Abstract
Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting β2-agonists (LABAs), leukotriene receptor antagonists (LTRAs) and long-acting muscarinic antagonists (LAMAs) as add-on treatment to ICS in children and adolescents aged 4–17 years.A literature search identified a total of 29 studies that met the inclusion criteria, including 21 randomised controlled trials (RCTs) of LABAs versus placebo, two RCTs of LAMAs (tiotropium) versus placebo, and four RCTs of LTRA (montelukast), all as add-on to ICS. In these studies, tiotropium and LABAs provided greater improvements in lung function than LTRAs, when compared with placebo as add-on to ICS. Although exacerbation data were difficult to interpret, tiotropium reduced the risk of exacerbations requiring oral corticosteroids when added to ICS, with or without additional controllers. LABAs and LTRAs had a comparable risk of asthma exacerbations with placebo when added to ICS. When adverse events (AEs) or serious AEs were analysed, LABAs, montelukast and tiotropium had a comparable safety profile with placebo.In conclusion, this literature review provides an up-to-date overview of the efficacy and safety of LABAs, LTRAs and LAMAs as add-on to ICS in children and adolescents with asthma. Overall, tiotropium and LABAs have similar efficacy, and provide greater improvements in lung function than montelukast as add-on to ICS. All three controller options have comparable safety profiles.
Highlights
Asthma is one of the most prevalent chronic diseases in childhood [1], yet diagnosing and treating asthma in children remains challenging
No systematic reviews were identified that compared Long-acting muscarinic antagonist (LAMA) with placebo, or Long-acting β2-agonist (LABA), Leukotriene receptor antagonist (LTRA) or LAMAs directly with one another
In this literature review, the addition of once-daily tiotropium and twicedaily LABAs to inhaled corticosteroids (ICS) in children and adolescents provided similar improvements in lung function [11, 13, 14, 24, 28, 29, 31], and greater improvements than with oncedaily LABA vilanterol added onto ICS [28]
Summary
Asthma is one of the most prevalent chronic diseases in childhood [1], yet diagnosing and treating asthma in children remains challenging. There is, a need for more pharmacological options to improve asthma control in children and adolescents whose symptoms are not fully treated with inhaled corticosteroids (ICS). The Global Initiative for Asthma (GINA) recommends that patients with asthma who continue to experience symptoms and/or exacerbations on low-dose ICS have their ICS dose increased and combined with long-acting β2-agonists (LABAs) or other controllers in a step-wise fashion (Fig. 1). GINA recommends as-needed low-dose ICS/formoterol as reliever therapy in all patients > 12 years of age, with short-acting β2-agonists (SABAs) recommended as an alternative reliever medication [4], it should be noted that the recommendation for children is to ensure additional ICS is taken whenever the SABA reliever is given [4]. The goals of asthma management are aligned across all age groups: namely, to achieve good symptom control, maintain normal activity levels, lung function and development, and minimise future risk of exacerbations and side effects associated with medication [4]
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