Clinical Study Design2,6,7
A large, multicenter, double-blind trial enrolled patients who were symptomatic despite treatment with inhaled corticosteroids (ICS). Eligible patients were randomly allocated to receive subcutaneous omalizumab or matching placebo every 2 or 4 weeks (at least 0.016 mg/kg/IgE [IU/mL] every 4 weeks), and during the first 16 weeks of the study, they were switched to the equivalent doses of inhaled Beclomethasone dipropionate (BDP) (via metered-dose inhaler) to maintain asthma control. The dose of BDP was kept constant during this period (steroid-stable phase), after which patients entered a 12-week steroid-reduction phase whereupon the dose of BDP was reduced by 25% of the baseline dose every 2 weeks for 8 weeks. The lowest dose of BDP required for asthma control was subsequently maintained for the final 4 weeks of the study. Treatment with omalizumab or placebo continued throughout the steroid-reduction phase. With the exception of BDP and inhaled beta-agonist rescue medication (albuterol,100 μg/puff), no other asthma medication was allowed.
Patients completing the core study were eligible to enter a 24-week, double-blind extension phase in which they were maintained on randomized treatment (omalizumab or placebo) and the lowest effective dose of BDP.6,7 The use of concomitant medication was liberalized during the extension phase so that investigators could treat patients with any asthma medication they considered necessary, including switching to other ICS.
An asthma exacerbation was defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of the baseline BDP dose.
The safety and efficacy of XOLAIR were evaluated in 3 randomized, double-blind, placebo-controlled, multicenter trials.
XOLAIR was compared with placebo in 1071 patients aged 12 to 75 years
After a 4-week to 6-week run-in period to establish a stable baseline BDP dose, patients were randomized to receive XOLAIR or placebo in 2 study phases.7
Steroid-stable phase (16 weeks)
Patients received XOLAIR or placebo via subcutaneous injection every 2 or 4 weeks. Baseline BDP dose remained unchanged except for treatment of acute exacerbations.2,6
Steroid-reduction phase (12 weeks)
Patients continued to receive XOLAIR or placebo and a BDP dose reduction was attempted over 8 weeks (forced reduction of 25% every 2 weeks) until discontinuation or worsening of asthma symptoms. If worsening of asthma symptoms occurred, BDP dose was increased. The minimum effective BDP dose that did not result in worsening of asthma symptoms was maintained for the remaining 4 weeks of the study.2,6,7
Extension phase (24 weeks)
During the extension phase, patients were maintained on randomized treatment (XOLAIR or placebo) and the lowest sustainable dose of BDP. The use of other asthma medications was permitted during the extension phase. Investigators were also allowed to switch patients from BDP to other ICS medications if considered necessary.6,7
Dosage and dropout information5
The following chart provides a summary of baseline and end-of-study BDP as well as dropout rates for Studies 1, 2, and the extension phase.