Effect of anti-IgE therapy in patients with peanut allergy.
BACKGROUND
Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fc(epsilon) receptor on mast cells and basophils.


METHODS
We conducted a double-blind, randomized, dose-ranging trial in 84 patients with a history of immediate hypersensitivity to peanut. Hypersensitivity was confirmed and the threshold dose of encapsulated peanut flour established by a double-blind, placebo-controlled oral food challenge at screening. Patients were randomly assigned in a 3:1 ratio to receive either TNX-901 (150, 300, or 450 mg) or placebo subcutaneously every four weeks for four doses. The patients underwent a final oral food challenge within two to four weeks after the fourth dose.


RESULTS
From a mean base-line threshold 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<0.001 for the comparison of the 450-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 substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.
Leung
Donald Y M
DY
National Jewish Medical and Research Center, Denver, USA.
Sampson
Hugh A
HA
Yunginger
John W
JW
Burks
A Wesley
AW
Schneider
Lynda C
LC
Wortel
Cornelis H
CH
Davis
Frances M
FM
Hyun
John D
JD
Shanahan
William R
WR
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D021183:Peanut Hypersensitivity / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007073:Immunoglobulin E; C472419:talizumab