The results of the first of three phase III clinical trials of the effects of omalizumab in patients with chronic idiopathic urticaria were reported online in the New England Journal of Medicine this week.
Urticaria (‘hives’) occurs when mast cells in the skin are triggered to release histamine and other inflammatory mediators stored in cytoplasmic granules (‘degranulation‘). In acute urticaria due to allergic reactions, degranulation is triggered when allergen is bound by IgE antibodies attached to FcεRI receptors on the mast cell surface. However, chronic urticaria is not IgE mediated and the mechanism by which mast cells are triggered to degranulate and release histamine is not known.
Omalizumab is a recombinant ‘humanized’ monoclonal antibody which binds rapidly to circulating IgE, inhibiting its attachment to FcεRI receptors on basophils and mast cells. Expression of FcεRI receptors in basophils is downregulated within 2 weeks, and within 8 weeks there is reduced FcεRI expression and degranulation by tissue mast cells.
In this trial, patients with chronic idiopathic urticaria who remained symptomatic despite treatment with H1-antihistamines were randomized to receive three subcutaneous injections at monthly intervals with either omalizumab 75 mg, 150 mg, 300 mg, or placebo.
Dietary testing to determine whether there were underlying food chemical intolerances was not performed.
There was a dose-dependent reduction in symptom scores which lasted for 4 weeks after the last injection, after which scores gradually returned to baseline levels. It was concluded that omalizumab does not modify the underlying disease process.
Adverse events attributed to the study drug occurred in 4-9% of participants. The place of omalizumab in the management of patients with chronic urticaria remains to be determined.