On the horizon - new treatment for allergic disease

The human immunoglobulin antibody group IgE (see Diagnosis article) is responsible for many of the unpleasant and sometimes even life-threatening symptoms of allergic disease. The excessive swelling that results from a hypersensitive reaction in the lungs is what causes asthma and the allergic response to Aspergillus when inhaled as spores or when growing within the lungs as Allergic Bronchopulmonary Aspergillosis (ABPA). It is this swelling and inflammation that often has to be controlled using corticosteroids, either taken by inhaler or in tablet form.
Long term use of steroids unfortunately has a wide range of adverse side effects which people who are forced to take steroids are all too aware of (see Treatment article). Efforts are currently made to manage the dose of steroid to keep it as low as possible without losing control over the inflammation.

Recent research has shown that for ABPA sufferers taking Sporanox (itraconazole) can help to reduce the amount of steroid they must take to control their disease (see under ABPA in the treatment section of the main Aspergillus website).

An alternative approach to treating these diseases has started to come to fruition (The New England Journal of Medicine, December 23rd 1999). This approach takes the rather obvious step of attempting to eliminate the molecule which is causing the problem - IgE.
Antibodies have been made which specifically attack IgE and thus reduce the inflammation. This was not easy to do because if the body recognises these antibodies as foreign they are rapidly eliminated by our immune system. The answer was to make the anti-IgE antibody (called rhumAb-E25) as human as possible so that it would evade recognition!

rhumAb-E25 attaches to IgE and prevents it triggering the hypersensitive reaction. It also prevents more IgE being produced, reducing the potential for inflammation still further.

It was first tried on patients with mild asthma, both in inhaler form and by injection. There were encouraging results, but only for the injected drug - inhalation did not work. Unexpectedly rhumAb-E25 gave a long term anti-inflammatory effect.

Now the drug was tried by a single injection every two weeks on moderate to severe asthmatics. Again results were good with significant reduction in the symptoms of asthma in the initial 12 weeks of the experiment while steroid dosage was maintained. Over the next 8 weeks the steroid dosage was reduced systematically and there was clear indication that those taking rhumAb-E25 were able to tolerate lower doses of steroid than the placebo group. Twice as many people taking the drug were able to stop taking oral corticosteroids altogether compared with those taking the placebo.

No significant adverse side-effects have yet been recorded for this drug (and several hundred people have taken it in the trials so far) apart from an urticarial rash (nettle rash) in a few people. There is no observable toxic effect associated with clearing the drug out of the body (i.e. in the kidneys or liver).
An expected side effect was that as this drug counteracts part of the immune system (albeit an over-reacting part) it may cause a reduction in the ability of the immune system to fight off certain infections - infections where IgE normally is involved in dealing with (e.g. some parasitic infections). Experiments in mice have shown that this does not happen.

It is expected that this drug will be useful for most types of allergic disease e.g. hay fever, allergic dermatitis and allergies to inhaled dust, mould spores etc. Tests have already been carried out on hay fever with good success.

• The first is that it will be a quite expensive drug. This is offset for asthmatics by the fact that more than half the health care spend on asthma is spent on the most severe 5 per cent of the cases - the very group who stand to be most helped by this drug.
• The second is that it has to be injected. This is a problem as it requires skilled (and expensive) medical intervention every two weeks.