Omalizumab Improves Asthma Control in Inner-City Youth

Results of a randomized, double-blind, placebo-controlled, multicenter trial [N Engl J Med. 2011;364(11):1005-1015] show that the addition of omalizumab to guidelines-based therapy improved asthma control, reduced the need for other medications to control asthma, and nearly eliminated seasonal peaks in exacerbations in inner-city children, adolescents, and young adults with persistent allergic asthma, with added benefit to those who also had allergies. “We believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population,” said the authors, emphasizing that they currently do not advocate for the use of omalizumab outside the current recommendations because of cost and as yet unknown long-term safety in children. Despite aggressive implementation of guidelines-based therapy, achieving asthma control remains difficult in populations, such as inner-city residents, that have a high prevalence of allergic sensitization and a heavy burden of allergen exposure. Omalizumab, a humanized monoclonal anti-IgE antibody, has been shown to reduce exacerbations and symptoms in patients with allergies who have asthma and is currently indicated to treat patients >11 years of age with moderate-to-severe asthma. In the ICATA (Inner-City Anti-IgE Therapy for Asthma) study, 419 patients with persistent asthma were randomized to omalizumab (n=208) and placebo (n=211) to examine the benefit of adding omalizumab to conventional therapy to specifically target the allergic component in patients with persistent asthma regardless of disease severity. All patients in the study were 6 to 20 years of age; had persistent asthma or uncontrolled disease despite long-term therapy or had both persistent asthma and uncontrolled disease if untreated; and had at least 1 positive skin test for a perennial allergen. Of the 419 patients, 73% had moderate-to-severe disease. Patients were randomized after a 4-week run-in period to subcutaneous injections every 2 or 4 weeks, up to 60 weeks, of placebo or omalizumab (75-375 mg). Individual weight and total serum IgE level were used to calculate the dose of omalizumab to ensure a minimum monthly dose of 0.016 mg per kilogram of body weight per international unit of IgE per milliliter. The study found that omalizumab was associated with a significant reduction in the number of days with asthma symptoms compared with placebo (1.48 vs 1.96 days per 2-week interval, or a 24.5% decrease; P<.001), a significant reduction in the proportion of patients who had ≥1 exacerbations (30.3% vs 48.8%; P<.001), and a significant reduction in the percentage of patients who were hospitalized because of asthma (1.5% vs 6.3%; P=.02). In addition, omalizumab maintained the achieved improved asthma control with a reduced need for inhaled glucocorticoids compared with placebo (budesonide-equivalent dose of 663 mcg/day vs 771 mcg/day, respectively; P<.001). For patients who were also sensitized and exposed to cockroach antigen, a subgroup analysis found that patients treated with omalizumab had a reduction of symptoms of 1.1 days per 2-week interval compared with placebo (with a treatment effect of 48.5%). The reduction of symptoms between omalizumab and placebo for patients who were not sensitive to or exposed to cockroach antigen was 0.4 days (with a treatment effect of 20.5%). In addition, a post hoc analysis found that patients in the placebo group had nearly double the average monthly asthma exacerbations during the fall and spring compared with the summer (9.0% and 8.1%, respectively, vs 4.6%; P<.001), whereas patients receiving omalizumab did not experience these seasonal spikes (4.3% and 4.2%, for fall and spring, respectively, vs 3.3% in summer). Overall, omalizumab was associated with significantly more gastrointestinal disorders than placebo (11 events vs 2; P=.02) but significantly fewer hematologic disorders (1 event vs 16; P=.002). Significantly more serious adverse events occurred in the placebo group compared with the omalizumab group (13.7% vs 6.3%; P=.02), primarily due to asthma-related hospitalizations. The authors emphasize that the study may “help identify those patients most likely to have a response to omalizumab and provide insight into novel mechanisms of asthma exacerbations that could lead to improved treatment.”