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Meta-Analysis
. 2009 Apr 15:(2):CD007313.
doi: 10.1002/14651858.CD007313.pub2.

Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children

Christopher J Cates  1 , Toby J Lasserson
Affiliations
Meta-Analysis

Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children

Christopher J Cates et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Traditionally inhaled treatment for asthma has been considered as preventer and reliever therapy. The combination of formoterol and budesonide in a single inhaler introduces the possibility of using a single inhaler for both prevention and relief of symptoms (single inhaler therapy).

Objectives: The aim of this review is to compare formoterol and corticosteroid in single inhaler for maintenance and relief of symptoms with inhaled corticosteroids for maintenance and a separate reliever inhaler.

Search strategy: We last searched the Cochrane Airways Group trials register in September 2008.

Selection criteria: Randomised controlled trials in adults and children with chronic asthma.

Data collection and analysis: Two review authors independently assessed studies for inclusion and extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes.

Main results: Five studies on 5,378 adults compared single inhaler therapy with current best practice, and did not show a significant reduction in participants with exacerbations causing hospitalisation (Peto OR 0.59; 95% CI 0.24 to 1.45) or treated with oral steroids (OR 0.83; 95% CI 0.66 to 1.03). Three of these studies on 4281 adults did not show a significant reduction in time to first severe exacerbation needing medical intervention (HR 0.96; 95% CI 0.85 to 1.07). These trials demonstrated a reduction in the mean total daily dose of inhaled corticosteroids with single inhaler therapy (mean reduction ranged from 107 to 267 micrograms/day, but the trial results were not combined due to heterogeneity). The full results from four further studies on 4,600 adults comparing single inhaler therapy with current best practice are awaited.Three studies including 4,209 adults compared single inhaler therapy with higher dose budesonide maintenance and terbutaline for symptom relief. No significant reduction was found with single inhaler therapy in the risk of patients suffering an asthma exacerbation leading to hospitalisation (Peto OR 0.56; 95% CI 0.28 to 1.09), but fewer patients on single inhaler therapy needed a course of oral corticosteroids (OR 0.54; 95% CI 0.45 to 0.64). These results translate into an eleven month number needed to treat of 14 (95% CI 12 to 18), to prevent one patient being treated with oral corticosteroids for an exacerbation. The run-in for these studies involved withdrawal of long-acting beta(2)-agonists, and patients were recruited who were symptomatic during run-in.One study included children (N = 224), in which single inhaler therapy was compared to higher dose budesonide. There was a significant reduction in participants who needed an increase in their inhaled steroids with single inhaler therapy, but there were only two hospitalisations for asthma and no separate data on courses of oral corticosteroids. Less inhaled and oral corticosteroids were used in the single inhaler therapy group and the annual height gain was also 1 cm greater in the single inhaler therapy group, [95% CI 0.3 to 1.7 cm].There was no significant difference found in fatal or non-fatal serious adverse events for any of the comparisons.

Authors' conclusions: Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance inhaled corticosteroids. Guidelines and common best practice suggest the addition of regular long-acting beta(2)-agonist to inhaled corticosteroids for uncontrolled asthma, and single inhaler therapy has not been demonstrated to significantly reduce exacerbations in comparison with current best practice, although results of five large trials are awaiting full publication. Single inhaler therapy is not currently licensed for children under 18 years of age in the United Kingdom.

