Anti-IgE may be an effective therapy for peanut allergy
At present, the only treatment for food allergy is specific food avoidance. However, a dramatic therapeutic approach to the treatment of this increasingly prevalent life-threatening disease has just been reported.
In this investigation, the effect of a humanized IgG1 monoclonal antibody against IgE (TNX-901) was analyzed for its efficacy in patients with peanut allergy.
This reagent binds with high affinity to an epitope in the CH3 domain of IgE and masks the region that is responsible for binding to both high and low affinity Fc epsilon receptors.
The investigators conducted a double-blind randomized dose-ranging trial in 84 patients with a history of immediate hypersensitivity reaction to peanut.
The patients, aged 12 to 60 years, were first subjected to a double-blind placebo-controlled food challenge in order to definitively establish the diagnosis of peanut allergy and to determine the threshold dose of encapsulated peanut, which elicited allergic reactions.
The patients were subsequently randomly assigned to three doses of a drug (150, 300, and 450 mg or placebo) delivered subcutaneously every four weeks for four doses.
Four weeks following the fourth dose, the patients underwent a final oral food challenge. Indeed, there was a significant increase in the amount of peanut protein exposure required to trigger an allergic response in the patients treated with anti-IgE antibody.
Importantly, the increase was related to the dose of the anti-IgE. For example, at the high dose of anti-IgE (450 mg) the oral food challenge threshold increased to 2,627 mg compared with 710 mg in the placebo group. This is a significant increase that may provide protection from a serious allergic reaction to a dose of allergen that would be expected from inadvertent exposures (e.g. from a threshold of approximately one-half of a peanut to almost 9 peanuts).
While there will be many hurdles (economic and clinical) to overcome before the eventual approval of anti-IgE for peanut allergy, these results represent significant and exciting opportunities for future therapy. They also provide definitive evidence that IgE-mediated pathways are indeed primarily responsible for peanut and probably other food allergen-induced immediate allergic reactions in humans.
Leung DYM et al. N Engl J Med 2003; 348:986-993.
