Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate.

Published

Journal Article

RATIONALE: Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the beta(2-)adrenergic receptor (position 16) should use long-acting beta-agonists. OBJECTIVES: To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- receptor polymorphisms. METHODS: Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint. MEASUREMENTS AND MAIN RESULTS: Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], -6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, -1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -0.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses. CONCLUSIONS: The results showed no evidence of a pharmacogenetic effect of beta-receptor variation on salmeterol response. Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).

Full Text

Cited Authors

  • Bleecker, ER; Nelson, HS; Kraft, M; Corren, J; Meyers, DA; Yancey, SW; Anderson, WH; Emmett, AH; Ortega, HG

Published Date

  • April 2010

Published In

Volume / Issue

  • 181 / 7

Start / End Page

  • 676 - 687

PubMed ID

  • 19910613

Pubmed Central ID

  • 19910613

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/200809-1511oc

Language

  • eng