Effect of Anti-IgE Therapy in Patients with Peanut Allergy
Donald Y.M. Leung, M.D., Ph.D., Hugh A. Sampson, M.D., John W. Yunginger, M.D., A. Wesley Burks, Jr., M.D., Lynda C. Schneider, M.D., Cornelis H. Wortel, M.D., Ph.D., Frances M. Davis, Ph.D., John D. Hyun, B.S., William R. Shanahan, Jr., M.D., for the TNX-901 Peanut Allergy Study Group
Background Peanut-induced anaphylaxis is an IgE-mediated conditionthat is estimated to affect 1.5 million people and cause 50to 100 deaths per year in the United States. TNX-901 is a humanizedIgG1 monoclonal antibody against IgE that recognizes and masksan epitope in the CH3 region of IgE responsible for bindingto the high-affinity Fc receptor on mast cells and basophils.
Methods We conducted a double-blind, randomized, dose-rangingtrial in 84 patients with a history of immediate hypersensitivityto peanut. Hypersensitivity was confirmed and the thresholddose of encapsulated peanut flour established by a double-blind,placebo-controlled oral food challenge at screening. Patientswere randomly assigned in a 3:1 ratio to receive either TNX-901(150, 300, or 450 mg) or placebo subcutaneously every four weeksfor four doses. The patients underwent a final oral food challengewithin two to four weeks after the fourth dose.
Results From a mean base-line threshold of sensitivity of 178to 436 mg of peanut flour in the various groups, the mean increasesin the oral-food-challenge threshold were 710 mg in the placebogroup, 913 mg in the group given 150 mg of TNX-901, 1650 mgin the group given 300 mg of TNX-901, and 2627 mg in the groupgiven 450 mg of TNX-901 (P<0.001 for the comparison of the450-mg dose with placebo, and P for trend with increasing dose<0.001). TNX-901 was well tolerated.
Conclusions A 450-mg dose of TNX-901 significantly and substantiallyincreased the threshold of sensitivity to peanut on oral foodchallenge from a level equal to approximately half a peanut(178 mg) to one equal to almost nine peanuts (2805 mg), an effectthat should translate into protection against most unintendedingestions of peanuts.
Source Information
From the National Jewish Medical and Research Center, Denver (D.Y.M.L.); Mount Sinai School of Medicine, New York (H.A.S.); Mayo Clinic, Rochester, Minn. (J.W.Y.); Arkansas Children's Hospital, Little Rock (A.W.B.); Children's Hospital, Boston (L.C.S.); ClinQuest, Marlborough, Mass. (C.H.W.); and Tanox, Houston (F.M.D., J.D.H., W.R.S.).
Address reprint requests to Dr. Sampson at the Department of Pediatrics, Box 1198, Mount Sinai School of Medicine, 1 Gustave L. Levy Pl., New York, NY 10029-6574, or at hugh.sampson{at}mssm.edu.
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