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Figures

Figure 1
Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.
Figure 2
Figure 2. Forest plot of comparison: 1 Adults and Adolescents treated with Single Inhaler Therapy versus Conventional Best Practice, outcome: 1.1 Patients with exacerbations causing hospitalisation.
Figure 3
Figure 3. Forest plot of comparison: 1 Adults and Adolescents treated with Single Inhaler Therapy versus Conventional Best Practice, outcome: 1.2 Patients with exacerbations treated with oral steroids.
Figure 4
Figure 4. Forest plot of comparison: 1 Adults and Adolescents treated with Single Inhaler Therapy versus Conventional Best Practice, outcome: 1.6 Patients with “severe” exacerbation (time to event).
Figure 5
Figure 5. Forest plot of comparison: 2 Adults and Adolescents treated with Single Inhaler Therapy versus higher fixed dose ICS, outcome: 2.1 Patients with exacerbations causing hospitalisation.
Figure 6
Figure 6. Forest plot of comparison: 2 Adults and Adolescents treated with Single Inhaler Therapy versus higher fixed dose ICS, outcome: 2.2 Patients with exacerbations treated with oral steroids.
Figure 7
Figure 7. In the control group 18 people out of 100 had exacerbation treated with oral steroids over 11 months, compared to 11 (95% CI 9 to 12) out of 100 for the active treatment group. NNT(B) = 14, (95% CI 12 to 18).
Figure 8
Figure 8. Forest plot of comparison: 2 Adults and Adolescents treated with Single Inhaler Therapy versus higher fixed dose ICS, outcome: 2.6 Patients with “severe” exacerbation (time to event).
See this image and copyright information in PMC

References

References to studies included in this review

    1. *

    2. AstraZeneca (D5890L00011) [Accessed 3rd September 2008];DESOLO - SiT Peri-Launch: a comparison of symbicort single inhaler therapy and conventional best practice for the treatment of persistent asthma in adults. 2005 clinicaltrials.gov http://www.clinicaltrials.gov/ct/show/NCT00252863. [unpublished data only]
    1. AstraZeneca (D5890L00008) [Accessed 12/04/2006];MONO: Symbicort single inhaler therapy and conventional best standard treatment for the treatment of persistent asthma in adolescents and adults. 2006 clinicaltrials.gov http://www.clinicaltrials.gov/ct/show/NCT00242411. [published data only]
    1. AstraZeneca (BN-00S-0011) [Accessed 22/02/2008];Symbicort single inhaler therapy for asthma in a general practice setting. 2005 www.clinicaltrials.gov. http://www.clinicaltrials.gov/ct/show/NCT00235911. [unpublished data only]
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References to studies excluded from this review

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    6. Price D, Wiren A, Kuna P. Budesonide/formoterol (B/F) as maintenance and relief for asthma improves efficacy and is cost saving versus higher maintenance dose of B/F or salmeterol/fluticasone (S/F) [Abstract] European Respiratory Journal. 2006;28(Suupl 50):214s.
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    2. D’Urzo A, Vogeimeier C, Jaspal M, Merino JM, Boulet S. Symbicort (budesonide/formoterol) for both maintenance and relief reduces the exacerbation burden compared with titration of seretide (salmeterol/fluticasone) in patients with asthma, a real life stud. American Thoracic Society International Conference; San Diego, California. May 20-25; 2005. Poster G24.
    3. Johansson G, Andreasson EB, Larsson PE, Vogelmeier CF. Cost effectiveness of budesonide/formoterol for maintenance and reliever therapy versus salmeterol/fluticasone plus salbutamol in the treatment of asthma. Pharmacoeconomics. 2006;24(7):695–708. - PubMed
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References to ongoing studies

    1. NCT00463866 Ongoing study. 2007 Mar; [unpublished data only]
    1. NCT00628758 Ongoing study. 2006 Mar; [unpublished data only]
    1. Study SPAINA Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 mcg, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults - a 26-Week, Randomised, Open-Label, Parallel-Group, Multicentre Study. Estimated enrolment: 1000. Ongoing study. 2006 Sep; [unpublished data only]
    1. SYMPHONIE Ongoing study. 2005 Sep; [unpublished data only]

Additional references

    1. Adams NP, Bestall JC, Lasserson TJ, Jones PW, Cates CJ. Fluticasone versus placebo for chronic asthma in adults and children. Cochrane Database of Systematic Reviews. 2008;(Issue 4) [DOI: 10.1002/14651858.CD003135.pub4] - PubMed
    1. Barnes PJ. Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control. Bmj. 2007;Vol. 335(issue 7618):513. - PMC - PubMed
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    1. British Thoracic Society British Guidelines on Asthma Management. Thorax. 2008;Vol. 63(issue Suppl 1)
    1. Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious adverse events (Cochrane Review) Cochrane Database of Systematic Reviews. 2008;(Issue 3) [DOI: 10.1002/14651858.CD006363.pub2] - PMC - PubMed

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