Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.
The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.
"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.
The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.
At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.
The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).
Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.
These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).
"No differences of concern regarding safety were noted between the two groups," they added.
The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.
"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.
"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.
In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.
"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.
These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.
This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.