News, Views, & Reviews

Chronic Urticaria: Omalizumab and Review of Therapeutic Options

June 2013 | Volume 12 | Issue 6 | Feature | 715 | Copyright © 2013

Kendra Gail Bergstrom MD FAAD

Abstract

Chronic idiopathic urticaria is a rare but significantly life-altering skin disease. Recent developments in immunology have promoted our understanding of its autoimmune pathology, but treatment options have not yet developed at the same pace. When antihistamines aren't sufficient, the next steps for treatment have less evidence for support. Fortunately, a Phase III clinical trial has shown that the monoclonal antibody omalizumab, approved for use in asthma, can reduce symptoms of chronic idiopathic urticaria when added to maximal doses of H1-antihistamines. Therapeutic options for chronic idiopathic urticaria are reviewed.

J Drugs Dermatol. 2013;12(6):715-716.

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While rare, chronic idiopathic urticaria is a cause of significant suffering and morbidity for those affected. Formally, chronic urticaria is defined as lasting longer than six weeks. In practice, many people suffer for months or years. While an underlying etiology can sometimes be found, in over 50% of cases the cause remains obscure and is labeled chronic idiopathic urticaria (CIU). The identification of the IgG anti-Fc epsilon R1 antibody helped to understand the etiology of chronic idiopathic urticaria up to 60% of cases.1 Individuals with the receptor antibody generally have a longer disease course and are less likely to have an underlying treatable cause for urticaria. Treatment options are few and most are used as off-label indications. However, this discovery has not yet affected therapeutic options.

Therapeutic Options for Chronic Idiopathic Urticaria

  • H1 antihistamines, both sedating and non-sedating
  • H2 histamine antagonists: cimitidine, ranitidine, famotidine
  • Tricyclic antidepressant: doxepin2
  • Calcium channel blocker: nifedipine3
  • Leukotriene receptor antagonists: montelukast, zafirlukast4
  • oral corticosteroids
  • Inosine monophosphate dehydrogenase inhibitor: mycophenolate mofetil5
  • Calcineurin inhibitor: cyclosporine (may be effective at doses < 3 mg/kg daily)6
  • methotrexate
  • Intravenous immunoglobuin, IVIg
  • Case reports: plasmaphoresis, cyclophosphamide
  • Monoclonal antibody: omalizumab
  • In pregnancy: chlorpheniramine, diphenhydramine7

The use of sedating and non-sedating H1 antihistamines for all types of urticaria is well established. Doses much higher than those approved by the FDA, usually 2 to 4 times higher, is often needed for control of CIU. While dosing regimens vary, many physicians treat morning and evening with the FDA approved dose of antihistamine then titrate upwards to control of disease or until side effects occur. While the side effects of antihistamines may vary, the most common are dry mucous membranes, anticholinergic symptoms including tachycardia, urinary retention, and blurry vision, and exacerbation of narrow-angle glaucoma. It is important to note that all studies used the above agents in addition to maximally tolerated doses of antihistamines.

H2 Histamine Antagonists

Because basophils have H2 receptors that mediate histamine release, the use of H2 antihistamines has a plausible mechanism for efficacy. Their relatively safe toxicity profile and there is a paucity of clinical data to support their use other than as an adjunct. One study in 2002 showed famotidine to be as effective as diphenhydramine for acute urticaria among a group of twenty-five patients an emergency department setting. Given that these patients received intramuscular medications within 72 hours of the onset of acute urticaria, it is harder to apply this data for treating CIU.

The most recent retrospective case series using an H2 antagonist for CIU was in 2013 in Japan.9 The authors did show subjective efficacy of a newer second generation H2 antagonist, lafutidine, added to antihistamines over a three month period. Seventy-five percent of a group of 46 patients showed improvement at three months after adding lafutidine; no adverse events were reported. Lafutidine is a second-generation H2 antagonist currently available in Japan, China, and India; dose is 10 mg given once or twice daily.

Leukotriene Receptor Antagonists: Montelukast, Zafirlukast

Leukotrienes are signaling molecules from the arachadonic acid inflammatory pathway. Leukotriene receptors are present on mast cells and cause mast cell degranulation and histamine release. While originally developed for asthma, the leukotriene receptor antagonists montelukast and zafirlukast have shown efficacy in urticaria as well. Dosing is daily for both medications, and adverse events are rare. Response rates in published studies4,10range from 30 to 50 percent, though it may be higher among patients with more recalcitrant disease.10

Nifedipine

Publications in the 1980s and 1990s supported the use of nifedipine to treat chronic idiopathic urticaria. Studies of patients with active CIU on maximally tolerated doses of antihistamines were studied

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