Tailored second-line therapy in asthmatic children with the Arg16 genotype

The Arg16 ß2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting ß2 agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 µg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score=-0.40 [95% CI (confidence interval), -0.22 to -0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score=-0.47 (95% CI, -0.16 to -0.79); P<0.0001]. Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol, whereas there was no difference in FEV1 (forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg16 genotype, a move towards a personalized medicine approach to management.

CLINICAL PERSPECTIVES

The FDA has recently highlighted concerns about long-term safety of LABA exposure, especially in children.
Our study evaluated second-line therapy in 15% of genetically susceptible asthmatic children possessing the Arg16 genotype.
We show that patients with the Arg16 genotype may fare better by using montelukast than salmeterol as add-on therapy to inhaled corticosteroids. This in turn provides evidence for genotype directed personalized medicine.