Rates of asthma exacerbations are not affected by beta₂-adrenergic receptor genotype in patients with persistent asthma

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RATIONALE: To evaluate the incidence of asthma exacerbations in subjects with persistent asthma who have differing ADRB2 polymorphisms at codon 16 during treatment with salmeterol plus fluticasone propionate (FP) or montelukast (MON).

METHODS: A retrospective analysis of data from two large, identical randomized trials in which genetic samples were collected in subjects receiving FP/salmeterol 100/50mcg (FSC) BID or MON 10mg QD for 12 weeks. Prior to randomization all patients were receiving short-acting beta₂-agonists only.

RESULTS: Overall, there were 6 exacerbations in the FSC group (n=427) and 20 in the MON group (n=428). Among subjects who underwent genotyping (n=360), results were as follows: FSC: Arg/Arg (n=29), Arg/Gly (n=89) and Gly/Gly (n=65); MON: Arg/Arg (n=30), Arg/Gly (n=84) and Gly/Gly (n=63). Baseline demographics were similar for all genotype subgroups and similar for FSC and MON subjects. Among subjects who underwent genotyping, exacerbations were observed rarely in FSC-treated subjects (n=2) with one occurring in an Arg/Arg subject and the other in an Arg/Gly subject. Further analysis revealed that the exacerbations occurred in subjects with AB and BB haplotypes. Seven genotyped subjects receiving MON experienced an exacerbation: Arg/Arg (n= 1), Arg/Gly (n=5) and Gly/Gly (n=1). Haplotype analysis among Caucasians for MON-recipients revealed one each in subjects with AA and BC haplotypes and two subjects with the AB haplotype.

CONCLUSION: Although exacerbations occurred more frequently in MON recipients, findings from this retrospective analysis show that the rate of exacerbations was similar regardless of genotype in patients receiving FSC or MON. (SAS40020/21)