Key Considerations in COPD When Utilizing Combination Therapy

The role of combination therapy is explored for the treatment of COPD.

Jeffrey D. Dunn, PharmD, MBA: Let’s discuss guideline-based disease management. I’m going to address this first question to Rey. I’m going to read something, and then I’ll ask you a couple of questions. Multiple studies show that combination treatment with LABAs [long-acting beta-agonists] and LAMAs [long-acting muscarinic antagonists] increase FEV1 [forced expiratory volume in 1 second] and reduces symptoms compared with monotherapy. That isn’t surprising. Generally speaking, combination therapy is more effective than monotherapy. But combination therapy may also reduce exacerbations compared with monotherapy. Additionally, the most recent GOLD [Global Initiative for Chronic Obstructive Lung Disease] guidelines support this idea of combination therapy. How do you approach the initiation of combination therapy in your practice? [Do you use it in the] first line, despite what guidelines say? Or are you still stepping up?

Reynold Panettieri, Jr, MD: I embrace the guidelines. In combination therapy, we’re using 2 drugs that have different mechanisms of action [MOAs] that are bronchodilators, meaning they increase the luminal diameter and enhance airflow. Long-acting beta-agonists activate receptors coupled with cyclic AMP [cyclic adenosine monophosphate]. The antimuscarinic agents block something that causes bronchoconstriction. Together, you’re hitting bronchoconstriction from 2 mechanisms of action.

The bottom line is 1+1=3, so you maximize bronchodilation. Bronchial airflow restriction causes symptoms, so I start by using 2 drugs in 1 inhaler out of the box. It’s simple to use. They’re daily doses. But you maximize bronchodilation following the guidelines. The next step is, when do we add inhaled steroids? We’ll come back to that, but first-line therapy is a long-acting muscarinic antagonist, LAMA, and a long-acting beta-agonist, such as formoterol or vilanterol. The 2 of them together in 1 inhaler is my first-line therapy.

Jeffrey D. Dunn, PharmD, MBA: This is relevant because over my career, looking at guidelines, it was always like 6 steps and step-up. I’m thinking more asthma. It was an ICS [inhaled corticosteroid] monotherapy, and then you moved to combination. We saw in the market that the majority of providers moved to combination therapy. It makes sense. You’re hitting 2 different MOAs, and you’re going to have a higher likelihood of success or clinical benefit, with probably fewer follow-ups. Intuitively, it makes sense. But for an alternative to that, or a different spin on that question: are there patients for whom you wouldn’t start combination therapy and you’d consider monotherapy?

Reynold Panettieri Jr, MD: Yes. In those instances, if there’s a contraindication to the use of an antimuscarinic agent, that would be the patient I’d reserve that therapy on. On occasion—at least with men with urinary hesitance—that could be exacerbated, although the antimuscarinic agents get broken down at the bronchial epithelial level. You get very little systemic absorption. However, if there’s a contraindication to the antimuscarinic agents—another one is narrow-angle glaucoma—you may want to reconsider the use of a LABA. If there’s narrow-complex tachycardia or other arrhythmias, maybe the LABA wouldn’t be the drug of choice, and you’d go with an antimuscarinic. But that’s probably less than 5% or 10% of the total population. It’s pretty uncommon.

Jeffrey D. Dunn, PharmD, MBA: Perfect. It’s the exception more than the rule.

Mike Hess, MPH, RRT, RPFT: One thing I’ll throw out there as a follow-up is that Rey is right on point, but we often see a lot of barriers to adherence to that ideal guideline-based therapy. We have people who [are affected by] the social determinants of health and some of those barriers. They may not have those medications in their pharmacy. They may have their care driven by a primary care provider instead of a pulmonologist because they don’t have access to a pulmonologist. We all know the barriers that primary care faces. It’s important to note that the guidelines are fantastic and we should be doing that, but there are a lot of folks who unfortunately don’t have access to that kind of evidence-based care.

Reynold Panettieri, Jr, MD: Mike, you’re absolutely right. In some instances, an MCO [managed care pharmacy] may approve the drug separately. When you give 2 inhalers to a patient, that doubles your likelihood of poor adherence. They will probably adhere to different medicines at different times. You need to understand with shared decision-making, can you use this drug? Do you have access to the drug? Can you afford it? If the answer is no, then the provider needs to tailor the prescription to the needs of the patient.

Jeffrey D. Dunn, PharmD, MBA: With things like inhalers, injections, and eye drops, using multiple therapies is a little different from taking 2 tablets. It isn’t the same thing when we’re talking about fixed-dose combinations and components, so that’s a great point.

Courtney Crim, MD: I’d like to add to what Mike and Rey said related to initiating therapy. I agree: for the patients we see as specialists, it’s rare that monotherapy will be appropriate by the time a patient comes to see us. There may be some patients seen by primary care doctors who have very minimal symptoms and near-normal measured lung function in whom monotherapy may be appropriate. That comes down to the individualization of therapy and which one takes that into consideration.

Jeffrey D. Dunn, PharmD, MBA: Which is important in this disease state, for sure. Perfect.

Transcript edited for clarity.

CH LogoCenter for Biosimilars Logo