1.16. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 16 Adverse events.
1.17
1.17. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 17 Headache.
1.18
1.18. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 18 Candidiasis.
1.19
1.19. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 19 Upper respiratory tract infection.
1.20
1.20. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 20 Dysphonia.
1.21
1.21. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 21 Rhinitis.
1.22
1.22. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 22 Throat irritation.
1.23
1.23. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 23 Cough.
1.24
1.24. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 24 Tremor.
1.25
1.25. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 25 Withdrawals.
1.26
1.26. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 26 Withdrawals (adverse events).
1.27
1.27. Analysis
Comparison 1 Combination fluticasone/salmeterol versus budesonide/formoterol, Outcome 27 Withdrawals (lack of efficacy).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Aalbers 2004 {published and unpublished data}
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    1. Astrazenca (SD‐039‐0686). A randomized, double‐dummy, double‐blind/open, parallel‐group, phase‐III, multicentre, 7‐month study to assess the efficacy and safety of Symbicort® Turbuhaler® (budesonide/formoterol; 160/4.5 mcg delivered dose) given either as standard therapy (2 inhalations bid) or with an adjustable dosing regimen (1, 2 or 4 inhalations bid) versus Seretide™ Diskus™ (salmeterol/fluticasone; 50/250 mcg metered dose) given as standard therapy (1 inhalation bid) in adult and adolescent asthmatic patients. http://www.astrazenecaclinicaltrials.com/Article/512577.aspx (accessed 19 October 2007).
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    1. AstraZeneca (D5896C00005). A two‐stage randomized, open‐label, parallel group, phase III, multicenter, 7 month study to assess the efficacy and safety of Symbicort pMDI administered either as fixed or as an adjustable regimen versus a fixed regimen of Advair in subjects 12 years of age and older with asthma. http://www.astrazenecaclinicaltrials.com (accessed 13 March 2008).
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    1. Busse WW, Shah SR, Somerville L, Martin P, Goldman M. Comparison of asthma exacerbations and lung function with adjustable‐dose Budesonide/Formoterol pressurized metered‐dose inhaler (BUD/FM pMDI), fixed‐dose BUD/FM pMDI, and fixed‐dose Fluticasone/Salmeterol dry powder inhaler (FP/SM DPI). http://www.abstracts2view.com/ats07 (accessed 13 March 2008).
COMPASS {published and unpublished data}
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    1. AstraZeneca (SD‐039‐0735). Comparison of the efficacy and safety of one inhalation of Symbicort® Turbuhaler® 160/4.5 µg bid plus as‐needed with two inhalations of SeretideTM EvohalerTM 25/125 µg bid plus Terbutaline Turbuhaler® 0.4 mg as‐needed, and one inhalation of Symbicort® Turbuhaler® 320/9 µg bid plus Terbutaline Turbuhaler® 0.4 mg as‐needed. A 6‐month, randomised, double‐blind, double‐dummy, parallel‐group, active‐controlled, multicentre, phase IIIB study in adult and adolescent asthmatic patients. http://www.astrazenecaclinicaltrials.com (accessed 2009).
    1. Bleecker ER, Postma DS, Lawrance R, Meyers DA, Ambrose H, Goldman M. Effect of polymorphisms in the beta2‐adrenergic receptor gene (ADRB2) on response to long‐acting beta2‐agonist (LABA) therapy. Journal of Allergy and Clinical Immunology 2007;119(2):523.
    1. Boonsawat W. Cost‐effectiveness of budesonide/formoterol maintenance and rescue therapy in Thailand. Asian Biomedicine 2010;4(4):571‐8.
    1. Buhl R, Kuna P. Does the choice of ICS/LABA regimen influence exacerbation rates in asthma patients with high as needed use?. European Respiratory Journal 2007;30(Suppl 51):617s.
EXCEL {published and unpublished data}
    1. Dahl OR, Chuchalin A, Lindberg A, Jones M, Aggarwal K, Gor D. EXCEL regular maintenance therapy with salmeterol/fluticasone propionate combination (SFC) reduces exacerbations more effectively than the formoterol/budesonide combination (FBC). European Respiratory Journal 2004;24(Suppl 48):309s.
    1. Dahl R, Chuchalin A, Gor D, Yoxall S, Sharma R. EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma. Respiratory Medicine 2006;100(7):1152‐62. - PubMed
    1. Dahl R, Chuchalin A, Ringdal N, Gor D, Jones M. Salmeterol/fluticasone (SFC) reduces moderate/severe exacerbations more effectively than formoterol/budesonide 9FBC) with sustained maintenance therapy EXCEL. American Thoracic Society International Conference; May 20‐25; San Diego, California. 2005:Poster: F68.
