New approaches for the treatment of anaphylaxis.

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Leung DY, Shanahan WR Jr, Li XM, Sampson HA

New approaches for the treatment of anaphylaxis.

Novartis Found Symp. 2004;257:248-60; discussion 260-4, 276-85.

PubMed ID
15025403 [ View in PubMed
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Abstract

Anaphylaxis represents the most extreme form of life-threatening allergic reactions. However, effective long-term therapies for this condition are not currently available. A number of potential approaches have proven effective in murine models of peanut-induced anaphylaxis and are currently being considered in humans, including the use of vaccines containing 'engineered' recombinant food proteins and Chinese herbal medications. TNX-901 is a humanized IgG1 anti-IgE mAb that recognizes and masks an epitope in the CH3 region responsible for binding to the high affinity Fc epsilon receptor (FcepsilonRI) on basophils and mast cells. Recently, we conducted a double-blinded, placebo-controlled, randomized, dose escalation trial in 84 patients with a history of peanut allergy. Allergy was confirmed and the threshold dose of encapsulated peanut established by a double-blinded, placebo-controlled oral food challenge (DBPCOFC) at screening. Patients were randomized 3:1 in three dose groups to receive either TNX-901 (150, 300 and 450 mg) or placebo subcutaneously every four weeks for four doses. They underwent a final open food challenge within 2-4 weeks after the last dose of study medication. From mean baseline values of 178-436 mg in the various treatment groups, the mean increases in the open food challenge threshold were 710, 913, 1650 and 2627 mg for the placebo, 150, 300 and 450 mg for TNX-901 dose groups, respectively (P = 0.0004, 450 mg vs. placebo; P = 0.0008 for trend with dose). TNX-901 was well tolerated. TNX-901 at a dosage of 450 mg significantly increased the threshold of sensitivity to peanut by open food challenge from a level of about half a peanut (178 mg) to almost nine peanuts (2805 mg). These studies suggest that treatment of patients with anti-IgE therapy may represent an effective long-term approach for management of food-induced anaphylaxis.

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