Effect of β2 -adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial

• Published in: The Lancet (British edition) 2009-11, Vol.374 (9703), p.1754-1764
• Main Authors: Wechsler, Michael E, Dr, Kunselman, Susan J, MA, Chinchilli, Vernon M, Prof, Bleecker, Eugene, Prof, Boushey, Homer A, Prof, Calhoun, William J, Prof, Ameredes, Bill T, PhD, Castro, Mario, MD, Craig, Timothy J, Prof, Denlinger, Loren, MD, Fahy, John V, Prof, Jarjour, Nizar, Prof, Kazani, Shamsah, MD, Kim, Sophia, MD, Kraft, Monica, Prof, Lazarus, Stephen C, Prof, Lemanske, Robert F, Prof, Markezich, Amy, MD, Martin, Richard J, Prof, Permaul, Perdita, MD, Peters, Stephen P, Prof, Ramsdell, Joe, Prof, Sorkness, Christine A, Prof, Sutherland, E Rand, MD, Szefler, Stanley J, Prof, Walter, Michael J, MD, Wasserman, Stephen I, Prof, Israel, Elliot, MD
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; General aspects; Internal Medicine; Medical sciences; Pneumology
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)61492-6

Summary Background Some studies suggest that patients with asthma who are homozygous for arginine at the 16th aminoacid position of the β2 -adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting β2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting β2 agonist in combination with inhaled corticosteroid. Methods In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting β2 agonist (salmeterol 50 μg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 μg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00200967. Findings After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21·4 L/min (95% CI 11·8–31·1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p