Leung DYM, Sampson HA, Yuninger JW, et al. N Engl J Med. 2003;348:986–993
Purpose of the Study.
To determine whether subcutaneous administration of a humanized anti-immunoglobulin E (IgE) antibody, TNX-901, raises the threshold of sensitivity to peanuts among patients with peanut allergy.
Eighty-four patients between 12 and 60 years of age, with a history of allergic reactions to peanuts, total IgE levels between 30 and 1000 IU/mL, positive skin prick tests for peanuts, and documented reactions with formal peanut challenge at the start of the study, were studied.
A randomized, double-blind, placebo-controlled, dose-range study was performed. During the screening process, peanut allergy was confirmed and the threshold for reactivity was determined with a double-blind, placebo-controlled, oral food challenge with encapsulated peanut flour. Patients were subsequently randomized to receive subcutaneous injections of placebo or TNX-901 (150, 300, or 450 mg) at 4-week intervals, for a total of 4 doses. Two to 4 weeks after the final injection, a final peanut challenge was performed, to determine the threshold of reactivity to peanuts after the treatments. Serum samples were obtained at 4-week intervals, to monitor trough total IgE levels.
From mean baseline thresholds of sensitivity of 178 to 436 mg of peanut flour in the various groups, the mean increases in the oral food challenge threshold were 710 mg in the placebo group, 913 mg in the group given 150 mg of TNX-901, 1650 mg in the group given 300 mg of TNX-901, and 2627 mg in the group given 450 mg of TNX-901 (P < .001 for comparison of the 450-mg dose with placebo; P < .001 for trend with increasing dose). Patients who received 450 mg had a mean threshold of reactivity of 2805 mg of peanut protein (equivalent to ∼9 peanuts), compared with 178 mg (equivalent to one half of a peanut) before the injections.
Subcutaneous administration of TNX-901 increases the threshold of reactivity to peanuts in a dose-dependent manner, which may translate into protection against most accidental ingestions of peanuts.
Peanut allergy is one of the most serious food allergies, in terms of severity of reactions and persistence of hypersensitivity. Approximately 50 to 100 people die each year in the United States as a result of unintended peanut ingestion. This well-designed and well-conducted study demonstrates that subcutaneous TNX-901 injections decrease total IgE levels in the blood and raise the threshold of sensitivity to peanut protein, in a dose-dependent manner. Impressively, 24% of patients who received the 450-mg injections were able to tolerate up to 8 g of peanut protein without reactions. This increase in the threshold for reactivity could help prevent reactions to accidental peanut ingestion, but regular injections are required to maintain the elevated threshold. Such a treatment strategy, although expensive, might reduce the number of reactions to accidental peanut ingestion until more definitive disease-modifying therapies are developed. Unfortunately, TNX-901 is not available for treatment at this time and the humanized anti-IgE antibody Xolair (Genentech, South San Francisco, CA), which is now Food and Drug Administration-approved for use in asthma, has not been studied for similar benefits in peanut allergy.