FDA Advisers Urge Curbs On Some Asthma Drugs

Advisers to the Food and Drug Administration have recommend that drugs Serevent and Foradil no longer be used for asthma. Top-selling Advair was not affected by the recommendation.

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MICHELE NORRIS, host:

There is news today for people who take asthma drugs. An advisory committee to the Food and Drug Administration gave mixed reviews to a popular class of those drugs. The committee says that two of the four drugs should not be used to treat asthma. Two others, the committee says, are OK to use. NPR's Joanne Silberner is here to explain this, and, Joanne, let's start with the drugs themselves. Which drugs are we talking about?

JOANNE SILBERNER: There are four drugs. They are known as long-acting-beta-agonists, and they are called Serevent, Foradil, Symbicort, and Advair. They're meant only for serious cases when other drugs just aren't enough, but they are very widely used. Advair is the most popular one, and that's used by four million people.

NORRIS: So, why do the committee say that two of the drugs are OK and that two aren't?

SILBERNER: Well, they work in different ways. The first two drugs, Serevent and Foradil, they act - they just do one thing. They relax the muscles around the airways and the lungs, and that's one of things that happens during asthma - those muscles seize up. The other two drugs, Advair and Symbicort, they have a second drug in them that does a second thing. It reduces inflammation, which is also bad in an asthma attack.

Now, a number of studies show that when you use the two drugs at once, it's much better, so if you are using one of the single drugs, then the suggestion is you had a second drug that does that second thing of reducing inflammation. And a lot of people on the committee thought, you know, what let's - its better for people to take it on one than, you know, that they get that second drug.

NORRIS: A lot of questions have been raised in the course of this process. What are the real issues here?

SILBERNER: Whether they cause more asthma exacerbations and hospitalizations and deaths. There were some studies of the single-acting drugs that suggested that there could be more hospitalizations and deaths with them. And, of course, that is not something that you want in a drug that you are using to treat asthma.

Studies of the other two drugs are pretty clear that they are beneficial, and, you know, one of the issues was those first two drugs being used alone. The (unintelligible) anecdotes to people dying holding those drugs in their hands because they were thinking that they were fast-acting drugs. They were not, actually. They're long-acting drugs that need to be taken daily.

NORRIS: It sounds like it's really hard to figure out whether these drugs are helpful or harmful. Why is it so complicated?

SILBERNER: Because asthma is a really complicated disease. What you really need to do to do a clean study that's clear is to have a lot of people with the disease. And from person to person, asthma can vary. Within one person, it can get worse; it can get better.

And then what you do is, you take this clean group of people and give half of them one drug and see how it works. People with asthma are often on other drugs, or they may not be on other drugs when they should be on other drugs. It's hard to tell what they are taking. Sometimes they don't take daily medicine because they are feeling fine, so it gets very messy.

And the numbers are low. The numbers of problems are low, which makes statistics very difficult, and one study, for example, that did show deaths in the group was 13 deaths among 13,000 people. It's a pretty low number.

Another issue is, how we do drug studies in this country, that, for most part, they are done by the drug companies, and a lot of people would like to see them done by the government or someone else, so that the results are very clear and that the studies are done comparatively.

NORRIS: The two drugs that were approved today, is this going to mark the end of all the safety questions attached to these drugs?

SILBERNER: No, the committee's asking for more research. They were especially worried that a lot of research hadn't been done on kids. It used to be that research was always on adults. They have just started recently in the last few years looking at kids, and a lot of kids have asthma. So it's especially important to get those studies done.

NORRIS: That's NPR's Joanne Silberner. Joanne, thanks so much.

SILBERNER: Thank you.

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FDA Advisory Panel Weighs In On Asthma Drugs

An advisory committee to the Food and Drug Administration says one type of a long-acting asthma medication has more benefits than risks, but another type has more risks than benefits. The decision may help doctors and patients figure out the best path to take when deciding on asthma medications.

The medication under review is a long-acting beta agonist, or LABA. It comes alone, as Serevent (salmeterol) and Foradil (formoterol). Two other LABAs — Advair (salmeterol plus fluticasone) and Symbicort (formoterol plus budesonide) — contain a second drug that reduces inflammation in the lungs.

The drugs are meant only for people with serious asthma, where other drugs have failed. And unlike "rescue" drugs, long-acting beta agonists won't help with an acute attack of asthma. They are meant to be taken daily.

The committee considered clinical trials on tens of thousands of people. Several studies of the single-action long-acting beta agonists showed they might actually increase the risk of asthma-related hospitalizations and deaths. So the advisory committee gave its stamp of approval only to the double-action drugs. It also asked for more research, especially in children and adolescents.

Questions about the drugs' safety were sparked by a study several years ago showing that salmeterol (Serevent) could worsen asthma, and in rare cases even cause death.

The FDA put a warning on salmeterol and, later, the labels of other long-acting beta agonists, but it didn't pull the drugs off the market. Doctors and patients were left to decide on their own. Lung specialist Gregory Diette of Johns Hopkins University began a practice of telling his patients about the study.

"I try to give them some idea of what the magnitude of the risk is. In that study, there were three people out of 13,000 who had an asthma-related death in the placebo group, and 13 out of 13,000 in the active treatment group, and so it was about an extra 10 people per 10,000," he said.

Most of his patients who were taking the drug at the time quit taking it. Now, with new patients, most opt to take it.

"For some people the risk is too great, and for some, it's not very much at all, and it's a very personal decision," Diette said.

There is already a warning on the drugs — not just salmeterol but also salmeterol/fluticasone (Advair), formoterol (Foradil) and formoterol/budesonide (Symbicort).

Most lung specialists say LABAs have made life better for their patients — previous medications for people with serious asthma had a lot of uncomfortable side effects. The few outright critics say those doctors are just saying that because the drug companies pay them to speak or to do research. Most asthma experts, in fact — including all of the ones in this story — have taken money from pharmaceutical companies, which finance most of the research on these drugs.

The asthma doctors' professional organization and the American Academy of Pediatrics support the use of long-acting beta agonists. The National Institutes of Health issued guidelines last year saying that the drugs are worth the risk, so long as the drugs are used correctly — only in children and adults with serious asthma, and only in conjunction with inhaled steroids.

"You get greater improvement in lung function; you get less asthma attacks and less need for rescue medications," William Busse, one of the authors of the NIH guidelines, said about the long-acting beta agonists.

He bases that on multiple studies that show an overall benefit. But four FDA staffers have done a new analysis combining many studies. They conclude that the drugs are too risky for use in children younger than 18. On adult usage, they say two of the four drugs should not be used for asthma, though the group splits on the other two drugs in the class.

One thing everyone agrees on: The various studies of the drugs all have problems. Some studies are too small. In some, researchers didn't collect information on how sick the patients were to begin with, or what other drugs they were taking.

And whenever scientists evaluate a lot of insufficient studies, there are a lot of different opinions. Busse said he thinks the analyses that say the drugs do more good than harm are right.

"If these medications were really unsafe, epidemiologically we would have seen a change in asthma morbidity and asthma hospitalization, and we're not seeing this at the present time," Busse said.

But he's glad the FDA is airing the issue. So is Stephen Teach of Children's National Medical Center in Washington, D.C., who runs an asthma program for inner-city children. Teach doesn't want to see a complete ban on the long-acting drugs.

"My overarching concern is that banning completely would force doctors and patients to rely on other drugs, which may be less effective and potentially even less safe," Teach said.

The agency usually follows the advice of its committees — which in this case would mean either beefing up the warnings on Serevent and Foradil — or recommending that those drugs not be used for asthma.

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