Changes in Total IgE Plasma Concentration Measured at the Third Month during Anti-IgE Treatment Predict Future Exacerbation Rates in Difficult-to-Treat Atopic Asthma: A Pilot Study

Abstract

In severe, difficult-to-treat atopic asthma with sensitization to perennial allergens, monoclonal antibodies directed against immunoglobulin E (IgE) are recognized to be clinically effective. Omalizumab, a recombinant monoclonal antibody, selectively binds to the high-affinity C-epsilon 3 site of human IgE and inhibits the inflammatory cascade in response to antigenic stimuli. Currently, no indicator is available for predicting patients’ responsiveness to long-term omalizumab treatment. This study aims to assess the relationship between early changes in plasma IgE concentration and major outcome variables over a 12-month course of omalizumab. Methods. Twenty-three nonsmoking, severe asthmatics (14 females; mean age 47.3 years ± 12.0 SD; mean BMI 25.8 kg/m2 ± 9.6 SD) sensitized to perennial allergens and unresponsive to high doses of common therapies were evaluated during a 12-month period of omalizumab treatment. Variables included total IgE plasma concentrations, Forced Expiratory Volume 1 second (FEV1) symptom complaints (Asthma Control Test (ACT) score), number of emergency visits, hospitalizations, and exacerbations. The Wilcoxon signed-rank test was used to compare changes observed after the 1-year omalizumab treatment versus baseline. Statistical modelization was used to determine possible relationships between changes in outcomes after 12 months and early changes in plasma IgE (after 3 months of treatment). Results. The number of emergency visits, hospitalizations, and exacerbations decreased (p < .004, p < .001, and p < .001, respectively) over the 12-months. In contrast, FEV1 and ACT score substantially increased (both p < .001); the ACT score reaching maximum after only 3 months. The S model showed the best fit and proved the strict relationship between the increase in IgE after 3 months and the exacerbation rate over the 1-year survey (threshold value of ≥250 IU/ml, p < .001). The improvement in FEV1 was independent of the increase in IgE. Conclusions. When confirmed on a larger population, early changes in IgE may be used as a predictor of future responders to omalizumab in terms of exacerbation rate, thus minimizing the economic burden of anti-IgE therapy.