ACAAI: When Inhaled Corticosteroids Fail, What Then?

PHILADELPHIA, Nov. 15 -- When inhaled corticosteroids don't adequately control a patient's asthma, the choice of next-best add-on therapy is open to debate.

So specialists did just that at a symposium, sponsored by GlaxoSmithKline, held in conjunction with the American College of Allergy, Asthma & Immunology. Each argued for one possible add-on therapy--long-acting beta agonists, immunotherapy, leukotriene receptor antagonists, and plain old aspirin.

Long-Acting Beta Agonists (LABAs)

LABAs enhance the anti-inflammatory action of corticosteroids, said Harold Nelson, M.D., of the National Jewish Medical and Research Center in Denver. When combined with corticosteroids, they have proved effective at improving lung function, reducing symptoms, and preventing exacerbations in patients with poorly controlled asthma.

For example, a pooled analysis of 12 studies that included 4,576 patients found that those who merely received a higher dose of inhaled corticosteroids were 35% more likely to have exacerbations than those who received a combination of inhaled corticosteroids and the LABA Serevent (salmeterol), Dr. Nelson said. The study was published last year in Thorax.

"While serious adverse events have been associated with monotherapy, there is no evidence that there is any safety concern when used in conjunction with inhaled corticosteroids," he said.

Immunotherapy

Immunotherapy is the only approach that actually alters patients' disease state, shifting their abnormal TH2 immune response to the more normal TH1 response, said Ira Finegold, M.D., of St. Luke's-Roosevelt Hospital in New York.

All other therapies "are just Band-Aids," Dr. Finegold said.

To support the efficacy of immunotherapy, Dr. Finegold cited a Cochrane Database analysis published in 2003. The analysis included 75 trials involving 3,506 patients. Patients underwent immunotherapy for a variety of allergens, including dust mites, pollen, and animal dander.

Overall, immunotherapy significantly reduced allergen-specific bronchial hyper-reactivity, Dr. Finegold said. There was no consistent effect on lung function among the trials, but this may have been because of the different methods used to measure lung function, he said.

"Complete long-term asthma control does not occur with pharmacotherapy," Dr. Finegold said. "It is important to recognize that treating the allergic component with immunotherapy may be the solution."

Leukotriene Receptor Antagonists (LTRAs)

The chief advantage of LTRAs is that they come in once-daily pill form, so compliance is good, said Donal Cockcroft, M.D., of the University of Saskatchewan in Saskatoon.

In fact, a once-daily tablet has about twice the adherence of inhaled corticosteroids. "This may allow the LTRA with as lower degree of efficacy to have a greater effectiveness in the real world," Dr. Cockcroft said.

In general, LTRAs are not as effective as inhaled corticosteroids in controlling symptoms, he said. Nevertheless, LTRAs may be appropriate for the "vast majority" of asthmatics with mild asthma." For these patients, LTRAs are sufficient to manage the disease without the risk of side effects associated with inhaled corticosteroids, most notably slowed growth in children, Dr. Cockcroft said.

Aspirin

A pilot study of 20 patients with asthma and rhinitis suggests that aspirin may adequately control asthma in some patients, said David Lang, M.D., of the Cleveland Clinic.

The patients took aspirin (650 mg twice daily) for up to five years. They experienced improvement in olfaction, reduced rate of need for sinus surgery, and reduced emergency department visits for asthma, Dr. Lang said.

"This study, although uncontrolled, implies that the therapeutic utility of aspirin in aspirin-tolerant asthmatics merits further study," he said.

Dr. Lang also noted aspirin's well-documented ability to reduce the risk for cardiovascular disease, and he said that aspirin therapy would be especially beneficial for asthmatics with cardiovascular co-morbidity.

"It is important to note that aspirin should still be viewed as the wonder drug that still works wonders," he said.

At the conclusion of the debate, the audience was invited to choose a winner by applauding. Dr. Nelson, the advocate for LABAs, garnered the most audience applause and was designated the winner.

The symposium was sponsored by GlaxoSmithKline.