Xolair: Not Just for Asthma

Gary J. Stadtmauer, MD

Disclosures Jan 04, 2013

Introduction

Humanized monoclonal IgG anti-IgE is an effective biologic agent that has been in use for more than a decade to treat atopic asthma. The effect of omalizumab (Xolair®) IgE reduction alone from might explain why it alleviates respiratory allergy, but omalizumab has also been found to be effective for a range of other conditions through its other mechanisms of action.

For example, after just 3 months of treatment, the reduction in functional IgE leads to a more than 95% downregulation of the IgE receptor. ^[1]This is seen in mast cells, basophils, and dendritic cells, which can explain the attenuation of the IgE-mediated response to allergens. The decreased antigen processing also results in less antigen presentation to Th2 cells -- hence, less cytokine stimulation of eosinophils. The clinical implications of this immunomodulation were highlighted in an excellent article by Sanchez and colleagues, ^[1]which should be read by clinicians as a classic bench-to-bedside review.

Omalizumab and Chronic Urticaria

Although the most frequent adverse effect of omalizumab administration is urticaria that did not dissuade some from using this drug to treat chronic idiopathic urticaria -- with success. Numerous case reports (as well as this author's experience) ^[2]support the efficacy of Xolair in chronic idiopathic urticaria. There are, however, no controlled trials to back these findings. Nonetheless, patients with various forms of urticaria, including autoimmune and idiopathic varieties of chronic urticaria as well as physical urticarias (cold, solar, and delayed pressure), have been reported to respond to omalizumab. Many of the studies were case reports, but a study of 12 patients with urticaria found that 7 of them responded within 4 months of treatment with omalizumab. ^[3]The mechanism of action in these cases is proposed to be the effect of omalizumab on basophil and mast cell survival rather than its effect on IgE, which was low in some cases.

Atopic Dermatitis

At the opposite end of the total serum IgE spectrum are many patients with eczema, whose serum IgE level often exceeds 1000 kU/L -- greater than the threshold for Xolair dosing. A few cases of response to omalizumab monotherapy have been reported, but the only blinded, placebo-controlled trial was very small and did not yield positive results. ^[4]

Idiopathic Anaphylaxis and Mastocytosis

IgE and the IgE receptor have been implicated in the pathogenesis of idiopathic anaphylaxis. Successful treatment of idiopathic anaphylaxis with omalizumab has been reported and is now the subject of an National Institutes of Health study. Although the mechanism of anaphylaxis is different than that of idiopathic anaphylaxis, mastocytosis-related anaphylaxis has also responded to Xolair in a few cases.

Omalizumab and Food Allergy

Patients receiving omalizumab for asthma have noted increased tolerance of foods that had previously caused IgE-mediated reactions. Controlled trials with food challenges have yet to be done. Studies of Xolair and eosinophilic gastrointestinal diseases are now under way.

Nonatopic Conditions

Omalizumab has worked as both monotherapy and as rescue therapy in refractory cases of Churg-Strauss syndrome. The impact of anti-IgE on allergic bronchopulmonary aspergillosis is unclear. Although it reduces total and Aspergillus-specific IgE levels, omalizumab has not been shown to improve clinical outcomes. Serum IgE is a marker of allergic bronchopulmonary aspergillosis activity, but if blocking IgE does not help then it would seem to only hinder monitoring of the disease state. Of note, a patient with Menière disease and mastocytosis experienced improvement in both conditions when treated with Xolair.

Conclusion

Over time, additional clinical applications for omalizumab will be identified. For less common conditions, it will be hard to conduct the proper trials to gain US Food and Drug Administration approval. The greatest obstacle may be cost of the drug. Some insurers will pay for Xolair on a case-by-case basis for chronic urticaria. And Genentech's Xolair Access Solutions has also been very supportive of doctors and patients who are unable to obtain coverage for nonasthmatic conditions.