Combination of drugs found most effective asthma treatment

Inhalers such as Serevent Diskus and Foradil Aerolizer, which contain only a long-acting beta agonist, are not good choices for treating asthma. The reason: The chance they will be used without an inhaled corticosteroid is too great, according to three Food and Drug Administration advisory committees that gathered in December 2008. The benefits of inhalers that deliver both types of medicines -- Advair Diskus and Symbicort -- are worth the risks.

"The single agent, long-acting beta agonists should no longer be approved for use in the treatment of asthma. The combination dispensers should continue to be approved for all age groups," said Marsha Rappley, MD, chair of the FDA's Pediatric Advisory Committee and dean of the College of Human Medicine at Michigan State University. Members of the Pulmonary-Allergy Drugs as well as the Drug Safety and Risk Management advisory committees were also in attendance.

The agency is not required to follow its advisory panels' recommendations but generally does.

This is the latest in the checkered history of long-acting beta agonists. Several studies showed that these medications increase the risk of severe exacerbations. Because they seem to reduce symptoms without addressing inflammation, treatment guidelines urge that they be used only with inhaled corticosteroids, which appear to mediate their negative effects. The beta agonists also are not recommended for patients able to control their illnesses on other medications. Prior FDA advisory committee deliberations have led to the drugs remaining on the market, but with stronger warnings about possible adverse events.

Most asthma specialists received news of the latest action with trepidation. On one hand, the combination products are far more commonly prescribed than the inhalers with only a long-acting beta agonist. Also, even if the single products lose an indication for asthma, they are still expected to be labeled for chronic obstructive pulmonary disease -- so they could still be used off-label for asthma patients.

On the other hand, physicians worried about losing the single-drug products as an option or the possibility that all products containing a long-acting beta agonist drug would be pulled from the market. Many physicians view these drugs as very valuable.

"I think their conclusions were conservative and consistent with trying to optimize the safety and the use of these medications. I can see their rationale. But I'm a bit concerned that they're overcautious about the safety signal," said Stanley Szefler, MD, head of pediatric clinical pharmacology at National Jewish Health in Denver. He was speaking personally, although he testified at the joint advisory committee meeting on behalf of the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma & Immunology.

Concern also stemmed from the idea that this move might limit patient access and affect the cost of treating asthma. These drugs in two inhalers are less expensive than are the combined products.

"From a clinical standpoint, it's nice to have more options. And, from a patient standpoint, I'm concerned about cost. These medications are fairly expensive," said Richard Gower, MD, president of ACAAI. "We live in an imperfect world. All drugs have potential benefits and side effects."

Manufacturers cheered the conclusion that the benefits of combination products outweighed the risks but disagreed with the conclusion that those with only a long-acting beta agonist should no longer be used for asthma.

Statements issued by these companies said these products provided more dosing flexibility and were safe when used as directed.

"We welcome the committee's endorsement of Advair as a safe and effective treatment for asthma. ... Serevent, when used with an [inhaled corticosteroid], is an important treatment option for some patients as outlined in national guidelines," said Ellen Strahlman, MD, chief medical officer for GlaxoSmithKline.

The advisory panels also called for more studies to determine the safety of the combination products in children.