Monday, June 5, 2017
Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma
Omalizumab is a potent medication approved to treat asthma, which has been shown to improve symptoms as well as decrease flares and use of rescue medications. When it first became available, its long-term safety was not solidly clarified. In the May 2017 issue of JACI, Iribarren and colleagues discuss the results of the post-marketing observational study called EXCELS, which followed patients for five years to determine the long-term effects of omalizumab, with a particular focus on cardiovascular (CV) and cerebrovascular (CBV) events, such as heart attacks and strokes (J Allergy Clin Immunol 2017; 139(5): 1489-1495). Pooled results from previous studies showed a higher incidence of these events, but no clear association with omalizumab use was found.
Iribarren and colleagues looked at nearly 5000 patients on omalizumab and compared them to nearly 3000 that were not on omalizumab. They found that omalizumab is effective for moderate-to-severe asthma. Because more severe asthma, for which omalizumab would be indicated, is both directly and indirectly associated with risks for CV/CBV events, it was expected that there would be a higher rate of CV/CBV adverse events in the omalizumab group. The results showed that patients were 32% more likely to have a CV/CBV event after controlling for other factors.
However, this doesn’t mean that omalizumab causes CV/CBV events. Due to asthma severity and other risk factors, such as the presence of other diseases, the authors conclude that an increased risk cannot be ruled out. Healthcare professionals should be aware of this potential association when counseling patients about starting omalizumab.
It has long been known that many diseases, like asthma, are the result of complex interactions between genes and the environment. But how exactly do these two factors contribute to atopic asthma? In the May 2017 issue of JACI, Yang and colleagues discuss the epigenetic factors involved in the development of childhood asthma (J Allergy Clin Immunol 2017; 139(5): 1478-1488). They looked at nasal brushings from 36 inner-city children with asthma between the ages of 10 and 12 and compared them with nasal brushings from 36 children without asthma. They then looked at patterns of methylation, a way that genes can be chemically modified in order to change their expression. They found that 186 genes were modified in this way. The median percentage in methylation changes between allergic patients and non-allergic patients was 6.8%. This is in line with previous research that shows that there are significant changes in methylation in other airway diseases like chronic obstructive pulmonary disease (COPD) and with cigarette smoking exposure.
This research is important, because it opens up new targets for research, diagnosis, and perhaps even treatment. Future research can focus on what specific environmental changes lead to differences in genetic expression. Additionally, because the normal bacteria in the nose affect methylation patterns, researchers may be able to look at which specific bacterial species impact gene expression. The authors speculate that the methylation markers can be checked to determine disease activity in the future.