Does an anti-IgE antibody work as a treatment for asthma? 

A particular antibody, immunoglobulin E or IgE, is thought to be critical in causing allergic reactions. People predisposed to allergies make this antibody in response to exposure to certain allergens, like cat dander, house dust mite, and certain plant pollens. The antibody then binds to mast cells in the tissues lining the nose and bronchi, and also in the skin. On re-exposure to the allergen, the allergen is bound to the IgE antibody on the surface of the mast cell.  This triggers the mast cell to release a number of potent chemicals, like histamine, that cause airway smooth muscle contraction, tissue swelling, mucus secretion, and other changes that lead to narrowing of the airways and the symptoms of chest tightness, wheezing, shortness of breath, and coughing.

Using modern techniques of molecular biology, Genentech has produced an anti-IgE antibody. That is, they have made an antibody that attacks the IgE antibody that is thought to be fundamental to causing allergic diseases. Think of it as a kind of anti-missile missile.

To find out whether this new, highly specific approach to treatment is actually effective, we examined how giving the anti-IgE antibody (called E25) affected the reactions to allergen inhalation in 18 volunteers with allergic asthma. All the volunteers had two allergen challenges: one at the beginning of the study, and the second after ten weeks of treatment with a placebo or with the anti-IgE antibody, E25.

Our results showed that the volunteers who received E25 had no side effects from it and showed large reductions in their reactions to allergen inhalation. The intensity of the immediate reaction was reduced by more than 50%. The intensity of the late reaction (occurring between 2 and 6 hours after inhaling allergen) was reduced by more than 75%. The volunteers receiving active treatment also showed a reduction in the overall reactivity of their airways (that is, their bronchial reactivity diminished) and a reduction in the number of eosinophils in their sputum.

These results confirmed the promising results from tests of this anti-IgE treatment in laboratory animals, and suggest that it may have an anti-inflammatory effect.

For details on this study, please see the published manuscript in American Journal of Respiratory and Critical Care Medicine 1997;155:1828-1834.

The effect of an anti-IgE monoclonal antibody on the early and late phase responses to allergen inhalation in asthmatic subjects. Fahy JV, Fleming HE, Wong HH, Liu JT, Su JQ, Reimann J, Fick RB, Boushey HA.

After showing that E25 treatment reduces the response to allergen challenge in allergic volunteers, the next step is to find out if it actually helps people with moderately severe or severe asthma. We participated with twelve other research centers in giving E25 or placebo to about 300 volunteers with asthma severe enough to require high doses of inhaled steroids or oral doses of prednisone.

The volunteers received E25 (or placebo) as a supplement to their regular treatment for 12 weeks, and then had their inhaled or oral steroids gradually reduced, to see if E25 has a steroid sparing effect -- if it enables people with asthma to lower the amount of steroids they take without worsening of their asthma. This study has just been completed, but analysis of the results is not yet complete.

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Last Update: 5/24/06