The recoveryELISA--a newly developed immunoassay for measurement of therapeutic antibodies and the target antigen during antibody therapy.

Therapeutic antibodies are an important part of Biopharmaceuticals. They are highly innovative and specific drugs. Additionally, they play a challenging role in new demands in diagnostics because they disturb conventional antibody-based tests, such as immunoassays. The recoveryELISA is a newly developed immunoassay technology for monitoring such therapeutic antibodies or comparable biologics during the therapy. The recoveryELISA determines three results in one test: the free level of antigen (if available in serum), the level of therapeutic antibody and the specific dose-response interaction. The free level of antigen is the amount that can be measured in the immunoassay, as it exists unmasked under assay conditions. The relationship between therapeutic antibody level and neutralization rate of target protein is shown by the so-called 'recovery curve'. The recoveryELISA is demonstrated with the example of Omalizumab/IgE.

Monitoring free serum IgE in severe asthma patients treated with omalizumab.

BACKGROUND: Benefit of treatment with the monoclonal anti-IgE-antibody omalizumab in severe IgE-dependent asthma requires a significant reduction of serum free IgE concentrations. It is unclear if monitoring free serum IgE is clinically meaningful once omalizumab treatment is initiated. METHODS: Free IgE and omalizumab serum concentrations were quantified in 22 patients with severe asthma (68% female, 47 ± 11 yrs, mean (±SD) pre-bronchodilator FEV(1) 62 ± 13%, baseline mean (±SEM) free serum IgE 652 ± 136 ng/ml) treated with omalizumab for 4 months using a Recovery-ELISA. RESULTS: Omalizumab treatment reduced free serum IgE prior to the second omalizumab injection by 73%, after 16 weeks by 81% to 58 ± 12 ng/ml (p < 0.001 vs. baseline). 17 patients responded to anti-IgE therapy as judged by physician-rated global evaluation of treatment effectiveness. There was neither a relation between free serum IgE concentrations and treatment response nor a significant or clinically relevant correlation between free IgE levels and changes in lung function, exhaled NO, asthma control, and quality of life. Serum concentrations of omalizumab were detected in all patients and reached a stable phase within 8 weeks. CONCLUSIONS: Monitoring free IgE and omalizumab serum concentrations in patients treated with omalizumab does not predict clinical response nor does it add to the decision to continue or stop treatment. However, routine measurements of free IgE may be clinically relevant to demonstrate an adequate reduction in free IgE in patients not responding to omalizumab therapy.