Dr Antonio Anzueto on the Benefits of Triple Therapy, Importance of Accurate COPD Diagnoses

Each year the Global Initiative for Chronic Obstructive Lung Disease (GOLD) releases a report on updated guidelines for chronic obstructive pulmonary disease (COPD) treatment and disease management. In the 2021 GOLD report, changes mainly reflected treatment recommendations for patients with COPD who develop coronavirus disease 2019 (COVID-19), explained Antonio Anzueto, MD, in an interview with The American Journal of Managed Care®(AJMC®).

In addition to recommendations on COVID-19, the updated report highlights new research on COPD therapies, diagnosis, and rehabilitation programs. In this interview, Anzueto discusses the benefits of triple therapy for COPD, adherence issues patients may face, and the importance of correctly diagnosing the disease.

Anzueto, a professor of medicine at the University of Texas Health in San Antonio and clinician practicing pulmonary and clinical care, also serves as a member of the GOLD Science Committee.

The following interview has been edited for length and clarity.

AJMC®: What are some of the key updates made to the GOLD 2021 report, and why are they important?

Anzueto: Probably the main update in the report is having a section related to how COPD patients should be managed in the COVID-19 area. In this document, we emphasize the need to continue their current appropriate medication, to do the evaluations and diagnostic procedures. We recognize there are limitations in the use of spirometry due to COVID-19 and the risk for contamination. But that doesn't mean patients should not continue their appropriate therapies, as well as the prevention measurements, such as smoking cessation and pulmonary rehab. We specifically also recognize that COVID-19 may not finish the day the patient starts feeling better, that patients may have some long-term effects as part of COVID-19. We have a section on follow-up assessment for COPD patients after they develop COVID-19. The main areas are related to the management of COPD patients during the COVID-19 pandemic.

AJMC®: What are the goals for this year's GOLD report?

Anzueto: I think one of the main goals is going to be to fully understand how the pandemic is impacting our COPD patients. More importantly, how the vaccine will be able to protect these patients. We're looking forward as the vaccination is being implemented in older individuals, individuals with comorbid conditions, to understand the efficacy as well as the safety of the vaccine to protect our patients with COPD or with chronic lung disease.

AJMC®: What are some of the benefits of triple therapy in patients with COPD, and can you discuss any potential risks of pneumonia?

Anzueto: I think it's important to recognize that COPD today is a treatable condition. It's crucial to make a diagnosis to know what the disease is. And once we recognize the diagnosis, the important thing is to implement pharmacotherapy for these patients. Since the 2000s, beginning in 2010 to 2015, the standard of care has become the use of inhaled corticosteroids [ICS]/long-acting β2-agonist [LABA] in a fixed combination and the long-acting anticholinergics. Since triple therapy has become available in a single inhaler—first as a once-a-day with a combination of fluticasone, vilanterol, and formoterol, and later on with a twice-a-day formulation of budesonide, formoterol, and glycopyrrolate—we clearly have better opportunities for the management of our patients with COPD.

We have recognized also, for the last 15 years, that patients who receive inhaled corticosteroids are at an increased risk to develop pneumonia. Further studies in that area clearly recognized that the individuals who are sicker, and individuals who have very low eosinophil counts, are the ones at an increased risk of developing pneumonia. The clinical trials in patients on the triple therapy, the ICS/LABA/LAMA [long-acting muscarinic antagonist], versus the dual therapy LABA/LAMA without inhaled corticosteroids, demonstrated that there is an increased risk of pneumonia.

What I tell my patients is, yes, the potential risks have increased for pneumonia, but I'm doing everything that I can to prevent pneumonia. I try to be sure patients get up-to-date on influenza vaccinations. I try to keep them up-to-date on pneumococcal vaccinations both for the conjugated vaccine as well as the polysaccharide vaccine and [make sure] they are given at the appropriate time. Today we also understand that the diphtheria, pertussis, and tetanus [DPT] vaccine should be included in the management of patients with chronic lung diseases.