    1. GlaxoSmithKline (SAM40040). A twenty‐four week, randomised, double‐dummy, double‐blind, parallel group study to compare the rate of asthma exacerbations between SERETIDE DISKUS 50/250 µg 1 inhalation bd and formoterol/budesonide breath‐actuated dry powder inhaler (BADPI) 4.5/160 µg 2 inhalations bd in subjects with moderate to severe asthma. http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/IV_SAM40040.pdf (accessed 19 October 2007).
SAM40048 {unpublished data only}
    1. GlaxoSmithKline (SAM40048). Randomised, double‐blind, parallel group study on the efficacy and tolerability of the salmeterol 50 mcg/fluticasone 250 mcg combination Diskus compared to the formoterol 6mcg/budesonide 200 mcg combination turbohaler administered twice daily in patients with moderate bronchial asthma. http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/IV_SAM40048.pdf (accessed 19 October 2007).

References to studies excluded from this review

Adachi 2008 {published data only}
    1. Adachi M, Aizawa H, Ishihara K, Ohta K, Sano Y, Taniguchi H, et al. Comparison of salmeterol/fluticasone propionate (FP) combination with FP+sustained release theophylline in moderate asthma patients. Respiratory Medicine 2008;102(7):1055‐64. - PubMed
AHEAD {published data only}
    1. AstraZeneca. Efficacy and safety of Symbicort ® Turbuhaler® 160/4.5 µg/inhalation, two inhalations twice daily plus as‐needed compared with Seretide™ Diskus™ 50/500 µg/inhalation, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as‐needed ‐ a 6‐month, randomised, double‐blind, parallel‐group, active controlled, multinational phase IIIB study in adult and adolescent patients with persistent asthma (AHEAD). www.clinicaltrials.gov (accessed 2005).
    1. AstraZeneca (D5890C00002). Efficacy and safety of Symbicort® Turbuhaler® 160/4.5 mcg/inhalation, two inhalations twice daily plus as‐needed compared with Seretide Diskus 50/500 mcg/inhalation, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as‐needed ‐ a 6‐month, randomised, double‐blind, parallel‐group, active controlled, multinational phase IIIB study in adult and adolescent patients with persistent asthma. http://www.astrazenecaclinicaltrials.com (accessed 12 May 2008).
    1. Bousquet J, Boulet L‐P. Budesonide/formoterol as maintenance and reliever therapy in uncontrolled asthma compared with high dose salmeterol/fluticasone: the AHEAD double blind study. European Respiratory Journal 2007;30(Suppl 51):358s.
    1. Bousquet J, Boulet L‐P, Peters MJ, Magnussen H, Quiralte J, Martinez‐Aguilar NE, et al. Budesonide/formoterol for maintenance and relief in uncontrolled asthma versus high‐dose salmeterol/fluticasone. Respiratory Medicine 2007;101(12):2437‐46. - PubMed
    1. Bousquet J, Miravitlles M, Wiren A. Budesonide/formoterol provides better efficacy at a lower or similar cost as compared to high dose salmeterol fluticasone treatment. European Respiratory Journal 2007;30(Suppl 51):193s.
ALLIANCE {published data only}
    1. Molimard M, Gros V, Bourdeix I. Efficacy of formoterol and beclomethasone dry powder capsules in asthmatic patients sub‐optimally controlled with fixed combination formoterol‐budesonide ALLIANCE study. European Respiratory Journal 2004;24(Suppl 48):261s.
Ambrose 2007 {published data only}
    1. Ambrose H, Lawrance R, Goldman M. Beta‐adrenergic receptor gly16arg variation: effect on response to budesonide/formoterol or budesonide (post‐formoterol) in asthma patient. Chest 2007;132(4):436a.
Bleecker 2007 {published data only}
    1. Bleecker E, Yancey S, Ortega H, Anderson W. Arginine 16 genotype does not modulate clinical response to salmeterol in subjects with asthma. Chest 2007;132(4):436.
Bodzenta‐Lukaszyk 2010a {published data only}
    1. Bodzenta‐Lukaszyk A, Dymek A, Mansikka H. Fluticasone propionate/formoterol fumarate combination therapy has a more rapid onset of action than fluticasone propionate/salmeterol xinafoate in the treatment of asthma: a randomised controlled trial. Thorax 2010;65:P24.
    1. Bodzenta‐Lukaszyk A, Dymek A, Mansikka H. Fluticasone propionate/formoterol fumarate combination therapy is as effective as fluticasone propionate/salmeterol xinafoate in the treatment of asthma: a randomised controlled trial. Thorax 2010;65:P177.
