COPD Triple Therapy: Appropriate Patient Population

Key opinion leaders highlight the triple therapy approach from the most recent GOLD guidelines, including ICS, long-acting beta-agonist (LABA), and long-acting muscarinic antagonist (LAMA).

Jeffrey D. Dunn, PharmD, MBA: Which patients with COPD [chronic obstructive pulmonary disease] are appropriate candidates for triplet therapy? Rey, I’ll ask you to start if you don’t mind.

Reynold Panettieri Jr., MD: Courtney rang the bell there several times. No. 1, ICS is an inhaled corticosteroid. I consider an ICS when I haven’t met the therapeutic goals—maybe dyspnea, but [also when there are] exacerbations. The moment a patient has an exacerbation, that puts the patient in a different light. That’s a patient for whom I’d consider an ICS. If they haven’t exacerbated, then I’m more a LAMA [long-acting muscarinic antagonist]–LABA [long-acting beta-agonist] guy. Once you exacerbate, exacerbations aren’t tolerated. They put people at risk—especially if it’s a hospitalization or ED [emergency department] admission—and that’s when I’m going to add an ICS to LAMA-LABA. I feel very strongly about that.

Courtney also touched on biomarkers. What biomarker could predict therapeutic response to an inhaled steroid? The most recent data—we’re talking about the last 5 years only—if the serum eosinophils are elevated greater than 150 cells per μL or, more important, greater than 300 cells per μL, that puts the patient in [the category of] most likely to respond to an ICS. Is it uniform? No, but it gives us an indication that this patient is driven by inflammation, and that might be the ideal patient. [I’d go with] LAMA-LABA to start out. If they exacerbate, then I’m adding an ICS. I’m predicting therapeutic response with the serum eosinophil count, but I’m also going to follow with FEV1 [forced expiratory volume in 1 second] on a routine basis.

Mike Hess, MPH, RRT, RPFT: I suspect that’s where we’re going to start seeing a lot of the evidence-based practice go. It probably isn’t going to be triplet therapy right off the bat for most people. There are going to be those for whom it’s individualized. Maybe you already have an eosinophil count when you’re starting therapy. But as Rey said, once you’re not meeting your goals, GOLD [Global Initiative for Chronic Obstructive Lung Disease] has this concept of treatable traits. You’re either treating dyspnea, symptom burden, or exacerbations. If you aren’t meeting those goals, you’re going to continue along those pathways, and adding an inhaled corticosteroid is a well-accepted treatment for reducing the exacerbations on that treatable-trait pathway.

Reynold Panettieri Jr., MD: I want to highlight in bold—Courtney and Mike mentioned this—that there’s a risk-benefit ratio. Typically we think topical steroids are no real problem. That’s wrong in COPD. In the most severe patients, pneumonias occur. Typically, the pneumonia causes only morbidity, not mortality. That’s the good news. It’s interesting. The formulation may be different between drugs like fluticasone and budesonide, although it hasn’t been systematically studied as well as we want. Keep that in mind.

Courtney Crim, MD: I’ll add on to what has been said by Rey and Mike as it relates to inhaled corticosteroids. One goal I mentioned early on in terms of managing COPD is to reduce risk. Part of that is having an impact on disease progression. We know from a couple of studies that an ICS in combination with a long-acting beta-agonist can have an impact on the rate of decline in FEV1. Patients don’t come to a physician complaining that their FEV1 is declining at an accelerated rate. They come in because of symptoms or exacerbations.

Rey described how to make that decision between dual bronchodilators vs adding an ICS for triplet therapy, and what Mike said is pretty much spot on. When it comes to that individualization of therapy, and when you’re having conversations with patients based on where they are when they present to you, you still have to address what they’re complaining about, what’s impacting their life in terms of symptoms and exacerbations. Then there may be circumstances with that shared decision-making when you may mention some of these other things as it relates to one treatment vs another.

Mike Hess, MPH, RRT, RPFT: That’s a great point. It’s also important to not necessarily get caught on dyspnea vs exacerbations. When I was working in primary care, we had people who weren’t exacerbators, but we added inhaled steroids and their cough went down, and their quality of life went up a lot. Your point of adjusting therapy to reach the individual targets and goals and shared decision-making is spot on.

Jeffrey D. Dunn, PharmD, MBA: I love the comments around shared decision-making because I’ve been doing this for a long time, I’ve been involved in medication therapy management and care management, and patient engagement is so important. Their education on what they’re doing and goals are super important because we can’t tell somebody what to do. They need to be part of that process, or compliance is going to be an issue, which is going to impact outcomes and everything else.

Transcript edited for clarity.

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