BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS:Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.
RCT Entities:
BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS: Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.
Authors: Kelan G Tantisira; Amy Damask; Stanley J Szefler; Brooke Schuemann; Amy Markezich; Jessica Su; Barbara Klanderman; Jody Sylvia; Rongling Wu; Fernando Martinez; Homer A Boushey; Vernon M Chinchilli; Dave Mauger; Scott T Weiss; Elliot Israel Journal: Am J Respir Crit Care Med Date: 2012-04-26 Impact factor: 21.405
Authors: Niloufar Farzan; Susanne J Vijverberg; Anand K Andiappan; Lambang Arianto; Vojko Berce; Natalia Blanca-López; Hans Bisgaard; Klaus Bønnelykke; Esteban G Burchard; Paloma Campo; Glorisa Canino; Bruce Carleton; Juan C Celedón; Fook Tim Chew; Wen Chin Chiang; Michelle M Cloutier; Denis Daley; Herman T Den Dekker; F Nicole Dijk; Liesbeth Duijts; Carlos Flores; Erick Forno; Daniel B Hawcutt; Natalia Hernandez-Pacheco; Johan C de Jongste; Michael Kabesch; Gerard H Koppelman; Vangelis G Manolopoulos; Erik Melén; Somnath Mukhopadhyay; Sara Nilsson; Colin N Palmer; Maria Pino-Yanes; Munir Pirmohamed; Uros Potočnik; Jan A Raaijmakers; Katja Repnik; Maximilian Schieck; Yang Yie Sio; Rosalind L Smyth; Csaba Szalai; Kelan G Tantisira; Steve Turner; Marc P van der Schee; Katia M Verhamme; Anke H Maitland-van der Zee Journal: Pharmacogenomics Date: 2017-06-22 Impact factor: 2.533
Authors: Laura E Crotty Alexander; Kathryn Akong-Moore; Stephanie Feldstein; Per Johansson; Anh Nguyen; Elisa K McEachern; Shari Nicatia; Andrew S Cowburn; Joshua Olson; Jae Youn Cho; Hart Isaacs; Randall S Johnson; David H Broide; Victor Nizet Journal: J Mol Med (Berl) Date: 2012-12-19 Impact factor: 4.599