Combination Therapy for COPD

Preferences for combination regimens for the treatment of chronic obstructive pulmonary disease and important considerations when selecting an appropriate regimen.

Transcript

Neil B. Minkoff, MD: You guys have covered the whole waterfront, and there are like 1000 follow-up questions I want to ask. Let me just narrow it down to a few of the important ones. One of the things I’ve been trained to do, when we start talking about the benefits of combination therapy, my job is to say, “What are the risks of it? Are there significant risks, and do we need to be concerned about it?” Then I want to come back to you in terms of working your way up to combination therapy and how you manage against the guidelines. But let’s start with the risks and then see if those are impacting these decisions.

Frank C. Sciurba, MD, FCCP: The 1 risk that I take into account lends to asking why even worry to add the ICS [inhaled corticosteroid] on to the double? Because it might help or it might not help. But the fact is that 2% to 3% of patients per year on ICS therapy can get pneumonia. If you’re eliminating 25% of the flare-ups, if you pick the right patient, that may be a risk that the system and the patient is willing to accept. But there is that risk of immune suppression and a minor infection spreading into a pneumonia.

With the long-acting bronchodilators, I’m with Byron. There’s a lot of theoretical literature. Certainly, we know there’s a small signal with regard to cardiovascular disease and sudden death. But I always say that in a baseball stadium, you pick out 3 people in a year and they may not do well. The rest of them feel better. Is that a choice you’re willing to make? Actually, the biggest problem I see with the LAMAs [long-acting muscarinic antagonists] in men who have borderline urinary retention with prostate problems is that we can tip them over. So I’m careful in that situation. Those people weren’t included in the clinical trials, by the way, but they come to my clinic. So I am a little cautious sometimes with the anticholinergics. But in general, the LAMAs and LABAs [long-acting beta-agonists] are extremely well tolerated.

Byron Thomashow, MD: I agree with that 100%.

Neil B. Minkoff, MD: Any differences?

Byron Thomashow, MD: No. The only thing I would add is that while the pneumonia concern is the greater concern that I have, ICS has been potentially associated with some cataracts and eye-related issues. There’s a potential issue with your bones if you’re using high enough doses. Like any other medicine, you have to balance the risks and benefits of everything that you’re going to use. In general, the medicines we have available in COPD [chronic obstructive pulmonary disorder] are very well tolerated and reasonably effective in what we’re trying to do. That doesn’t mean we don’t need better. We do. We need to define therapies for specific types of disease, but it’s helpful.

I will come back to an issue that we haven’t discussed, and I’d be interested in Frank’s take. We talk a lot about advancing therapy. Going from LAMA/LABA to triple, there are some situations where you might go to triple faster. But if you have someone, for example, Frank, who isn’t a frequent exacerbator, who comes to you and who had gotten stuck on triple therapy, recognizing that we both have some concerns about that, there are potential arguments and there are studies that have suggested that you might be able to cut back on the dose. That’s 1 of those areas in which maybe that eosinophil count that you talked about before might help you a little, isn’t that right?

Frank C. Sciurba, MD, FCCP: Yes. I’m a believer in looking at the CBCs [complete blood counts] that are over their chart. Often, they’re gathered during exacerbations, but you’re describing patients who don’t exacerbate. But it’s a rare patient who, at some point, didn’t get a CBC. If you look at the eosinophil count, that little count that we just kind of ignore—it doesn’t mean a whole lot, and it has something to do with parasites, maybe asthma—if it’s under 100, then they’re probably not going to benefit a whole lot from inhaled corticosteroids.

Certainly, I would never put anybody who has no history of exacerbations and 100 or fewer eosinophils on an inhaled corticosteroid. And the counter to that, if somebody comes in without a flare-up history, I’m probably going to convert them to a LAMA/LABA if they’re symptomatic and dyspneic.

Neil B. Minkoff, MD: Do you guys prefer the fixed-dose combinations, or do you prefer to ramp up with 2 different inhalers?

Byron Thomashow, MD: You never want to give people 2 different inhalers if you can avoid it. It’s hard enough to get people to learn how to use 1 inhaler. I actually think that’s an area that we need to talk to Maria [Lopes] about, because it’s increasingly an issue.

Neil B. Minkoff, MD: It’s on the page here.

Byron Thomashow, MD: What happens is, you train your patients on how to use it. One of the advantages of the mobile app that the COPD Foundation has come up with is that we have all the inhaler videos available for people to look at. But you teach someone, they know how to use an inhaler, and 2 months after you’ve seen them, their insurance company has changed the formulary and they’ve switched them to a new drug that has a different device. If you don’t know how to use the device, you’re wasting your time.