BACKGROUND: The efficacy and safety of inhaled long-acting β(2)-adrenergic agonists in asthmatic patients with the B16-Arg/Arg genotype has been questioned, and the use of antimuscarinics has been proposed as an alternative in patients whose symptoms are not controlled by inhaled corticosteroids (ICSs). OBJECTIVE: We compared the efficacy and safety of the long-acting anticholinergic tiotropium with salmeterol and placebo added to an ICS in B16-Arg/Arg patients with asthma that was not controlled by ICSs alone. METHODS: In a double-blind, double-dummy, placebo-controlled trial, after a 4-week run-in period with 50 μg of twice-daily salmeterol administered through a metered-dose inhaler, 388 asthmatic patients were randomized 1:1:1 to 16 weeks of treatment with 5 μg of Respimat tiotropium administered daily in the evening, 50 μg of salmeterol administered twice daily through a metered-dose inhaler, or placebo. Patients aged 18 to 67 years demonstrated reversibility to bronchodilators, and their symptoms were uncontrolled by regular ICSs (400-1000 μg of budesonide/equivalent). ICS regimens were maintained throughout the trial. The mean weekly morning peak expiratory flow (PEF) before randomization was 358 ± 115.7 L/min (range, 80.3-733.0 L/min). RESULTS: Changes in weekly PEF from the last week of the run-in period to the last week of treatment (primary end point: change in PEF) were -3.9 ± 4.87 L/min (n = 128) for tiotropium and -3.2 ± 4.64 L/min (n = 134) for salmeterol, and these were superior to placebo (-24.6 ± 4.84 L/min, n = 125, P < .05). Tiotropium was noninferior to salmeterol (estimated difference, -0.78 L/min [95% CI, -13.096 to 11.53]; P = .002; α = .025, 1-sided; noninferiority, 20 L/min). Tiotropium and salmeterol were numerically superior to placebo in some patient-reported secondary outcomes. Adverse events were comparable across treatments. CONCLUSION:Tiotropium was more effective than placebo and as effective as salmeterol in maintaining improved lung function in B16-Arg/Arg patients with moderate persistent asthma. Safety profiles were comparable.
RCT Entities:
BACKGROUND: The efficacy and safety of inhaled long-acting β(2)-adrenergic agonists in asthmatic patients with the B16-Arg/Arg genotype has been questioned, and the use of antimuscarinics has been proposed as an alternative in patients whose symptoms are not controlled by inhaled corticosteroids (ICSs). OBJECTIVE: We compared the efficacy and safety of the long-acting anticholinergic tiotropium with salmeterol and placebo added to an ICS in B16-Arg/Argpatients with asthma that was not controlled by ICSs alone. METHODS: In a double-blind, double-dummy, placebo-controlled trial, after a 4-week run-in period with 50 μg of twice-daily salmeterol administered through a metered-dose inhaler, 388 asthmatic patients were randomized 1:1:1 to 16 weeks of treatment with 5 μg of Respimat tiotropium administered daily in the evening, 50 μg of salmeterol administered twice daily through a metered-dose inhaler, or placebo. Patients aged 18 to 67 years demonstrated reversibility to bronchodilators, and their symptoms were uncontrolled by regular ICSs (400-1000 μg of budesonide/equivalent). ICS regimens were maintained throughout the trial. The mean weekly morning peak expiratory flow (PEF) before randomization was 358 ± 115.7 L/min (range, 80.3-733.0 L/min). RESULTS: Changes in weekly PEF from the last week of the run-in period to the last week of treatment (primary end point: change in PEF) were -3.9 ± 4.87 L/min (n = 128) for tiotropium and -3.2 ± 4.64 L/min (n = 134) for salmeterol, and these were superior to placebo (-24.6 ± 4.84 L/min, n = 125, P < .05). Tiotropium was noninferior to salmeterol (estimated difference, -0.78 L/min [95% CI, -13.096 to 11.53]; P = .002; α = .025, 1-sided; noninferiority, 20 L/min). Tiotropium and salmeterol were numerically superior to placebo in some patient-reported secondary outcomes. Adverse events were comparable across treatments. CONCLUSION:Tiotropium was more effective than placebo and as effective as salmeterol in maintaining improved lung function in B16-Arg/Argpatients with moderate persistent asthma. Safety profiles were comparable.
Authors: T E Albertson; M Schivo; N Gidwani; N J Kenyon; M E Sutter; A L Chan; S Louie Journal: Clin Rev Allergy Immunol Date: 2015-02 Impact factor: 8.667
Authors: Mohamed S Al-Moamary; Sami A Alhaider; Abdullah A Alangari; Mohammed O Al Ghobain; Mohammed O Zeitouni; Majdy M Idrees; Abdullah F Alanazi; Adel S Al-Harbi; Abdullah A Yousef; Hassan S Alorainy; Mohamed S Al-Hajjaj Journal: Ann Thorac Med Date: 2019 Jan-Mar Impact factor: 2.219
Authors: Stephen C Lazarus; Jerry A Krishnan; Tonya S King; Jason E Lang; Kathryn V Blake; Ronina Covar; Njira Lugogo; Sally Wenzel; Vernon M Chinchilli; David T Mauger; Anne-Marie Dyer; Homer A Boushey; John V Fahy; Prescott G Woodruff; Leonard B Bacharier; Michael D Cabana; Juan C Cardet; Mario Castro; James Chmiel; Loren Denlinger; Emily DiMango; Anne M Fitzpatrick; Deborah Gentile; Annette Hastie; Fernando Holguin; Elliot Israel; Daniel Jackson; Monica Kraft; Craig LaForce; Robert F Lemanske; Fernando D Martinez; Wendy Moore; Wayne J Morgan; James N Moy; Ross Myers; Stephen P Peters; Wanda Phipatanakul; Jacqueline A Pongracic; Loretta Que; Kristie Ross; Lewis Smith; Stanley J Szefler; Michael E Wechsler; Christine A Sorkness Journal: N Engl J Med Date: 2019-05-19 Impact factor: 91.245
Authors: Diana M Sobieraj; William L Baker; Elaine Nguyen; Erin R Weeda; Craig I Coleman; C Michael White; Stephen C Lazarus; Kathryn V Blake; Jason E Lang Journal: JAMA Date: 2018-04-10 Impact factor: 56.272