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Prescribing Advice for GPs

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Genes alter LABA response

Clinical Science has published the results of a small randomised study that aimed to assess the efficacy of a tailored second-line asthma therapy in 62 children with poorly controlled asthma. This study has been reported in the wider media (BBC).

The 62 participants all had the homozygous Arginine-16 beta-receptor genotype which is already known to decrease response to LABA medication and thus increase susceptibility to exacerbations and poor control. They were randomly assigned to treatment with salmeterol at a dose of 50micrograms twice daily or montelukast at 5mg or 10mg daily (depending on age). Participants were followed up for 1 year.

The primary outcome was absence from school with secondary measures including salbutamol use, quality of life and FEV1. Absence from school was significantly lower in the montelukast group (−0.40, 95% CI −0.22 to −0.58, P=0.005). There were also a significant reduction in salbutamol use and improvements in quality of life measures, however FEV1 was unchanged.

The authors conclude that, "montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arginine-16 genotype".

The authors note some limitations in the study. The individuals randomised to treatment with montelukast had received more courses of oral steroids in the year before the study so perhaps they had greater room for improvement in their symptoms, however it is also noted that in other scores of disease severity the two arms of the study were similar.

It is also worth noting that this study was exclusively in children, it is unknown if the effects seen replicate in adults. Finally, this study used a test that is currently not available to assess genotype.

The current Asthma Guideline from the British Thoracic Society and SIGN recommends trialling the addition of a LABA at step 3 with a recommendation to stop and try alternatives if there is a poor response.

Action: Clinicians should be aware of this study and the wider media reporting. This study highlights an interesting avenue of research into tailored treatments but this study alone should not change current practice.

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