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.

Objectives: 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.

Keywords: Asthma exacerbations; Biomarkers; Dosing regimens; Inhaled corticosteroids; Omalizumab; Pharmacodynamics; Response predictors.

FIGURE 1

Dosing status for patients in the ICATA study. A, Shown is where weight and IgE measurements fall in the dosing chart for each of the 889 participants screened in ICATA. Ineligible participants are classified into 3 groups according to where they fall in the dosing chart (IgE <30 IU/mL; weight/IgE combo, and IgE >1300 IU/mL). B, Shown is how participants who are eligible for dosing break down into monthly and biweekly dosing groups. Q4, monthly; Q2, biweekly.

FIGURE 2

Omalizumab time to effect for exacerbations and symptom days. Shown are changes in overall symptoms (top row), exacerbations (middle row), and ICS use (bottom row) between enrollment (week −4) and the end of the double-blind (week 60) in ICATA. Changes in group means (left column) are compared with effect size (right column) to better emphasize the timing of efficacy. The left column shows average effect sizes at the first symptom assessment (4 weeks for symptom days and exacerbations, 12 weeks for ICS) and over the course of the outcome period starting at week 12. During the outcome period, the relative improvement in symptoms was 24.5%, reduction in exacerbations was 37.9%, and reduction in ICS dose was 14.1%. From N Engl J Med. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. Volume 364, pp. 1005–15. Copyright © 2011 Massachusetts Medical Society. Reprinted with permission.

FIGURE 3

Time for omalizumab to lose effect. Shown are changes in symptoms and exacerbations after cessation of injections (omalizumab or placebo) during the ICATA open-label follow-up period. Within 4 months of the final injection, participants taking omalizumab saw increases in symptoms and exacerbations (symptoms: 0.84-day increase, P <.001; exacerbations: 2.8% increase, P =.30) whereas the placebo group remained stable (both P > .30).