    1. Bodzenta‐Lukaszyk A, Dymek A, Mansikka H. Fluticasone propionate/formoterol fumarate combination therapy is as effective as fluticasone propionate/salmeterol xinafoate, but has a more rapid onset of action in the treatment of asthma. Thorax. 2010:P1205.
Bodzenta‐Lukaszyk 2010b {published data only}
    1. Bodzenta‐Lukaszyk A, Pulka G, Dymek A, Mansikka H. Fluticasone propionate/formoterol fumarate combination therapy has an efficacy and safety profile similar to that of its individual components administered concurrently in the treatment of asthma. European Respiratory Journal. 2010:P1207.
Bodzenta‐Lukaszyk 2011 {published data only}
    1. Bodzenta‐Lukaszyk A, Pulka G, Dymek A, Bumbacea D, McIver T, Schwab B, et al. Efficacy and safety of fluticasone and formoterol in a single pressurized metered dose inhaler. Respiratory Medicine 2011; Vol. 105:674‐82. - PubMed
Brambilla 2003 {published data only}
    1. Brambilla C, Gros V, Bourdeix I, Efficacy of Foradil in Asthma (EFORA) French Study Group. Formoterol 12 microg BID administered via single‐dose dry powder inhaler in adults with asthma suboptimally controlled with salmeterol or on‐demand salbutamol: a multicenter, randomized, open‐label, parallel‐group study. Clinical Therapeutics 2003;25(7):2022‐36. - PubMed
CONCEPT {published data only}
    1. FitzGerald JM, Boulet LP, Follows RMA. The CONCEPT trial: A 1‐year, multicenter, randomized, double‐blind, double‐dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/ budesonide in adults with persistent asthma. Clinical Therapeutics 2005;27(4):393‐406. - PubMed
    1. Fitzgerald JM, Boulet LP, Follows R. Improved control of symptoms, exacerbations and quality of life with stable dose treatment with salmeterol/fluticasone (SFC) compared with adjustable maintenance dosing with formoterol/budesonide. XIX World Allergy Organization Congress, June 26‐July 1, Munich, Germany. 2005:Abstract 289.
    1. Fitzgerald M, Boulet LP, Pieters WR. Improved control of symptoms and exacerbations with stable dose treatment with salmeterol/fluticasone propionate (SFC) compared with adjustable maintenance dosing with formoterol/budesonide (FBC). European Respiratory Journal 2005; Vol. 26, issue Suppl 49:Abstract No. 2765.
    1. GlaxoSmithKline (SAM40056). A randomised, double‐blind, double‐dummy, 52 week, parallel group study of a standard dosing regimen with salmeterol/fluticasone combination 50/250mcg bid (via the DISKUS/ACCUHALER inhaler) versus a symptom‐driven, variable dosing regimen with formoterol/budesonide combination 6/200mcg (via a breath‐actuated dry powder reservoir inhaler) in adult asthmatics. http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/IV_SAM40056.pdf (accessed 19 October 2007).
    1. Price DB, Williams AE, Yoxall S. Salmeterol/fluticasone stable‐dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health‐related quality of life. Respiratory Research 2007;8:46. - PMC - PubMed
Creemers 2002 {published data only}
    1. Creemers JP, Bantje T, Eliraz A, Ekstrom T, Buhl R. Budesonide/formoterol in a single inhaler once or twice daily provides better control than inhaled fluticasone or budesonide alone in patients with moderate persistent asthma. European Respiratory Journal 2002;20(Suppl 38):387s.
EDICT {published data only}
    1. Alonso JF, Badiola C, Kielhorn A. Economic evaluation of salmeterol/fluticasone combination versus budesonide plus formoterol in Spain. European Respiratory Journal 2001;18(Suppl 33):49s.
    1. Chuchalin AG, Chovan L, Ringdal N, Whitehead PJ. Advair/seretide (250/50µg bid) shows nocturnal benefit over budesonide 800µg + formoterol 12µg bid in moderate‐severe asthma. American Journal of Respiratory and Critical Care Medicine 2001;163(Suppl 5):A866.
    1. Jenkins C, Wilson J, Rutherford C, Perry AS, Whitehead PJ. Asthma management costs are lower with combination fluticasone/salmeterol (25/50 mcg BD) in a single inhaler than with budesonide (800 mcg BD) plus eformoterol (12 mcg BD) via separate inhalers. Respirology 2002;7(Suppl):A20.
    1. Martin AA, Whitehead PJ, McCarthy TP. Asthma costs with salmeterol/fluticasone combination 50/250mcg bd compared to budesonide 800mcg bd plus formoterol 12mcg bd [Abstract]. American Thoracic Society 99th International Conference. 2003:D034 Poster C43.
