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

Abstract

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 <18 years on inhaled corticosteroids.

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 <18 with uncontrolled asthma on any inhaled corticosteroid (ICS) dose alone at 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.Using medium-dose inhaled corticosteroids with long-acting β2-agonists reduces the odds of exacerbation and increases FEV1 in patients 6 to 17 years whose asthma is uncontrolled on a low dose of inhaled corticosteroids alone.

• Authors: Sofia Cividini, Ian Sinha, Sarah Donegan, Michelle Maden, Katie Rose, Olivia Fulton, Giovanna Culeddu, Dyfrig A Hughes, Stephen Turner, Catrin Tudur Smith, PhD on behalf of the EINSTEIN collaborative group
• Journal: The European respiratory journal (Eur Respir J) (Nov 09 2023) ISSN: 1399-3003 [Electronic] England
• PMID: 37945034 (Publication Type: Journal Article)
• Copyright: Copyright ©The authors 2023. For reproduction rights and permissions contact [email protected].