The findings are part of a clinical trial run by the Inner-City Asthma Consortium (ICAC), an asthma research program led by investigators at the University of Wisconsin School of Medicine and Public Health and funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH).
The study findings, reported online on Oct. 27 in the Journal of Allergy and Clinical Immunology, also show that short-term treatment with the medication, omalizumab, was highly effective at preventing 90% of additional attacks in school-aged children who had had an exacerbation earlier that year. Asthma exacerbations—worsening of asthma symptoms—disrupt quality of life and contribute significantly to morbidity associated with asthma.
“Our research suggests a new therapeutic strategy that may help prevent seasonal asthma attacks in high-risk children,” said Dr. William Busse, professor of medicine at UW and principal investigator of the ICAC project. “If these attacks are prevented, thousands of children who would otherwise fall behind from missing critical classroom time will have a healthy and successful start to the school year. What’s more, this preventive treatment strategy can also reduce overall disease morbidity and avoid the need for ER visits and hospital admissions.”
Asthma exacerbations typically spike in the fall, with several factors contributing to this seasonal trend, including infections with cold-causing viruses and exposure to respiratory allergens. A previous ICAC study found that adding year-round treatment with omalizumab (brand name Xolair) to guidelines-based asthma care decreased the number of seasonal episodes of worsening asthma, with the most striking effects observed during the fall. Based on these results, ICAC investigators sought to determine whether short-term treatment with omalizumab and targeted to the time of year when exacerbations are most likely to occur (right before children return to school) would have a similar effect. The drug currently is approved in the United States for patients ages 12 and older with moderate-to-severe persistent allergic asthma.
In the current study, researchers enrolled asthmatic children 6 to 17 years of age in eight U.S. cities before the fall seasons and their return to school in 2012 and 2013. All participants first received four to nine months of guidelines-based care to achieve asthma control. Guidelines-based care focuses on measures to assess and monitor asthma, patient education, medications and control of environmental factors and other conditions that can worsen asthma.
Asthmatic participants were then randomly assigned to receive omalizumab or placebo. Participants receiving lower doses of inhaled corticosteroids were randomly assigned to receive omalizumab, placebo or an inhaled corticosteroid boost (in which their normal dose was doubled). These treatments began four to six weeks before the start of school and ended 90 days after school started. All children continued to receive guidelines-based asthma care throughout the study. Complications and side effects were rare and did not differ between the study groups.
Based on analysis of data from 478 study participants, the researchers found that, overall, children treated with omalizumab were about half as likely to experience an asthma exacerbation during the first 90 days of the school year as those who did not receive the drug.
Further analysis revealed that children who had had an exacerbation in the four-to-nine-month period before omalizumab treatment benefited most from the drug. Within this group, omalizumab reduced the risk of an exacerbation by more than 80 percent—36.3 percent of children who received placebo had at least one fall exacerbation, compared to only 6.4 percent of children who received omalizumab. Children who did not have an exacerbation in the months before school were not helped by addition of the drug to their asthma regimens. In children with easier-to-control asthma, the inhaled corticosteroid boost did not help prevent exacerbations, regardless of their history of exacerbations in the previous months.
“This study’s most exciting result demonstrates how clinicians can individualize care for young patients with certain high-risk clinical profiles. This is an important step forward in advancing asthma care, with large benefits for some of the most at-risk, underserved children,” said Dr. Stephen J. Teach, of Children’s National Health System, the lead author of the study.
The cost of omalizumab is a limitation for many who may need it, but this study helps identify populations most likely to respond to pre-seasonal treatment. For those patients, the reduced cost of treatment for only the fall season compared with a full year of treatment might be justifiable.
In addition, there is evidence that some patients with asthma have deficient generation of anti-viral mediators, like interferons, which may contribute to the likelihood that a viral respiratory infection will provoke an exacerbation. To evaluate this aspect of asthma and its relationship to exacerbations, a sub-group of participants were studied. Blood samples were obtained prior to the study and at its completion. The obtained blood cells were incubated with the exacerbation provoking virus, rhinovirus, and the generation of the anti-viral mediator, interferon, was measured. In those who received omalizumab, there was a significant increase in the generation of interferon. Moreover, the degree to which interferon generation was restored was associated with a reduction in asthma exacerbation. These preliminary data suggest that an additional benefit of omalizumab was a restoration of anti-viral activity which may have contributed to the reduction in asthma exacerbations.
Future work may provide additional insight into the causes of fall asthma exacerbations and how best to prevent them.
The study was conducted by ICAC researchers at inner-city hospitals and academic institutions in Baltimore, Boston, Chicago, Cincinnati, Dallas, Denver, Detroit, New York, St. Louis, and Washington, D.C. The project was supported by the NIAID under award numbers N01AI90052 and UM1AI114271 and from an unrestricted grant from Novartis, the makers of omalizumab. Novartis donated omalizumab and matching placebo, GlaxoSmithKline donated inhaled corticosteroid fluticasone and matching placebo. Both companies also had the opportunity to comment on the study design but had no role in the trial’s performance, data analysis, or manuscript preparation.
University of Wisconsin School of Medicine and Public Health