TY - JOUR

T1 - Best step-up treatments for children with uncontrolled asthma: A systematic review and network meta-analysis of individual participant data

AU - Cividini, Sofia

AU - Sinha, Ian

AU - Donegan, Sarah

AU - Maden, Michelle

AU - Rose, Katie

AU - Fulton, Olivia

AU - Culeddu, Giovanna

AU - Hughes, Dyfrig

AU - Turner, Steve

AU - Tudor-Smith, Catrin

PY - 2023/10/26

Y1 - 2023/10/26

N2 - Introduction: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids, and international guidelines make different recommendations.Objectives: We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients Methods: We searched MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, the Web of Science platform, NICE Technology Appraisals, the NIHR HTA series, the WHO International Clinical Trials Registry Platform, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β2-agonists (LABAs) or combined with leukotriene receptor antagonists (LTRAs); LTRAs alone; theophylline; placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (Low/Medium/High dose); ICS+LABA; ICS+LTRA; LTRA alone; theophylline; placebo.Results: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials, and aggregate data from 19 trials. Compared to ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44 [95% CrI 0.19–0.90]) and with an increased FEV1 (MD 0.71 [95% CrI 0.35–1.06]). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.Conclusion: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

AB - Introduction: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids, and international guidelines make different recommendations.Objectives: We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients Methods: We searched MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, the Web of Science platform, NICE Technology Appraisals, the NIHR HTA series, the WHO International Clinical Trials Registry Platform, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β2-agonists (LABAs) or combined with leukotriene receptor antagonists (LTRAs); LTRAs alone; theophylline; placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (Low/Medium/High dose); ICS+LABA; ICS+LTRA; LTRA alone; theophylline; placebo.Results: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials, and aggregate data from 19 trials. Compared to ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44 [95% CrI 0.19–0.90]) and with an increased FEV1 (MD 0.71 [95% CrI 0.35–1.06]). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.Conclusion: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

M3 - Article

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

ER -