Deprescribing montelukast in children with asthma: a systematic review.

BACKGROUND: National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP). OBJECTIVE: To systematically review evidence regarding deprescribing montelukast in CYP with established asthma. DESIGN: Systematic review. DATA SOURCES: Embase, Medline, PubMed and CINAHL were searched up to October 2020. STUDY SELECTION: Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included. RESULTS: The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased. CONCLUSION: Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP. PROSPERO REGISTRATION NUMBER: CRD42020213971.

Adverse drug reactions of leukotriene receptor antagonists in children with asthma: a systematic review.

Background: Asthma is the most common chronic condition of childhood. Leukotriene receptor antagonists (LTRAs) are included in international guidelines for children and young people (CYP), but there have been highly publicised concerns about potential adverse effects. The aim was to identify and understand the reported frequency of adverse drug reactions (ADRs) attributed to LTRAs in CYP with asthma. Methods: Embase, MEDLINE, PubMed and CINAHL were searched up to October 2020. Reference lists of eligible papers were manually screened. Eligible studies identified adverse events attributed to an LTRA in individuals aged between 0 and 18 years diagnosed with asthma. Four different tools were used to assess risk of bias or quality of data to accommodate the papers assessed. Results: The search identified 427 papers after deduplication; 15 were included (7 case reports, 7 case-controlled or cohort studies and 1 randomised control trial (RCT)). 7012 patients were recorded, of which 6853 received an LTRA. 13 papers examined the ADRs attributed to montelukast, one to pranlukast and one to unspecified LTRAs. After language standardisation, 48 ADRs were found, 20 of which were psychiatric disorders. Across all studies, the most commonly reported ADRs were 'anxiety', 'sleep disorders' and 'mood disorders'. The frequency of ADRs could be calculated in seven of the eight studies. Applying standardised frequency terms to the prospective studies and RCT, there were 14 'common' and 'uncommon' ADRs. 'Common' ADRs included 'agitation/hyperactivity/irritability/nervousness', 'aggression' and 'headache'. The case reports showed a similar pattern, describing 46 different ADRs experienced by a total of eight patients. Conclusions: LTRAs have a wide range of suspected ADRs in CYP, predominantly gastrointestinal and neuropsychiatric disorders. Careful monitoring of CYP with asthma is required, both to assess and manage ADRs and to step treatment down when clinically stable. PROSPERO registration number: CRD42020209627.