Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma

Abstract

The clinical efficacy of omalizumab has been optimised through the development of an individualised dosing table that emerged from an understanding of the pharmacodynamics of this agent.

Anticorpo monoclonal anti-IgE no tratamento da asma e de outras manifestações relacionadas a doença alérgica

“…On the other hand it had to be inactive with respect to IgE bonded to high-affinity receptors (FcεRI) fixed in the surface of basophil and mast cell membranes, and also should not recognize IgE bonded to low-affinity receptors (FcεRII or CD23), which are abundantly distributed across several different types of cell. [8][9][10][11] Tests with laboratory animals and clinical trials corroborated these properties, which had been established as goals for the molecular engineering that resulted in the synthesis of omalizumab. [9][10][11] Omalizumab, as a nonanaphylactic synthetic antibody, Table 2 -Total recommended 4 week omalizumab dosages, according to total serum IgE levels and body weight.…”

“…[8][9][10][11] Tests with laboratory animals and clinical trials corroborated these properties, which had been established as goals for the molecular engineering that resulted in the synthesis of omalizumab. [9][10][11] Omalizumab, as a nonanaphylactic synthetic antibody, Table 2 -Total recommended 4 week omalizumab dosages, according to total serum IgE levels and body weight. The medication is packaged in 150 mg phials and no more than 150 mg should be given per injection site, neither should more than 300 mg be given on a single day.…”

“…These levels are maintained with continued application of the product. 10 In human beings, the product is very well tolerated by the majority of patients, permitting an accentuated drop in total free serum IgE concentration for 4 to 6 weeks, due to its extended half-life with a single subcutaneous injection.…”

Effect of antigen binding affinity and effector function on the pharmacokinetics and pharmacodynamics of anti-IgE monoclonal antibodies

“…3 Individuals with high pre-treatment IgE levels (> 700 IU/mL) or those with higher body weights (> 150 kg) often require multiple omalizumab injections or do not qualify for therapy because the dosage required would be too high. 4 Due to these limitations, development of a higher-affinity antiIgE molecule offers the potential to reduce the dose required to suppress free IgE levels and may allow treatment of asthmatic individuals not eligible to receive omalizumab therapy.…”

“…1 Clinical benefit with omalizumab has been demonstrated when free IgE levels are reduced to less than 20 IU/mL in asthmatic patients. 3 To achieve a clinically meaningful reduction of pre-formed anti-IgE:IgE immune complexes was performed in mice because this species was used extensively in assessing the clearance mechanisms utilized for omalizumab:IgE and the model has been well-characterized. 10 We chose the cynomolgus monkey to evaluate the PK and PD of HAE1 and HAE2 because both bind to cynomolgus IgE with similar affinity compared with that observed for human IgE, 5 and omalizumab and IgE are known to form complexes of various sizes in cynomolgus monkey.…”