Omalizumab therapy in chronic spontaneous urticaria: pathogenic hypothesis and related cytokines

Omalizumab is an IgG-type monoclonal antibody against IgE and is the current third line approach to the treatment of severe chronic spontaneous urticaria (CSU) resistant to therapy with second generation antihistamines. Amongst the established mechanisms of omalizumab, down-regulation of high affinity FcERI is believed to be the main contributor to the action of the drug but takes place after no earlier than 80 days on the surface of mast cells and than 7 days on that of basophils following initiation of treatment. However, a reduction in CSU severity score following administration of omalizumab is commonly witnessed within the first week in up to 90% of patients (early responders) and even within the first 24 hours in the so-called “very early responders”. Such a rapid response may not be explained through omalizumab’s “classic” mechanisms of action and demands that other factors, acting as “fast mediators of autoimmunity”, be taken into account. The primary aim of this study was to define a cluster of cytokines in the serum of CSU patients that could be related to the clinical history of the disease, in terms of remission, resistance to therapy and relapse. The secondary endpoint was to investigate the potential role of these cytokines in the complex pathogenesis of CSU and in the modulation of response to omalizumab.