1.1. Disease Prevalence and Incidence

Chronic idiopathic urticaria (CIU), also referred to as chronic spontaneous urticaria, is characterized by the presence of itchy hives, angioedema, or both, lasting for a period of six weeks or longer with no identifiable external cause.^1–4 The average duration of CIU is between one and five years, with a longer duration in more severe cases, cases with concurrent angioedema, cases in combination with physical urticaria, or cases with a positive autologous serum skin test.³ Although CIU can manifest at any age, the peak incidence rate is among individuals between 20 and 40 years of age.^1,3 The prevalence of CIU has been reported to be 0.5% to 1.0% in the overall population, with a twofold higher incidence in women than in men.^1,3,4 Available data suggest that 33% to 67% of patients with CIU exhibit both hives and angioedema, 29% to 65% exhibit only hives, and 1 to 13% exhibit only angioedema.³

The pathogenesis of CIU is not completely understood but may be associated with histamine release from cutaneous mast cells and blood basophils.¹ Approximately one-third of patients will test positive on the autologous serum skin test, indicating the presence of autoantibodies or histamine-releasing factors, and some patients test positive for autoantibodies to the immunoglobulin E (IgE) receptor or IgE in the basophil histamine-release assay, or both.¹

1.2. Standards of Therapy

The goal of CIU management is to achieve complete symptom control of hives. The first approach is to identify and eliminate underlying causes or eliciting triggers, and the second is pharmacotherapy aimed at providing symptom relief.^3,6,10

Identifying and eliminating the underlying cause is the most desirable option, but this may not be applicable in many cases of CIU.³ Studies have reported successful identification of possible underlying causes of CIU in 0% to 43% of patients.³ Identifying underlying causes often requires a broad spectrum of investigative procedures from specialized centres.³

Pharmacological treatments aim to reduce the effect of mast cell mediators such as histamine, platelet-activating factor, and others on target organs. International guidelines on the management of urticaria were developed by a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum, and the World Allergy Organization with participating delegates from 21 national and international societies.^5,6 The Allergy 2014 guidelines recommend non-sedating second-generation H₁ antihistamines as first-line treatment of CIU for adults and children. Older first-generation antihistamines have anticholinergic sedative effects that make them unsuitable for use both in adults and, especially, in children. For patients not responding adequately to the recommended dose of second-generation H₁ antihistamines after two weeks, the dose can be increased up to fourfold. If symptoms persist after one to four further weeks of treatment at a fourfold dose of second-generation H₁ antihistamines, add-on therapy using omalizumab (OMA), cyclosporin A, or the leukotriene receptor antagonist (LTRA) montelukast should be considered. The clinical expert consulted for this review indicated that H₂ antagonists (e.g., ranitidine) are also commonly prescribed for patients with inadequate response to H₁ antihistamines, although the aforementioned international guidelines do not recommend their use.^5,6 A short course of corticosteroids up to a maximum of 10 days may be used to manage exacerbations, but long-term use of systemic corticosteroids is not recommended.

Approximately 50% of CIU patients will continue to experience symptoms despite treatment with standard doses of H₁ antihistamines.³ Although higher doses are often used, side effects such as drowsiness may limit the ability to reach sufficient doses to achieve full resolution of hives.

The only Health Canada–approved drugs for the treatment of CIU are H₁ antihistamines (i.e., cetirizine, loratadine, desloratadine, and fexofenadine) and OMA.

1.3. Drug

OMA is a humanized, recombinant, immunoglobulin G, anti-IgE monoclonal antibody that binds to IgE and prevents it from binding to its high-affinity receptor on mast cells and basophils, thereby reducing IgE-induced mast cell and basophil degranulation and the release of histamine.¹ For CIU, OMA is administered subcutaneously by a health care provider every four weeks at a dose of 150 mg or 300 mg. OMA is available as a lyophilized, sterile powder in a single-use 5 mL vial designed to deliver 150 mg of OMA for subcutaneous administration upon reconstitution with 1.4 mL sterile water for injection.

OMA was previously reviewed by the Canadian Expert Drug Advisory Committee (CEDAC, now the Canadian Drug Expert Committee [CDEC]) in March 2006 for the treatment of moderate to severe persistent asthma in adults and adolescents aged 12 years or older whose symptoms are inadequately controlled with inhaled corticosteroids, and received a recommendation of “do not list.”¹¹

Table 2

Key Characteristics of Omalizumab and Second-Generation H₁ Antihistamines.