Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab)

Background: Although serological IgE measurements can aid in efficacy assessment of patients with asthma on omalizumab (Xolair [Genentech, Inc., South San Francisco, Calif]; humanized IgG ₁ antihuman IgE Fc), its effect on clinically used IgE assay performance is unknown. Objective: This study investigated the hypothesis that IgE:IgG-anti-IgE immune complex formation after omalizumab administration diminishes accuracy and increases variability of IgE assays performed in diagnostic immunology laboratories. Methods: Plasma from 4 atopic adults was incubated with omalizumab (50 or 200 molar excess to IgE) or buffer. Paired specimens were sent masked to 159 clinical laboratories in the College of American Pathologists Diagnostic Allergy Proficiency Survey (cycles SE-C-2003, SE-A-2005). Inhibitory effects produced by omalizumab on accuracy and reproducibility of US Food and Drug Administration (FDA)-cleared total and allergen-specific IgE assays were computed by using national proficiency survey data. Results: Total serum IgE levels measured in the 2 ImmunoCAP assays were minimally reduced (2.4-9.0%) by the presence of omalizumab, whereas 5 other assays showed marked reductions from 12.5% to 67.2% (P < .001) that increased in proportion to total serum IgE levels. The degree of interference was not large enough to produce detectable misclassification of IgE antibody results (positive to negative) in 4 multiallergen screening assays. Of 11 FDA-cleared IgE antibody assays, only 3 (ImmunoCAP, UniCAP, Immulite-2000) generated quantitative IU/mL results that could be assessed for interference. Omalizumab produced 0.8% to 27.8% reduction in allergen-specific IgE levels across 8 allergen specificities. Conclusion: Although as much as 62% loss in accuracy was observed in FDA-cleared human IgE assays, the ImmunoCAP system was sufficiently robust to provide accurate and reproducible total and allergen-specific IgE antibody results in a clinical setting where therapeutic levels of omalizumab are present in serum. Clinical implications: Accurate monitoring of total and allergen-specific IgE, together with free IgE levels, in serum from patients on omalizumab may help optimize dosing and maximize the efficacy of Xolair therapy.