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New Drug May Reduce Use Of Corticosteroids For Asthma

A twofold drop in the frequency of allergic asthma attacks, a reduction in their severity and a reduced need for corticosteroid treatment are the promising results with omalizumab, according to an international study.

The study was performed by scientists in Switzerland, the USA, Germany, South Africa and the United Kingdom and was published today in the European Respiratory Journal (ERJ).

Allergic asthma is the cause of about 75% of adult asthma cases.

The results are from a multicenter, randomized, double-blind trial involving more than 500 allergic asthmatics.

The cornerstone of this success is omalizumab, a new drug that opens the way for an immunotherapeutic approach to allergic asthma treatment. For this drug, a recombinant monoclonal antibody is intended to block immunoglobulin E (IgE), which plays a key role in the allergic reaction.

The multicenter international study involved 274 patients receiving omalizumab and 272 others who received a placebo. It very clearly demonstrated the potential benefits of the new treatment.

Professor Markus Soler of Basel, Switzerland, the main author of the ERJ article, states that "the number of asthma attacks (exacerbations) suffered by the omalizumab patient group was reduced by 58%: while 30.5% of the patients in the placebo group presented at least one attack during the seven months of the study, the figure was only 12.8% in the omalizumab group, a very significant difference".

These results were obtained in good tolerance conditions and the incidence of secondary effects was the same in both treatment groups.

Moreover, the ERJ study also shows that the considerable therapeutic benefit is retained even when the corticosteroid dose is progressively reduced.

This additional advantage is emphasized by Pascal Chanez, of Montpellier (France) in the editorial accompanying the ERJ article: "The difference remained the same, despite the inhaled corticosteroid (ICS) reduction strategy used. Despite this step-down in ICS dose, there was a significant reduction of symptoms and rescue medication use and a small increase in airway function in the omalizumab group."

It is known that the antibodies playing the key role in allergic reaction are the E immunoglobins (IgE). Their role is to recognize antigens and to launch the reaction of the effector cells to which they are attached, essentially mastocytes, which release inflammatory substances responsible for bronchial muscular spasms.

IgEs have two ways of connecting: either by capturing antigens or by attaching to effector cells. The IgE connection site is specifically recognized by omalizumab: a molecule of IgE produced by an allergic patient can therefore as easily be fixed to the surface of an effector cell as to an anti-IgE antibody. In both cases, it is capable of fixing specific antigens, but binding with omalizumab prevents the chain of events leading to inflammation.

"The principle of omalizumab treatment involves preventing new IgE molecules reaching tissue mastocytes by fixing newly synthesized IgE molecules," explains Markus Soler. "Consequently, the quantity of IgE-carrying tissue mastocytes will decrease progressively and they will be replaced by new mastocytes without IgE in need of binding.

"However, the process takes six to 12 weeks, so an immediate effect should not be expected. This also explains the various phases that had to be included in our study protocol."

As the article's nine authors explain in ERJ, the study began with an initiation period of four to six weeks, during which all patients were treated with the same inhaled corticosteroid (beclomethasone) in a dose equivalent to that which had previously controlled their asthma.

Subsequently, over a seven-month period, the two groups received, on a fortnightly or monthly basis, injections of omalizumab adjusted to their body weight, or a placebo.

Over the first 16 weeks, the initial corticosteroid dose was maintained at a constant level. This phase corresponded to the progressive disappearance of IgE-covered reactor cells in patients receiving the drug.

The second 12-week period was also put to good use: a successful attempt was made to reduce the corticosteroid dose without compromising asthma control.

The results suggest that the drug's benefits may be accessible to patients beyond those involved in the study.

Soler comments:

"I think that, initially, omalizumab will be used to treat patients with moderate to severe asthma, quite similar to those involved in our study, who suffer symptoms or attacks under conventional treatment.

"But the patient group that can gain the greatest benefit from omalizumab is so far not very well defined: patients who suffer from slight asthma could have a purely allergic condition and gain greater benefit from omalizumab treatment.

"Since this treatment is applied by the doctor, it could also be used on patients who are not sufficiently compliant.

"It should be added that omalizumab also treats the entire set of allergic symptoms, including those affecting the nose, eye and even, possibly, the skin, unlike even the most powerful inhaled corticosteroids.

"Practically all experimenters have already observed such results in certain of their patients," confirms Markus Soler.

Admittedly, there are still a number of obstacles to the widespread use of omalizumab.

The drug's price is relatively high and there is still no comparative study demonstrating that this costly treatment should be generalized. Moreover, since the treatment is relatively new, with data available for only one year, it will certainly be some time before it can be regarded as truly safe.

"In the long term," Markus Soler explains, "there may be unexpected effects, such as adverse reactions that are as yet poorly known. We must certainly pay particular attention to such effects in children, for preventing IgEs from playing their role could have either positive or negative effects for immune system development."

[Contact: Dr. Markus Soler]

02-Aug-2001

 

 

 

 

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