Pharmacologic Treatment Options and Challenges

Peter L. Salgo, MD: I want to talk about some of the therapies that we had, traditional therapies. You went to the doctor’s office, you got some quick-relief stuff, right? You got the short-acting beta receptor agonists, the SABAs. What else did we have at that point?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Well, typically your mild asthmatics are being prescribed short-acting beta agonists, rescue medication we call it. And then when they reach persistent, and I think in all levels of our guidelines in terms of the NHLBI [National Heart, Lung, and Blood Institute], pediatrics, and adults, inhaled corticosteroids are the preferred controller medication. Although, in the very young children, I believe montelukast has equal standing. And then as you get more severe, you’ll add a long-acting beta agonist, and then there’s a number of other medications available.

Peter L. Salgo, MD: Cromolyn was in there, right?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: You can hardly get Cromolyn anymore.

Peter L. Salgo, MD: But back then, Cromolyn was a standard therapy.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: They had to take it 4 times a day to work.

Don A. Bukstein, MD: Cromolyn, it worked well in a certain phenotype. And, in fact, that phenotype kind of defined as response to sodium Cromolyn. It had to be used 4 times a day really to get good efficacy. And we had controller medications—Cromolyn, theophylline was a controller medication.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Which almost nobody used it.

Don A. Bukstein, MD: We’re going back to my era now.

Peter L. Salgo, MD: I remember theophylline.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Yeah, I got a few patients toxic in my....

Don A. Bukstein, MD: And then inhaled steroids came in, and inhaled steroids really were a boon to asthma control because then we could control instead of half the patients, we could control the vast majority of patients. And we thought if we went high enough on the doses of inhaled steroid, we would get better control. The fact was that wasn’t true at all. Once we got to medium, to higher doses, there was a plateau and going higher really didn’t get us anything. And then we figured out how to add in long-acting beta agonists, so albuterols that were extended. Still, probably the best outcome you can look at and certainly big system like Kaiser and other big systems, Mayo, look at this, is kind of how much medication someone is using, not only their adherence to controller medication like inhaled steroids or leukotriene antagonists, but how much of that albuterol or short-acting beta agonist they’re using. And most of our patients don’t give us accurate information about that, and that’s really important. But, in the future, we’re going to be able to, digitally. We’ll have all this information coming to us, so we’re going to be able to tell a little bit better who’s using too much control.

And the other thing is those bursts of oral steroids. Because oral steroids are cumulative. Over time it’s a cumulative adverse effect, whether it’s cataracts and glaucoma, whether it’s osteoporosis, whether it’s increased risk for heart disease. There are so many potential long-term adverse effects of these frequent bursts of oral steroids that it really is incumbent on us to try and figure out ways that we can minimize those long-term effects.

Peter L. Salgo, MD: How do you know when you’ve topped out on oral steroids?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: What do you mean, “topped out”?

Peter L. Salgo, MD: In other words, they’re not working any more. They’re doing more harm than good. How do you know that’s the end of the oral steroid pathway?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: When they’re in your office every week sick, calling every other night, and you are going to the hospital [emergency department] and getting hospitalized.

Don A. Bukstein, MD: Sometimes it’s really subtle though. I mean, John will tell you, I know we’ve talked about it before. Sometimes you, even I who is really concerned about the adverse effects, lose track, because so many different people in the systems are prescribing oral steroids.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Yes. That’s a very good point.

Don A. Bukstein, MD: It’s not just you. And remember, they’re also on inhaled steroids. They’re on topical steroids. They’re on intranasal steroids. These patients have a big steroid burden. And one of the unmet needs of these patients is trying to decrease this exacerbation and get rid of some of that steroid burden.

John J. Oppenheimer, MD: And treating-ly, a lot of these patients who have become steroid dependent are doing it because of nasal polyps simultaneously.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: That’s right.

John J. Oppenheimer, MD: What’s exciting are these biologics, which are in research and, so far, have shown a nice signal of efficacy in nasal polyposis. This could be a real game changer for these people.

Peter L. Salgo, MD: From a payer’s perspective, what are the big challenges here? All these medications were out there. With all of them we’re mixing and matching. Some of them work but fell out of favor because you have better medications. At the end of the day though, from a payer’s perspective, what was important?

Louis Christos, RPh: For the longest time it’s always been poor compliance. It’s always been, initially, patients’ inability to use the inhalers properly. Then it was poor adherence with these medications. It was the adverse effects of these medications, and it was also, let’s be honest, they don’t have symptoms every day, so they don’t take their medications every day, which obviously defeats the purpose of a maintenance medication.

Peter L. Salgo, MD: But they would always take their rescue meds, right? If they got sick, they would take something.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Well, the truth of the matter is a lot of my patients, even though I know my nurse spent a lot of time educating them, they come and they pull out of their purse, it’s usually a woman who has a purse, and they have the inhaled steroid. And they say, “All right, it’s not working or relieving. And then the other medication…” they get confused about the purposes of their medication.

Peter L. Salgo, MD: There was a famous episode of House, M.D., in which a patient said her inhaler wasn’t working and she sprayed it behind her ears.

John J. Oppenheimer, MD: But as a payer it’s interesting, and you pointed this out. If you look at the data, what’s the average number of inhaled steroids that people actually fill a year? If they should fill 12, it’s 3. For combination therapy where they’re even getting a positive reinforcement it is 4. It is 4.12 to be exact.

Louis Christos, RPh: It’s not that much.

John J. Oppenheimer, MD: So it’s not high. But what’s really scary, as Peter mentioned, is what do they do when they’re having an exacerbation? There’s one study that shows that people dial up their short-acting beta agonist, but what do you think they do with their inhaled steroid? Actually diminish it. So that’s really scary.

Don A. Bukstein, MD: And the reason is if someone who has asthma, when you’re taking your inhaled steroid, you don’t get positive reinforcement.

John J. Oppenheimer, MD: Correct.

Don A. Bukstein, MD: And, in fact, when you get a cold or a virus, it actually burns a little bit. So you get kind of a negative reinforcement. Adherence though isn’t as easy as, “Ooh, I’ve forgotten my medication.” Or, “I mixed up my medication,” isn’t as easy as, “Oh, I’m not taking it correctly.” It’s usually not, “Oops, I forgot to take my medicine,” or, “I’m not paying attention to taking it correctly.” It’s, “I’m not going to take it. I don’t need to take it,” and a lot of other reasons. Adherence is not a simple matter of just reminding people to take their medication.

Louis Christos, RPh: But it’s no different than any other chronic disease.

Don A. Bukstein, MD: But it’s much worse. If you look at adherence patterns of all the chronic diseases, asthma with inhalers is the absolute worst.