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Abstract: Slide Presentations |

ARGININE 16 GENOTYPE DOES NOT MODULATE CLINICAL RESPONSE TO SALMETEROL IN SUBJECTS WITH ASTHMA FREE TO VIEW

Eugene Bleecker, MD*; Steven Yancey, MS; Hector Ortega, MD; Wayne Anderson, PhD
Author and Funding Information

Wake Forest University School of Medicine, Winston Salem, NC


Chest


Chest. 2007;132(4_MeetingAbstracts):436. doi:10.1378/chest.132.4_MeetingAbstracts.436
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Abstract

PURPOSE: To prospectively evaluate clinical responses to salmeterol, administered with fluticasone propionate (FP) or alone in subjects with asthma and differing ADRB2 polymorphisms at codon 16.

METHODS: Analysis of subjects (≥12 years) randomized by genotype (Arg/Arg, Gly/Gly and Arg/Gly; approximately 90 per group) receiving FP/salmeterol 100/50mcg (FSC) or salmeterol 50mcg BID for 16 weeks, followed by a 2 week run-out period receiving ipratropium bromide as needed.

RESULTS: A total of 534 subjects (mean FEV1 % predicted=82%) were evaluated for efficacy. Baseline demography and asthma history were similar across genotype groups. Over the 16-week treatment, there was sustained improvement in the primary outcome (AM PEF) for both FSC and salmeterol with no statistically significant differences observed across Arg16/Gly subgroups (p≥0.054 for all comparisons). Specifically, mean changes from baseline in AM PEF (L/min) [SE] for FSC over weeks 1-16 were Arg/Arg (n=87; 32.6 L/min [4.71]), Gly/Gly (n=90; 24.9 [5.86]) and Arg/Gly (n=91; 25.9 [4.77]). Mean changes from baseline in AM PEF for salmeterol over weeks 1-16 were Arg/Arg (n=86; 19.4 [3.92]), Gly/Gly (n=91; 12.4 [3.05]) and Arg/Gly (n=89; 24.6 [5.36]). Other measures of asthma control (symptom-free days and supplemental ipratropium or albuterol use) were not statistically different among genotypes for both FSC and salmeterol. Importantly, during the run-out period, subjects (regardless of genotype) had predictable decreases in AM PEF as well as other measures of asthma control. Exacerbations occurred in one FSC-treated subject (Gly/Gly) and in ten salmeterol-treated subjects: ([n=3; Arg/Arg], [n=3; Arg/Gly], [n=4; Gly/Gly]).

CONCLUSION: Findings from this prospective clinical trial show that regardless of Arg16/Gly genotype, the clinical response to salmeterol administered with FP or alone was robust during chronic dosing.

CLINICAL IMPLICATIONS: Although previous retrospective analyses of long-acting beta-agonists have produced conflicting results, this prospective study, the largest to date, concludes that subjects with the Arg/Arg genotype experience similar improvements in asthma control without any deleterious effects compared with Gly/Gly or Arg/Gly subjects, when receiving salmeterol combined with FP or alone. (SFA100062).

DISCLOSURE: Eugene Bleecker, No Product/Research Disclosure Information; Employee Mr. Yancey and Drs. Ortega and Anderson are full-time employees of GalxoSmithKline; Consultant fee, speaker bureau, advisory committee, etc. Dr. Bleecker is a consultant, speaker and serves on advisory committees for GlaxoSmithKine

Monday, October 22, 2007

2:30 PM - 4:00 PM


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