In a lot of the data on the risk of pneumonia and inhaled corticosteroids, the piece of data that is missing is the history of vaccination, especially pneumococcal vaccination. Clinical studies have demonstrated that pneumococcal vaccinations can give a significant protection especially to the serotypes included in the vaccine. I tell my patients, yes, you are at risk to develop pneumonia, but I'm trying to do everything that I can...This is a matter of risk/benefit. I believe that the benefit [of triple therapy] outweighs the risk primarily with the protection in reduction in exacerbations, improvement in quality of life, as well as improvement in lung function.

AJMC®: Studies on triple therapy have indicated it can result in a reduction in all-cause mortality when compared with dual and monotherapies. Is this finding a class effect?

Anzueto: I think it's hard to say if there is a class effect, if this is an effect of inhaled corticosteroids alone or this is an effect of the combination of medications. If we go back to 2000, there was a study called UPLIFT, and there were patients who were on ICS/LABA and they had the long-acting anticholinergic tiotropium added to the regimen. That study was versus placebo. There was a group of patients who were on ICS/LABA and placebo and patients who were on ICS and LAMA tiotropium. There was a significant reduction in mortality in the triple therapy group. I think, at the end of the day, there may be some effect with inhaled corticosteroids in the decreased mortality. But the benefit is being obtained and having the triple therapy, having the dual bronchodilators given together with inhaled corticosteroids, that would give the largest protection to the patients.

AJMC®: What are the main adherence challenges to triple therapy that your patients face?

Anzueto: For COPD, we have great medications available. As a matter of fact, 28 different medications have been developed over the last 15 to 20 years. And we can have the best medication in the world, but the patient cannot get it. That's a tremendous challenge. We are beginning to recognize that there are factors related to the individual, like their ability to generate enough inspiratory force to have a medication penetrate into the lungs, that is a very significant element, as well as coordination with the delivery systems, that [impact whether] they are able to get their medication. The GOLD committee has recognized, since 3 years ago we proposed in the algorithm of management that when the patient comes back to us for follow-up, and the patient tells us "I don't feel fine, I'm not doing well," before we jump into changing medication, adding or removing medications, we should address their ability to take the medication and their techniques. Having medications from different delivery systems—some dry powder, some are hydrofluoroalkane [HFA] formulation, some are soft mist, some are nebulized—these give us a very unique opportunity to tailor that delivery system to the patient's actual needs.

AJMC®: Can you elaborate on the role of critical errors in inhaler use and how these may impact patient outcomes?

Anzueto: When using the delivery systems and using the medication, certainly, there is a series of steps that the patient has to take in order to have the medication get into the lungs. Some of the challenges that we have are patients have to follow all those critical steps, because if they exhale too fast or inhale too slow, they don't follow those steps, they are at an increased risk of not getting the medication they need into the lungs.

One of the big challenges that we have today is trying to match the medication delivery to give them the appropriate medications…Some patients cannot do it in the powder form, it may be easy for them to do in an HFA form and vice versa. But it's very important, every time we assess our patients in our follow-up, to have them show us how they use the delivery system and remind them the appropriate way to use the delivery system.

AJMC®: According to the CDC, in 2011, about 5.4% of Texas residents surveyed had been told by a health care professional that they have COPD. In your experience, have you seen any trends in diagnoses in the state with the rising popularity of vaping or any external environmental hazards?

Anzueto: We have seen [trends] primarily from policies more related to cigarette smoking. We have seen a significant increase of patients diagnosed with COPD, because we are doing more spirometry [testing]. We're looking more at the management of their condition. So yes, we do see an increase in diagnosis of these patients.

AJMC®: Is there anything we didn't touch on that you'd like to include, or do you have any final thoughts you'd like to share?

Anzueto: It's very important to remind you that COPD is a treatable disease, but in order to treat it, we need to know what the patient has. One of the major concerns that I have is that many people have been labeled to have COPD never having [completed] spirometry, and if you do a spirometry test, they don't have COPD. So, the feeling that people happen to smoke, that doesn't mean they can develop or they're going to have COPD. Today, the gold standard is with the spirometry test… The important issue is we have to make a diagnosis of the disease because this is a treatable disease. If you make the right diagnosis, we have a tremendous opportunity to impact this patient's quality of life and lung function. Now we have seen with the recent publications of the triple therapy, you're not only reducing exacerbations, as well as improving quality of life and lung function, you may be reducing mortality, so we may impact the disease in ways we never suspected before.