IMPORTANCE: Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.
OBJECTIVE: To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.
DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest.
DATA EXTRACTION AND SYNTHESIS: Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength of evidence grading were completed by 2 independent reviewers.
MAIN OUTCOMES AND MEASURES: Asthma exacerbations.
RESULTS: The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, -6.4% [95% CI, -10.2% to -2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, -2.8% [95% CI, -5.2% to -0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, -12.0% [95% CI, -22.5% to -1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, -23.2% [95% CI, -33.6% to -12.1%]).
CONCLUSIONS AND RELEVANCE: In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.
OBJECTIVE: To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma.
DESIGN: Systematic review and network meta-analysis using Bayesian statistics.
DATA SOURCES: Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. ELIGIBILITY CRITERIA TRIALS OF Adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome.
RESULTS: 64 trials with 59,622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy.
CONCLUSIONS: Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.
PURPOSE OF REVIEW: Guidelines for clinical practice are expected to gather evidence-based recommendations to support optimal medical behaviours. The aim of the current review is to explore how currently available research regarding the strategy of using budesonide/formoterol (BUD/FORM) as maintenance and reliever therapy (Symbicort SMART) covers the items considered by the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) system, through a comparative analysis of methodological approaches, clinical outcomes, patient-reported outcomes and costs, in order to highlight uncovered areas. RECENT FINDINGS: Thirteen trials providing data on 21 095 analysed patients were available. No serious limits in methodological study features were found. Evaluation of the clinical outcome was consistent with the efficacy of BUD/FORM maintenance and reliever therapy. As the time to first exacerbation was the primary outcome in most of the studies, conclusive indications cannot be drawn regarding other clinical outcomes or patient-reported outcomes, which were investigated as secondary outcomes. A comprehensive systematic review exploring all critical and important outcomes is desirable, but further research concerning the safety issues of Long Acting [beta]2 Agonists (LABA) and patients' reported outcomes about the SMART in respect to alternative strategies is likely to affect a clear recommendation in the near future. SUMMARY: The efficacy of BUD/FORM maintenance and reliever therapy in extending the time to first exacerbation appears consistent between studies. Further studies exploring all patients' important outcomes are needed. Clinical and economic assessments are worthy of being investigated to verify the directness of the evidence in respect to real life patients and different geographical realities.
BACKGROUND: Asthma's cost-effectiveness is a major consideration in the evaluation of its treatment options. Our objective was to perform a systematic review of the cost-effectiveness of asthma medications.
METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, OHE-HEED, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessments Database, NHS Economic Evaluation Database, and Web of Science and reviewed references from key articles between 1990 and Jan 2008.
RESULTS: A total of 49 RCTs met the inclusion criteria. Maintenance therapy with inhaled corticosteroids was found to be very cost-effective and in uncontrolled asthmatics patients currently being treated with ICS, the combination of an ICS/LABA represents a safe, cost-effective treatment. The simplified strategy using budesonide and formoterol for maintenance and reliever therapy was also found to be as cost-effective as salmeterol/fluticasone plus salbutamol. Omalizumab was found to be cost-effective. An important caveat with regard to the published literature is the relatively high proportion of economic evaluations which are funded by the manufacturers of specific drug treatments.
CONCLUSION: Future studies should be completed independent of industry support and ensure that the comparator arms within studies should include dosages of drugs that are equivalent.
OBJECTIVE: This systematic review examines the published evidence on the pharmacoecomonics of Symbicort®. Symbicort is a combination inhaler used in asthma and chronic obstructive pulmonary disease (COPD) that contains budesonide and formoterol. In asthma, Symbicort can be used as fixed or adjustable dose maintenance therapy as well as for both maintenance and reliever therapy (SMART).
METHOD: A literature search of PubMed was carried out to find all publications on the pharmacoeconomics of Symbicort. Additional studies were searched for in the reference lists of the papers retrieved and by searching tables of contents of relevant journals. A total of 13 studies on Symbicort in asthma and 2 studies on Symbicort in COPD were found.
RESULTS: Total costs were lower with Symbicort than with separate inhalers containing budesonide and formoterol. Adjustable dosing maintained control of asthma using less medication and was associated with lower treatment costs than fixed dosing with Symbicort or the combination of fluticasone/salmeterol. SMART improves asthma control, reduces exacerbations and reduces direct and indirect costs compared to fixed maintenance therapy with either Symbicort or fluticasone/salmeterol. In COPD, Symbicort offers clinical advantages over therapy with the monocomponents and these are achieved at little or no extra cost.
Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.
OBJECTIVE:
To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.
DATA SOURCES AND STUDY SELECTION:
The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest.
DATA EXTRACTION AND SYNTHESIS:
Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength of evidence grading were completed by 2 independent reviewers.
MAIN OUTCOMES AND MEASURES:
Asthma exacerbations.
RESULTS:
The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, -6.4% [95% CI, -10.2% to -2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, -2.8% [95% CI, -5.2% to -0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, -12.0% [95% CI, -22.5% to -1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, -23.2% [95% CI, -33.6% to -12.1%]).
CONCLUSIONS AND RELEVANCE:
In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.
