Stanley J Szefler1, Thomas B Casale2, Tmirah Haselkorn3, Bongin Yoo4, Benjamin Ortiz5, Meyer Kattan6, William W Busse7. 1. Pediatric Asthma Research Program, Breathing Institute, Children's Hospital Colorado, and University of Colorado School of Medicine, Aurora, Colo. Electronic address: Stanley.Szefler@childrenscolorado.org. 2. University of South Florida, Tampa, Fla. 3. EpiMetrix, Inc, Los Altos, Calif. 4. Genentech, Inc, South San Francisco, Calif. 5. Novartis Pharmaceuticals Corporation, East Hanover, NJ. 6. Columbia University College of Physicians and Surgeons, New York, NY. 7. University of Wisconsin School of Medicine and Public Health, Madison, Wis.
Abstract
BACKGROUND: Greater severity in childhood asthma negatively impacts functioning and quality of life. Omalizumab is effective in children aged 6 years or older with moderate to severe persistent asthma, but predicting responsiveness in severe disease requires further study. OBJECTIVE: To assess response to omalizumab treatment among children using indicators of asthma severity. METHODS: Post hoc analyses of randomized placebo-controlled studies of omalizumab (Inner-City Anti-IgE Therapy for Asthma [ICATA], IA05, and Preventative Omalizumab or Step-up Therapy for Fall Exacerbations [PROSE]) stratified by body mass index, eosinophil count, fractional exhaled nitric oxide levels, and baseline severity indicators (baseline percent predicted FEV1, previous hospitalizations, asthma exacerbations). Poisson regression analysis examined exacerbation rate reductions for body mass index, biomarkers, and severity indicators. RESULTS:Children aged 6 to 11 years in IA05 (N = 576; 56% white, 17% black, 26% other/missing), ICATA (N = 237; 55% black, 43% Hispanic), and PROSE (N = 342; 59% black, 35% Hispanic) were included. Trends indicative of greater exacerbation rate change ([omalizumab - placebo]/placebo) were observed for low baseline lung function (IA05 percent predicted FEV1: <90%, 36% reduction, 95% CI, -53.3 to -13.5; ≥90%, 22% reduction, 95% CI, -52.1 to 27.5), previous hospitalizations (ICATA: 46% reduction with, 95% CI, -69.7 to -3.9; 24% reduction without, 95% CI, -48.1 to 10.3), frequent baseline exacerbations (IA05: ≥3, 42% reduction, 95% CI, -60.4 to -14.1; <3, 20% reduction, 95% CI, -45.2 to -15.9), and high baseline eosinophil count (IA05: ≥300 cells/μL, 39% reduction, 95% CI, -56.4 to -14.7; <300 cells/μL, 5% reduction, 95% CI, -40.6 to 52.1). CONCLUSIONS:Omalizumab reduces exacerbations in children with moderate to severe persistent allergic asthma, and may provide greater benefit in children with more severe asthma subtypes.
RCT Entities:
BACKGROUND: Greater severity in childhood asthma negatively impacts functioning and quality of life. Omalizumab is effective in children aged 6 years or older with moderate to severe persistent asthma, but predicting responsiveness in severe disease requires further study. OBJECTIVE: To assess response to omalizumab treatment among children using indicators of asthma severity. METHODS: Post hoc analyses of randomized placebo-controlled studies of omalizumab (Inner-City Anti-IgE Therapy for Asthma [ICATA], IA05, and Preventative Omalizumab or Step-up Therapy for Fall Exacerbations [PROSE]) stratified by body mass index, eosinophil count, fractional exhaled nitric oxide levels, and baseline severity indicators (baseline percent predicted FEV1, previous hospitalizations, asthma exacerbations). Poisson regression analysis examined exacerbation rate reductions for body mass index, biomarkers, and severity indicators. RESULTS:Children aged 6 to 11 years in IA05 (N = 576; 56% white, 17% black, 26% other/missing), ICATA (N = 237; 55% black, 43% Hispanic), and PROSE (N = 342; 59% black, 35% Hispanic) were included. Trends indicative of greater exacerbation rate change ([omalizumab - placebo]/placebo) were observed for low baseline lung function (IA05 percent predicted FEV1: <90%, 36% reduction, 95% CI, -53.3 to -13.5; ≥90%, 22% reduction, 95% CI, -52.1 to 27.5), previous hospitalizations (ICATA: 46% reduction with, 95% CI, -69.7 to -3.9; 24% reduction without, 95% CI, -48.1 to 10.3), frequent baseline exacerbations (IA05: ≥3, 42% reduction, 95% CI, -60.4 to -14.1; <3, 20% reduction, 95% CI, -45.2 to -15.9), and high baseline eosinophil count (IA05: ≥300 cells/μL, 39% reduction, 95% CI, -56.4 to -14.7; <300 cells/μL, 5% reduction, 95% CI, -40.6 to 52.1). CONCLUSIONS:Omalizumab reduces exacerbations in children with moderate to severe persistent allergic asthma, and may provide greater benefit in children with more severe asthma subtypes.