The rationale behind the use of anti-IgE therapy for food allergy is no different than for its use in other atopic conditions. By decreasing free serum IgE levels and downregulating the expression of the high-affinity IgE receptor, anti-IgE therapy should theoretically decrease IgE-dependent mast cell and basophil responses to ingested allergen as it does to inhaled allergens.
Data for the use of anti-IgE therapy in food allergy were first reported in 2003. In the initial trial, 84 peanut-allergic individuals, 12–64 years of age, were randomized to receive one of three doses (150, 300, and 450 mg) of a humanized, monoclonal anti-IgE antibody known as TNX-901 (also known as Hu-901) or placebo. All individuals had an entry double-blinded peanut challenge and a posttreatment open peanut challenge 2–4 weeks after completion of therapy. Treatment with TNX-901 increased the eliciting threshold dose of peanut at the posttreatment challenge in a dose-dependent manner; however, only the highest dose (450 mg) produced a statistically significant difference over placebo. Furthermore, the efficacy of this treatment was not uniform for individuals; although 25% of patients were able to tolerate over 20 peanuts following therapy, another 25% failed to develop any improvement in tolerance.
Omalizumab and Food Allergy
The promising results of the initial anti-IgE therapy in food allergy led to a double-blind trial of the currently commercially available anti-IgE antibody, omalizumab (Xolair; Genentech, South San Francisco, CA), in peanut allergy.[28••] In this trial, peanut allergic patients (6–75 years old) were randomized to receive either omalizumab or placebo in a 2 : 1 ratio. Unfortunately, this study was cut short due to the severity of two anaphylactic reactions during the baseline, qualifying peanut challenges (prior to the administration of any study drug). Only 14 individuals completed the trial up to that point (nine in the active arm and five in the placebo arm). Given that the study was initially powered to enroll 150 individuals, it is not surprising that the data did not reach statistical significance. However, as with the initial trial of anti-IgE therapy, omalizumab showed promising results suggesting that anti-IgE can increase the threshold dose required to elicit a reaction. When comparing the baseline tolerable peanut dose to the post-24 week treatment tolerable dose, there was a trend of increased peanut tolerability in the omalizumab-treated individuals compared with the placebo-treated individuals (P = 0.054). In addition,44%of the omalizumab-treated individuals were able to tolerate the goal dose of 1 g of peanut protein after 24 weeks of treatment compared with only one individual in the placebo-treated arm. Thus, it is possible that anti-IgE therapy could decrease the chances of an allergic reaction due to accidental ingestion, but it is unclear whether it could lead to tolerance.
Just as omalizumab has been used as an adjunctive therapy to increase efficacy and decrease adverse reactions with immunotherapy for respiratory allergy, there may be a role for its use as an adjunct to immunotherapy for food allergy. Although there are several promising reports on oral immunotherapy (OIT) for food allergy, this treatment is not without risks. Difficulties with oral and gastrointestinal side effects, as well as systemic allergic reactions have been reported with OIT. The addition of anti-IgE therapy to food immunotherapy may accelerate the desensitization process while minimizing adverse effects.
Preliminary results have now been published for one such study examining the use of omalizumab in a rush protocol of milk OIT.[31•] In this brief communication, the authors showed that treatment with omalizumab 7–11 weeks prior to initiating milk OIT allowed nine of the 11 enrolled individuals to tolerate the 1-day rush desensitization protocol going from 0.1 to 1000mg of milk protein. This was a pilot study, lacking a placebo group and baseline double-blinded milk challenge; however, it points to the potential use of omalizumab with food OIT, and there are now ongoing trials currently assessing the use of anti-IgE with OIT to various foods (Clinicaltrials.gov identifiers: NCT01157117,NCT00932282,NCT01290913).
Curr Opin Allergy Clin Immunol. 2012;12(3):293-301. © 2012 Lippincott Williams & Wilkins