Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria

Abstract

The monoclonal anti-immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite H1 -antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically 'abnormal' IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU.

Keywords: chronic idiopathic urticaria; chronic spontaneous urticaria; omalizumab.

Conflict of interest statement

Conflict of interests

Allen P. Kaplan is a consultant for Novartis/Genentech, and he also adjudicates allergic reactions due to antihypertensive agents and drugs for diabetes for Novartis. Ana M. Giménez-Arnau is a medical advisor for Uriach Pharma, Genentech, and Novartis. She has received research grants from Intendis—Bayer, Uriach Pharma, and Novartis and has participated in educational activities sponsored by Uriach Pharma, Novartis, Genentech, Menarini, GSK, MSD, Almirall, and Leo Pharma. Sarbjit S. Saini has received grant support from the National Institutes of Health, Novartis, and Astra-Zeneca; he is a consultant to Genentech, Medimmune, Novartis, Ono Pharma, and Regeneron.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Figure 1

Time course of known cellular and clinical effects of omalizumab identified in studies focused on (A) patients with allergic response, mast cell diseases and (B) chronic urticaria. *MacGlashan et al. (2013) observed a 2.5- to 125-fold increase in basophil sensitivity after omalizumab treatment with sensitivity shifts noted at the midpoint and after 12 weeks of treatment.