Panel Votes Against Two Drugs for Asthma

By GARDINER HARRIS

ROCKVILLE, Md., 12 dec 2008 — A panel of federal drug experts recommended on Thursday that the drugs Serevent and Foradil be banned from use in the treatment of asthma, but the experts said that Advair and Symbicort, which are far more popular, should continue to be used.

The experts, gathered by the Food and Drug Administration, said that too many doctors used Serevent and Foradil inappropriately, and that asthmatic patients were often fooled by their own symptoms and used them incorrectly. For children, the experts voted unanimously to ban the use of Serevent and Foradil. For adults, the panel voted 17 to 10 to ban Serevent and 18 to 9 to ban Foradil.

Serevent and Foradil widen lung airways but increase the risks of death unless they are paired with a steroid. The two drugs’ labels already warn doctors to pair them with steroids, but half of patients do not get a steroid. And even when patients get a steroid, many fail to take it.

GlaxoSmithKline, the maker of Serevent, and Novartis, the maker of Foradil, argued that doctors wanted the freedom to mix and match these kinds of drugs with steroids as they wish. But Dr. Jesse Joad, a panel member and a pediatrician from University of California Davis Medical Center, said she did not “want to give a drug that is making the disease you’re treating worse.”

Both Serevent and Foradil are also approved to treat chronic obstructive pulmonary disorders like emphysema, so even if the F.D.A. follows the panel’s advice, the drugs will remain on the market.

Asthma is caused when airways within the lungs spasm and swell, restricting the supply of oxygen. The two primary treatments are steroids, which reduce swelling, and beta agonists, which treat spasms. Rescue inhalers usually contain albuterol, a short-acting beta agonist.

Serevent and Foradil are longer-acting beta agonists intended to prevent attacks. Used without a steroid, however, these drugs have been shown to increase the risks of more severe attacks. Advair and Symbicort pair these longer-acting beta agonists with steroids.

The panel voted unanimously that Advair should continue to be used in asthmatic adults and supported its use in adolescents by 23 to 3 and in children by 13 to 11. The panel also voted unanimously to support Symbicort’s use in asthmatic adults and 20 to 5 to support its use in adolescents. Symbicort is not approved for use in children.

Earlier, some top F.D.A. safety experts recommended that all four drugs should be banned from treating asthma in both adults and children, while other F.D.A. experts said the drugs’ benefits outweighed their risks. The agency has struggled for years to balance the risks and benefits of the medications, and this week’s advisory committee was the fifth to tackle the medicines.

Like other drug-safety controversies, the debate largely pits those who see the controversy through the eyes of a single patient against those who study populations. Since the drugs may lead to one death in somewhere between 700 and 4,000 patients, few doctors have had a patient who died from using the drugs. So most doctors focus on the benefits of the drugs, which allow many of their patients to play sports, go to work or lead normal lives.

Among the supporters of the drugs was Anne Dorsey of Baltimore, who described the night that her 13-year-old son, Julian, nearly died from an asthma attack. Julian spends much of his life in the hospital and is now taking Advair.

“I have to ask you not to let him perish” by banning the drugs, Ms. Dorsey said. Then Julian stepped to the microphone. In a reedy voice, he said that Advair had cut in half the time he spends in the hospital. “Life got a lot easier,” he said, “and without Advair, I don’t know what I’d do.”

The American Academy of Pediatrics, the American Academy of Allergy Asthma and Immunology and the American College of Allergy Asthma and Immunology all support the continued use of the medicines.

The F.D.A. experts who recommended that the drugs no longer be used in asthma tend to view such issues on a population basis. With more than three million asthmatics in the country taking the medicines, the drugs’ risks could cause thousands of deaths each year.

For these experts, long-acting beta agonists — while they may make patients feel mildly better — have few concrete benefits that would justify so many deaths. And sudden death is a risk that, even when patients are warned about it, is not something they can control by behaving differently.

Asthma is a highly unpredictable disease that can lull patients into complacency, and the effects of the medicines can worsen this problem. Severe, life-threatening attacks can strike out of the blue, and milder symptoms may not predict more severe ones.

The beta agonists — by relaxing bronchial spasms — treat mild symptoms and make patients feel better immediately. Feeling better, these patients — if they are taking beta agonists and steroids separately — may decide against taking the steroids since steroids have few immediate benefits. Patients who are prescribed both drugs separately get fewer refills of the steroid than of the beta agonists. Such patients leave themselves vulnerable to severe attacks and death.

Dr. Sean P. Hennessy, a panel member from the University of Pennsylvania, said that the F.D.A. should withdraw its approval of Serevent and Foradil in the treatment of asthma to prevent patients from taking these medicines without steroids. And he called for Glaxo to begin a large safety study of Advair.

“Given the problems and the nearly $8 billion in revenue earned from Advair, this seems imminently plausible,” Dr. Hennessy said.

Dr. Fernando Martinez, director of the Arizona Respiratory Center at the University of Arizona, noted that far too many patients whose conditions could be treated adequately with steroids alone were instead receiving Advair or Symbicort, which are riskier and more expensive. He said the drugs’ makers must educate doctors better, but he said “it would be irresponsible to withdraw these medicines” because they improve patients’ lives.

Doctors face difficult choices with children whose asthma remains uncontrolled with low-dose steroid treatment. If they increase the steroid dose, the risks include stunted growth, acne, greater vulnerability to infections and affects to skin, eyes and bone. If they add a long-acting beta agonist, the risks of death, although still small, increase