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

Current therapies for seasonal allergic rhinitis (SAR) 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 + 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
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