Precision medicine in childhood asthma
Published online: May 3, 2020
In the past decade, there have been significant advances in targeted therapies for pediatric asthma. One such medication is omalizumab, a monoclonal antibody that blocks Immunoglobulin E (IgE), the antibody associated with allergies and allergic asthma. Omalizumab is an effective treatment for persistent allergic asthma in both adult and pediatric populations. Furthermore, treatment with omalizumab has been shown to reduce the spike of pediatric asthma exacerbations during the fall season when children return to school. While omalizumab is an effective therapy in these children, there are other considerations. It is expensive; and it is given as regular injections at a health-care provider’s office requiring a strong commitment from the child and family. With these concerns and the goal to do what is best for the child, it is important to consider which specific children will have the greatest improvements and should be prioritized for omalizumab therapy. In a recent article published in The Journal of Allergy and Clinical immunology: In Practice, Sheehan et al. identify pre-treatment biomarkers that predict children who will most benefit from fall season treatment with omalizumab.
The analysis included inner-city children and adolescents aged 6-20 years with persistent asthma and recent exacerbations. These participants had either been treated with omalizumab or placebo in 2 completed randomized clinical trials from the Inner-City Asthma Consortium. Statistical models were developed to investigate the relationship between greater degrees of the three pre-treatment markers: (1) total number of positive environmental allergies, (2) total serum IgE level, and (3) total serum eosinophil level within the individual, and the success of omalizumab at preventing the primary outcome of fall season asthma exacerbations.
In total, 761 participants who had completed the omalizumab trials were included in the analysis with 62% male, 59% African American, and a median age of 10 years. Among children treated with placebo, those with higher numbers of environmental allergies had significantly higher risk of a fall season asthma exacerbation. In contrast, in children treated with omalizumab, the relationship was flat with an equal risk an asthma exacerbation even with increasing numbers of environmental allergies in those individuals. Similar patterns were seen when the other 2 predictors, serum IgE level and serum eosinophil level were evaluated. When all 3 predictors were compared to each other, the number of environmental allergies was the best predictor of response to omalizumab as treated participants allergic to ≥4 different groups of allergens had a 51% reduction in the odds of a fall exacerbation. This indicates that these children with the greatest numbers of environmental allergies will have the greatest benefit on omalizumab and should be prioritized for treatment. These results add to a growing literature of “personalized” or precision medicine where biologic markers in a patient are used to precisely decide a specific treatment known to have the most benefit in that patient.
The Journal of Allergy and Clinical immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.