Clinically significant variability of serum IgE concentrations in patients with severe asthma.
Journal of Asthma 2012; 49(2):115-20
Mummadi SR MBBS1 , Hatipoğlu US MD1 , Gupta M MBBS2 , Bossard MK RRT, AE-C1 , Xu M MS3, Lang D MD1
1 Respiratory Institute, Cleveland clinic, Cleveland Ohio, USA
2 Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland Ohio USA
3 Quantitative Health Sciences, Cleveland Clinic, Cleveland Ohio USA
Objective: To determine the magnitude of immunoglobulin E (IgE) variability in a cohort of patients with severe asthma considered for omalizumab therapy.
Methods: Retrospective chart review identified 65 patients with two or more IgE determinations out of the 124 patients referred to the Cleveland Clinic Respiratory Institute for treatment with omalizumab from 2003-2011. Patients with conditions known to affect IgE levels were excluded. Demographic data, pulmonary function testing, medications, smoking status, and atopy were recorded. The range of variability and percent variability in relation to baseline serum IgE were calculated.
Results: The median difference of serum IgE between the minimal and maximal values was 94.9 IU/mL (IQR 26.3-324.1 IU/mL). Percent variability from minimum value had a median of 75.5% (IQR 23.3-152.6%). There was no correlation between age, body mass index, lung function and IgE variability. Greater variability was associated with female gender (p= 0.06). There was no association with peripheral eosinophilia, prednisone use and leukotriene modifier use at presentation. The magnitude of the variability would have affected omalizumab dosing in 20 out of 42 patients. Six patients who may have qualified at different time points would not have been deemed candidates based on an IgE level < 30 IU/ml or > 700 IU/ml.
Conclusion: Serum IgE concentration may have clinically significant variability over time, which would affect candidacy for anti-IgE treatment and dosing. Our findings imply that repeating serum IgE determinations merits consideration for patients whose initial levels are 700 IU/mL. Prospective studies are warranted to delineate the factors that contribute to IgE variability.
Severe asthma refractory to conventional treatment affects an estimated 5% of patients with asthma1. Anti-IgE therapy with omalizumab is a therapeutic option for these patients who remains symptomatic despite maximal treatment. Candidacy for treatment and dosing are contingent upon the concentrations of serum IgE. Furthermore, due to lack of safety and efficacy data, patients whose IgE levels < 30 IU/ml or > 700 IU/ml are excluded from receiving the drug.
We wondered whether serum IgE has longitudinal variability in this subset of patients with severe asthma. Physicians in the pulmonary and allergy field at the notion that IgE level is constitutionally determined and does not change by much in individuals. Certainly, there are a multitude of medical conditions where IgE concentration fluctuates and is important in pathophysiology of the disorder e.g. allergic bronchopulmonary aspergillosis, eosinophilic pneumonia etc. We decided to review all of the patients were referred to our center for the treatment of severe refractory asthma with omalizumab therapy for the past determinations of total IgE level. We have identified 65 patients out of 124 who had had multiple IgE determinations for various reasons. Common scenarios for this to happen were insurance denial for reimbursement of omalizumab or patient choice not to receive the drug on the first visit followed by a return to the clinic when these issues resolved. Physicians under those circumstances ordered second, sometimes third requests for IgE level determination. There was a careful chart reviewed to exclude conditions associated with elevated IgE as alluded to, previously. We also made sure that the patients were not on omalizumab therapy at or near the time of IgE level determination, since some assays are unable to differentiate between omalizumab-IgE complex and IgE molecule. Patients who were receiving allergen immunotherapy were also excluded.
The results are displayed in 2 figures that represent patients who had IgE levels 1000IU/ml (figure 2) for easier discrimination. As is apparent to the naked eye, there is significant variability in IgE levels that are obtained at different time intervals in some patients. Mean time interval between determinations was 2 years.
These findings have important clinical implications. Had these patients received omalizumab therapy, the differences in IgE level may have resulted in dosing changes in nearly half of the patients. One in 6 patients may have been disqualified for omalizumab treatment since they were outside the 700 IU/mL boundaries.
In addition to the obvious clinic ramifications of these findings i.e. dose adjustment and treatment candidacy issues at different time points of testing, the variability in IgE which is present in only a subgroup of severe asthma patients, may define an asthma phenotype. Although we did not find significant correlation between age, body mass index, lung function, peripheral eosinophilia and corticosteroid use, we feel further study is required to answer these questions .
1. Proceedings of the ATS Workshop on Refractory Asthma. Current Understanding, Recommendations, and Unanswered Questions. Am J Respir Crit Care Med. 2000;162(6):2341–51.