PEANUT ALLERGY:

Go to Summary of New Treatment of Peanut Allergy

1. Peanuts are a legume and are part of the peas, beans and soy family. They are actually not a nut but many peanut allergic patients are also nut sensitive. Most peanut allergic patients are not allergic to other legumes.
2. Peanut is a strong allergen but not every reaction is life-threatening. We cannot predict who will have a threatening reaction.
3. When children become allergic to a food, it is usually during the first two years of life, often the first time they are fed the food. After age 3 it is less common to become allergic to a food. Peanut sensitivity tends to persist.
4. Peanut allergy is common, almost as common as sensitivity to egg and milk. However peanut reactions can be threatening more often than reactions to milk or egg. Peanut is also commonly found in confectioneries and is a common foodstuff in North America. Children with asthma are at more risk of a serious reaction.
5. Occasionally children can outgrow sensitivity to peanut but this occurs less commonly than with milk and egg. If the skin test to peanut is negative then we test to several preparations of peanut and peanut butter itself. If the skin tests are negative we will confirm with a blood test and then go ahead with an oral challenge. It is worth evaluating in infancy to confirm the reaction, then school-age and finally in the teen years.
6. Pure peanut oils are not a problem but some oils (i.e. cold-pressed) are crude and contaminated with peanut protein which results in reactions in peanut-allergic individuals.
7. Some packages have a warning that the food may contain peanut. These are usually foods that are not intended to include peanut but are prepared in equipment that has been used to prepare other peanut-containing foods.
8. Caregivers must be taught the management of a peanut-allergic child and must be comfortable with the use of the EpiPen. When a reaction occurs, there should be no hesitation about administering the adrenaline and the child should be transported to an emergency department. It is safer to give adrenaline than not give it. Anti-histamines do not deal with the major symptoms of a reaction.

This is the phase 2 study of a treatment for peanut allergy. A phase 2 study is a small study to establish the safety of the drug and the effective dose. Because the phase 2 study gave positive results with no significant adverse effects, there is now a large multi-center phase 3 study underway. Successful completion of the phase 3 study will lead to the treatment becoming available.

In order to understand this abstract it is necessary to understand some basic allergy and immunology. First, IgE is the type of immunoglobulin that governs allergy. When an allergic individual becomes allergic to peanut, they make IgE antibody to the peanut allergen(s). This antibody sits on the surface of certain cells called Mast cells and Basophils. When the peanut allergic individual accidentally eats peanut, the peanut allergens are grabbed by the IgE antibody to peanut sitting on the cells. That causes the cells to release "mediators" like histamine that cause all the symptoms of anaphylaxis.

If something could prevent or block the IgE from sitting on the cells then the cells would not have anything on their surface that would be able to react with peanut allergens and therefore they would not release any mediators.

In this research a very special antibody to human IgE was created in the mouse. When this antibody is injected into humans, it binds to IgE in the humans including IgE that reacts with peanut. This mouse antibody prevents the human IgE from sitting on the Mast cells and Basophils. However when mouse protein (the mouse antibody to human IgE) is injected into a human, the human recognizes it as foreign and rejects it. So the mouse antibody has been modified so that when it is injected into humans it is not recognized as foreign and therefore is not cleared more rapidly from the human body. The monoclonal antibody binds to human IgE on the part of the IgE molecule that binds to the surface of Mast cells and Basophils and in that way prevents the IgE from binding to the cells.

In the present study, this modified mouse antibody to human IgE was tested at different doses for the ability to prevent reactions to peanut protein given to the peanut allergic subjects. The study involved 84 patients with a history of immediate reactions to peanut and the history was confirmed by oral challenge. The dose of peanut flour that would start a reaction to peanut was established by a double-blind, placebo-controlled oral food challenge. Three doses of the special modified mouse antibody to human IgE (150, 300, or 450 mg) or placebo were injected subcutaneously every four weeks for four doses. The patients underwent a final oral food challenge with peanut flour within two to four weeks after the fourth dose.

From a mean starting level 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 the modified mouse antibody to human IgE, 1650 mg in the group given 300 mg of modified mouse antibody to human IgE, and 2627 mg in the group given 450 mg of modified mouse antibody to human IgE (P<0.001 for the comparison of the 450-mg dose with placebo, and P for trend with increasing dose <0.001). The modified mouse antibody was well tolerated and did not create any more side effects than the placebo injection.

A 450-mg dose of modified mouse anti-human IgE significantly and substantially increased the amount of peanut flour that could be tolerated on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg). This is an effect that should translate into protection against most accidental ingestions of peanuts.

The clinical data confirmed the direct role of IgE in peanut-induced allergic reactions and demonstrate that the special modified mouse anti-human IgE, at a dose of 450 mg subcutaneously every four weeks, significantly increased the threshold of sensitivity to peanut antigen, as assessed by oral food challenge, to a level that should translate into at least partial protection against most unintended ingestions of peanut. Although these results are highly encouraging, the mouse antibody is still an experimental drug, and approval for general use will require confirmation of these results in additional studies i.e. a larger phase 3 study.