To evaluate clinical responses to the inhaled long-acting beta2-agonist (LABA), salmeterol, administered with fluticasone propionate (FP) in asthma patients with differing ADRB2 polymorphisms at codon 16.
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 for 12 weeks, followed by a 2-4 day run-out period in which subjects received as needed albuterol only.
Among subjects randomized to FSC who underwent genotyping (n=183), results were as follows: Arg/Arg (n=29), Arg/Gly (n=89) and Gly/Gly (n=65). Baseline demographics were similar for all genotype subgroups. Over the 12 week studies, there was sustained significant improvement (p<0.001) compared with baseline for all measures of asthma control (e.g., lung function, symptoms, albuterol use) with no differences observed across Arg16/Gly subgroups. Specifically, changes from baseline over weeks 1-12 in AM PEF were similar for Gly/Gly and Arg/Arg genotype (estimated difference=4.7 ± 16.3 L/min; 95% CI= -27.4, 36.7; p=0.774) and for the Arg/Gly and Arg/Arg genotype (estimated difference=3.51 ± 15.6 L/min; 95% CI= -27.2, 34.2; p=0.822). Importantly, during the run-out period, patients, regardless of genotype, had predictable and similar decreases in AM PEF as well as other measures of asthma control. Of note, 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.
Findings from this retrospective analysis in 183 patients show that regardless of Arg16/Gly genotype, the clinical response to salmeterol in the presence of an ICS was robust during chronic dosing.
Current guidelines advocate the use of a LABA and ICS for the treatment of persistent asthma. Although prospective studies are needed to fully understand the effect of ADRB2 polymorphisms on response to LABA therapy, this analysis would suggest that these recommendations are valid for patients with differing Arg16/Gly genotypes. (SAS40020/21).
P.M. Dorinsky, None.