Medium-dose inhaled corticosteroid plus LABA best for pediatric uncontrolled asthma

Key takeaways:

• Moving from a low-dose inhaled corticosteroid to a medium-dose inhaled corticosteroid plus a long-acting beta agonist benefits children with asthma.
• This treatment lowered exacerbation odds and improved FEV₁.

A medium inhaled corticosteroid dose plus a long-acting beta agonist was found to be the most beneficial step-up treatment option for children with uncontrolled asthma, according to a meta-analysis published in European Respiratory Journal.

“The current recommendation for treating children and adolescents with asthma who are not well-controlled on ICS is to check adherence, inhaler technique and comorbidities first, then consider a ‘step-up’ to their treatment by increasing the dose of ICS or adding another therapy,” Sofia Cividini, MD, MSc, and colleagues wrote.

Cividini was a member of the department of health data science in the Institute of Population Health at The University of Liverpool at the time of the study. Currently, she is an external consultant to the department of epidemiology and public health for the Global Cancer Update Programme at Imperial College London.

“The 2019 GINA guideline recommends the preferred controller for children [aged 6 to 11] years is ‘medium-dose ICS’ or ‘low-dose ICS with LABA,’ which have similar benefits,” Cividini and colleagues added.

“However, the EINSTEIN analysis suggests that the preferred first ‘step-up’ option should be to increase the dose of ICS to a medium dose in combination with LABA, as this has the most beneficial effect on exacerbation prevention and improves asthma control and lung function,” they continued.

In a systematic review of conference abstracts, internal clinical trial registers and eight different databases from July 2014 to May 2023, Cividini and colleagues analyzed results from 144 randomized controlled trials focusing on children/adolescents with uncontrolled asthma on ICS to determine the most beneficial treatment option.

Researchers specifically looked at which of six treatment options — ICS (low/medium/high dose), ICS plus LABA, leukotriene receptor antagonists (LTRA), ICS plus LTRA, theophylline and placebo — lowered the risk for asthma exacerbations and improved asthma control.

From the total cohort, 29 studies (n = 5,494) had individual patient data. Of the remaining studies, 19 had aggregate data.

Researchers compared each pharmacological option with a low dose of ICS to determine which treatment had the most favorable outcomes.

In terms of exacerbations, 40 trials (n = 8,168) reported this outcome. Patients receiving a medium dose of ICS plus LABA had a reduced likelihood for this outcome (OR = 0.44; 95% credibility interval [CrI], 0.19-0.9), and this was found to be the best option during posterior ranking. On the other hand, researchers found fewer benefits with LTRA.

Researchers found results comparable with those above when analyzing the 23 trials (n = 2,518) that reported on FEV₁. Patients receiving a medium dose of ICS plus LABA demonstrated improved lung function (mean difference in FEV₁, 0.71; 95% CrI, 0.35-1.06), and this treatment was “more effective” than several options, including low ICS, medium ICS, high ICS, low ICS plus LABA, high ICS plus LABA and ICS plus LTRA.

Further, this treatment option came out on top on rank probability plots.

When evaluating asthma control results from 16 studies (n = 3,027), the odds for this outcome were similar between various treatments, but researchers noted some uncertainty over this finding.

“There is too much uncertainty to make any firm conclusions about preferred treatment for asthma control and this is supported by the overlapping intervals for the rank probabilities,” Cividini and colleagues wrote.

Notably, no patients from the trials assessed in this meta-analysis died, and a small number of patients had to be admitted to the hospital because of asthma in the five trials that reported this outcome.

“Although more included patients would have led to more precise estimates, we can reasonably conclude that medium-dose ICS with LABA would be recommended for children and adolescents with asthma who are uncontrolled on a low dose of ICS,” Cividini and colleagues wrote.

“Results from the EINSTEIN study will provide clinicians and patients with accessible, high-quality, patient-relevant information to help make evidence-informed treatment choices,” the researchers added. “Earlier identification of the best step-up treatment for a particular child could significantly impact children’s lives with more extensive benefits to society and the NHS.”