    1. Price MJ, Karia N, Whitehead P. Comparison of asthma treatment costs of salmeterol/fluticasone combination product 50/250mcg bid with budesonide 800mcg plus formoterol 12mcg bid. European Respiratory Journal 2000;16(Suppl 31):353s.
Gogtay 2010 {published data only}
    1. Gogtay J A, Balki A, Dalal S, Singh A, Bardapurkar S, Santhanam B, et al. Efficacy and tolerability of a new HFA‐propelled fluticasone/formoterol combination inhaler compared to budesonide/formoterol combination in subjects with moderate to persistent asthma. Chest 2010;138:161A.
Hampel 2007 {published data only}
    1. Hampel FC, Martin P, Mezzanotte WS. Early bronchodilatory effects of budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and albuterol pMDI: 2 randomized controlled trials in adults with persistent asthma previously treated with inhaled corticosteroids. Journal of Asthma 2008;45(4):265‐72. - PubMed
    1. Hampel Jr FC, Martin P, Mazzanotte WS. Early bronchodilatory effects of budesonide formoterol pressurized metered dose inhaler (pMDI) compared with fluticasone propionate salmeterol dry powder inhaler (DPI) and albuterol pMDI in adults with asthma. Journal of Allergy and Clinical Immunology 2008;121(2 Suppl 1):S220.
Jenkins 2000 {published and unpublished data}
    1. Becker I, Kielborn A, Price MJ, Volmer T, Lloyd AC. Cost‐effectiveness of salmeterol/fluticasone combination product and budesonide in asthma patients in Germany. European Respiratory Society; 1999 Oct 9‐13; Madrid, Spain. 1999:854.
    1. GlaxoSmithKline (SAS40006). A randomised, double‐blind, double‐dummy, parallel group comparison of Seretide Diskus/Accuhaler (50/250µg strength) b.i.d. with Budesonide 800µg b.i.d. in adolescents and adults with reversible airways obstruction. http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/IV_SAS40006.pdf (accessed 19 October 2007).
    1. Jenkins C, Woolcock A James M. Superior overall control of moderate to severe asthma with salmeterol/fluticasone propionate (FP) combination (50/250 mcg bd) compared with three‐fold‐higher dose of budesonide (800mcg bd). European Respiratory Journal. 2000; Vol. 16, issue Suppl 31:456s.
    1. Jenkins C, Woolcock AJ, Saarelainen P, Lundbaack B James MH. Salmeterol/fluticasone propionate combination therapy 50/250mcgs twice daily is more effective than budesonide 800 twice daily in treating moderate to severe asthma. Repiratory Medicine 2000;94:715‐23. - PubMed
    1. Lundback B, Jenkins C, Price MJ, Thwaites RM. Cost‐effectiveness of salmeterol/fluticasone propionate combination product 50/250 microg twice daily and budesonide 800 microg twice daily in the treatment of adults and adolescents with asthma. Respiratory Medicine 2000;94(7):724‐32. - PubMed
Kaik 2002 {published data only}
    1. Kaik G, Kottakis I, Anagnostopoulou O, Sichletidis L, Bachlitzanakis N, D'Amato M, et al. Sequential flexible therapy with formoterol (Foradil®) plus budesonide (Miflonide®) versus a fixed combination of salmeterol and fluticasone (Seretide®) in asthma self‐management. European Respiratory Society Annual Congress. 2002:abstract nr: P2407.
Lee 2003 {published data only}
    1. Lee DK, Jackson CM, Currie GP, Cockburn WJ, Lipworth BJ. Comparison of combination inhalers versus inhaled corticosteroids alone in moderate persistent asthma. British Journal of Clinical Pharmacology 2003;56(5):494‐500. - PMC - PubMed
    1. Lee DKC, Currie GP, Cockburn WJ, Lipworth BJ. Budesonide/formoterol and fluticasone/salmeterol combination inhalers delay immediate albuterol recovery following acute bronchoconstriction. Journal of Allergy and Clinical Immunology 2003;111(Suppl 2):202s.
    1. Lee DKC, Currie GP, Cockburn WJ, Lipworth BJ. Comparison of budesonide/formoterol versus fluticasone/salmeterol combination inhalers in moderate persistent asthma. American Thoracic Society 99th International Conference. 2003:D094 Poster 613.
Lötvall 2002 {published data only}
    1. Lötvall J, Woude HJ, Palmqvist M, Arvidsson P, Beckman O, Boorsma M, et al. More rapid onset of action of budesonide/formoterol (Symbicort®) than salmeterol/fluticasone (seretide™). American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A567.
Maspero 2010 {published data only}
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References to other published versions of this review

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