Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations - 04/12/15
, Michelle A. Gill, MD, PhD b, Alkis Togias, MD c, Christine A. Sorkness, PharmD d, Samuel J. Arbes, DDS, MPH, PhD e, Agustin Calatroni, MA, MS e, Jeremy J. Wildfire, MS e, Peter J. Gergen, MD, MPH c, Robyn T. Cohen, MD, MPH f, Jacqueline A. Pongracic, MD g, Carolyn M. Kercsmar, MD h, Gurjit K. Khurana Hershey, MD, PhD h, Rebecca S. Gruchalla, MD, PhD b, Andrew H. Liu, MD i, l, Edward M. Zoratti, MD j, Meyer Kattan, MD k, Kristine A. Grindle, BS d, James E. Gern, MD d, William W. Busse, MD d, Stanley J. Szefler, MD lAbstract |
Background |
Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure.
Objective |
We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school.
Methods |
A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined.
Results |
Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms.
Conclusions |
Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, fall season, omalizumab, inhaled corticosteroid, asthma exacerbations, rhinovirus, IFN-α
Abbreviations used : AE, EPR3, Feno, ICAC, ICATA, ICS, mITT, NIAID, OR, PROSE
Plan
| This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contracts HHSN272200900052C and HHSN272201000052I. Additional support was provided by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCRR/NIH UL1TR000451, 1UL1RR025780, UL1TR000075 and NCATS/NIH UL1 TR000154, UL1 TR000077-04, NCATS/NIH UL1TR000040, UL1TR000150, and UL1TR001105, NIH NIAID 5R01AI098077, and UM1AI109565. The following were donated: omalizumab and matching placebo by Novartis and fluticasone and matching placebo by GlaxoSmithKline under a clinical trial agreement with the University of Wisconsin–Madison; EpiPens by Mylan; and Ayr nasal rinse by B.F. Ascher & Company. |
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| Disclosure of potential conflict of interest: S. J. Teach has received grants from Novartis, PCORI, the Fight for Children Foundation, the Stewart Foundation, EJF Philanthropies, the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), and the NIH/National Heart, Lung, and Blood Institute (NHLBI). M. Gill has received grants from the NIH/NIAID Inner City Asthma Consortium II and the NIH/NIAID R01. C. A. Sorkness has received grants from the NIH/NIAID, the NIH/NHLBI, and Novartis. S. J. Arbes has a contract with the NIH/NIAID. A. Calatroni, J. J. Wildfire, and K. A. Grindle have received grants from the NIH/NIAID. J. A. Pongracic received the study drug for this study from Genentech, has a subcontract for the NIAID-sponsored Inner City Asthma Consortium from the University of Wisconsin and has received the study drug for a food allergy clinical trial from Genentech. C. M. Kercsmar has received a grant from the NIH and has received personal fees from GlaxoSmithKline. G. K. Khurana Hershey and E. M. Zoratti have received grants from the NIH. R. S. Gruchalla has served as a special government employee for the Center for Biologics Evaluation and Research and has consulted for the Massachusetts Medical Society. A. H. Liu has served as a member of a data monitoring committee for GlaxoSmithKline and has received payment for lectures from Merck. M. Kattan has received a grant from the NIH/NIAID and is on the advisory board for Novartis Pharma. J. E. Gern has received grants from the NIH, GlaxoSmithKline, and Merck; has consultant arrangements with GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Genentech, Amgen, and Novartis; and has stock/stock options in 3V BioSciences. W. W. Busse has received grants from the NIH/NIAID; has received partial study funding, drug, and placebo from Novartis; is on Data Safety Monitoring Boards for Boston Scientific and Circassia; is on the Study Oversight Committee for ICON; and has consultant arrangements with Novartis, GlaxoSmithKline, Genentech, Roche, Pfizer, Merck, Boehringer Ingelheim, Sanofi, AstraZeneca, Gilead, Teva, Tekeda, and Aerocrine. S. J. Szefler has received grants from the NIAID-sponsored Inner City Asthma Consortium and GlaxoSmithKline; has consultant arrangements with Merck, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Aerocrine, Novartis, and AstraZeneca; and has received payment for lectures from Merck. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 6
P. 1476-1485 - décembre 2015 Retour au numéro
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