title: Reassessment of omalizumab-dosing strategies and pharmacodynamics in inner-city children and adolescents.
abstract: BACKGROUND
  Treatment regimens for omalizumab are guided by a dosing table that is based on total serum IgE and body weight. Limited data exist about onset and offset of omalizumab efficacy in children and adolescents or subgroups that most benefit from treatment.
  
  
  OBJECTIVE
  Post hoc analyses were conducted to (1) examine patient characteristics of those eligible and ineligible for omalizumab, (2) describe onset of effect after initiation of omalizumab and offset of treatment effect after stopping therapy, and (3) determine whether the efficacy differs by age, asthma severity, dosing regimen, and prespecified biomarkers.
  
  
  METHODS
  Inner-city children and adolescents with persistent allergic asthma were enrolled in the Inner-City Anti-IgE Therapy for Asthma trial that compared omalizumab with placebo added to guidelines-based therapy for 60 weeks.
  
  
  RESULTS
  Two hundred ninety-three of 889 participants (33%) clinically suitable for omalizumab were ineligible for dosing according to a modified dosing table specifying IgE level and body weight criteria. Baseline symptoms were comparable among those eligible and ineligible to receive omalizumab, but other characteristics (rate of health care utilization and skin test results) differed. The time of onset of omalizumab effect was <30 days and time of offset was between 30 and 120 days. No difference in efficacy was noted by age or asthma severity, but high exhaled nitric oxide, blood eosinophils, and body mass index predicted efficacy.
  
  
  CONCLUSIONS
  A significant portion of children and adolescents particularly suited for omalizumab because of asthma severity status may be ineligible due to IgE >1300 IU/mL. Omalizumab reduced asthma symptoms and exacerbations rapidly; features associated with efficacy can be identified to guide patient selection.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: sorkness@wisc.edu.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: Rho Federal Systems Division, Inc, Chapel Hill, NC.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Wildfire
authors.affiliation: Rho Federal Systems Division, Inc, Chapel Hill, NC.
authors.forename: Agustin
authors.initials: A
authors.lastname: Calatroni
authors.affiliation: Rho Federal Systems Division, Inc, Chapel Hill, NC.
authors.forename: Herman E
authors.initials: HE
authors.lastname: Mitchell
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Boston University School of Medicine, Boston, Mass.
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.affiliation: Children's Memorial Hospital, Chicago, Ill.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pongracic
authors.affiliation: Case Western Reserve University, Cleveland, Ohio.
authors.forename: Kristie
authors.initials: K
authors.lastname: Ross
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Tex.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Gill
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.affiliation: University of Arizona College of Medicine, Tucson, Ariz.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Morgan
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Teach
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gergen
authors.affiliation: National Jewish Health and University of Colorado School of Medicine, Denver, Colo.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Liu
authors.affiliation: National Jewish Health and University of Colorado School of Medicine, Denver, Colo.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D000069444:Omalizumab
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D000069444:Omalizumab; D007073:Immunoglobulin E
keywords: Asthma exacerbations; Biomarkers; Dosing regimens; Inhaled corticosteroids; Omalizumab; Pharmacodynamics; Response predictors