Efficacy and Safety Evaluation of Allergen Immunotherapy Co-Administered with
Omalizumab, an anti-IgE Monoclonal Antibody

Principal Investigator:
Thomas B. Casale, Creighton University School of Medicine

Abstract | Investigators | Background | Resources | Publications

Abstract

Current therapies for seasonal allergic rhinitis include allergen avoidance, pharmacologic interventions such as antihistamines, sympathomimetics, topical and systemic corticosteroids, and chromones and immunotherapy. Although pharmacologic agents are effective for some patients, their role is limited by their inability to completely relieve symptoms, and in some cases, the induction of deleterious side effects. Immunotherapy (IT) regimens can be highly effective in controlling symptoms of SAR and can offer advantages over pharmacotherapy for those patients who have symptoms that are refractory to medications or those who cannot tolerate the side effects. However, traditional IT is associated with the risk of allergic reactions to the extract injections and its effectiveness for allergic respiratory disorders is not always evident.

Allergic diseases are mediated by IgE and Th2-type immune responses, which are opposed by Th1-like responses. Omalizumab (anti-IgE) reduces IgE levels thereby leading to decreased FcER1 and CD23 expression on key immune effector cells. These and other changes evoked by omalizumab cause a blunting of allergic respiratory symptoms. In a recent clinical trial, the combination of omalizumab + immunotherapy (IT) produced a greater reduction in symptoms than IT alone. However, the omalizumab was added to existing IT. This study will examine omalizumab as a pretreatment to IT to condition the recipient in an attempt to suppress Th2-like responses.

Specifically, this study will:

1. examine whether anti-IgE (omalizumab) given 9 weeks prior to rush IT (RIT) followed by 12 weeks of dual anti-IgE + IT is safer and more effective than anti-IgE alone, RIT alone or placebo in preventing the symptoms of ragweed-induced SAR;
2. study the immunologic mechanisms of action associated with these therapies; and
3. study whether there is induction of tolerance after discontinuing these therapies as manifested by persistent inhibition of in vivo challenges and prolonged in vitro immunologic changes indicative of immune tolerance.
   

Participating Investigators

	Thomas B. Casale, Creighton University Medical School, Omaha, NE
	William Busse, University of Wisconsin, Madison WI
	Joel Kline, University of Iowa, Iowa City, IA

Background Articles

	Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial - JAMA [PubMed]
	Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis - J Allergy Clin Immunol [PubMed]

Resources & Interesting Links

FDA Briefing on Omalizumab safety [go]

Study Publications

	Casale, TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, Mokhtarani M, Seyfert-Margolis V, Asare A, Bateman K, Deniz Y, Immune Tolerance Network. Omalizumab Pretreatment Decreases Acute Reactions Following Rush Immunotherapy for Ragweed-Induced Seasonal Allergic Rhinitis. J Allergy Clin Immunol 117: 134-140, 2006. [PubMed] [Reprint]
	Francis JN, Klunker S, Seyfert-Margolis V, Asare A, Casale T, and Durham SR (2006): Combination treatment with Omalizumab and rush immunotherapy for ragweed allergic rhinitis: induction of inhibitory antibody responses.  J Allergy Clin Immunol, (in press).