Recent data are helping reshape how triple therapy should be used in the management of chronic obstructive pulmonary disease (COPD) in patients with a history of a moderate or severe exacerbation. Identifying those patients with COPD who may benefit from triple therapy is based on current guideline recommendations, with key clinical factors and biomarkers guiding treatment decisions.

Triple therapy with ICS agents, LAMAs, and LABAs is the cornerstone of treatment in a specific subset of patients with COPD. We have to be careful, as this treatment regimen is not for all patients, but it can be extremely efficacious in the subset of patients with the specific endophenotype of high type 2 inflammation, as demonstrated by high eosinophils, and frequent exacerbations. Sometimes we also prescribe triple therapy to patients with a high symptom burden.

The latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD report suggests that triple therapy should be considered in conjunction with the patient’s exacerbation history. According to the GOLD report, patients with blood eosinophil counts of 300 cells/μL or higher and frequent exacerbations—and now even 1 moderate or severe exacerbation is considered too many—should strongly be considered for triple therapy. Patients on LAMA and LABA therapy who have blood eosinophil counts of 100 cells/μL or higher and at least 1 moderate or severe exacerbation may also benefit from triple therapy, according to the report. The added effect of ICS therapy seems to be an approximately 25% extra reduction in exacerbation frequency. Of course, adding ICS therapy can come with some side effects. The biggest concern is pneumonia, relatively minor side effects include thrush, and longer-term side effects include glaucoma, cataract, and osteoporosis.

Recently, there has been a trend toward the overprescription of ICS-containing treatments and guideline-discordant therapy, particularly with the advent of single-inhaled triple therapy. I think that we have to be careful to match the patient’s endophenotype to the appropriate therapy. In an electronic medical record survey, up to 60% of patients who were initiated on triple therapy had either no history of exacerbations documented or only 1 mild exacerbation, which is discordant with GOLD report recommendations. I think that we have to be aware of the guidelines and make sure that the treatment is consistent with the guidelines.

We have been really fortunate to have some large clinical trials evaluating triple therapy in COPD, where I think we were expecting to see exacerbation reductions using this regimen but probably not the mortality benefit that was seen. We had evaluated for mortality benefit so many times and had not achieved it previously, so I think that, with the newer data, everyone was pleasantly surprised that mortality benefit was demonstrated. The weight of the evidence now suggests a broad swath of benefits with triple therapy in appropriate patients who are symptomatic with frequent exacerbations. These potential benefits include reductions in mortality and cardiovascular events.

I think that the onus is really now on clinicians to be constantly reevaluating the data and updated recommendations. GOLD recently updated its report to indicate that “high risk” should now be considered as having 1 or more moderate or severe exacerbation(s) in the past year, so I think that people are moving toward the earlier initiation of triple therapy in general.

One of the things that has become clear over the years is that steroids should only be used in a proportion of individuals. When you look at the risks and benefits of therapy, it is clear that there are both a risk and a benefit to steroid use in COPD, and that balance varies by person. The GOLD report does try to provide guidance to clinicians on how best to weigh that risk vs benefit.

The determination of COPD severity used to be based on clinical features. You would have a certain series of clinical features, and you would make a decision based on that. What has happened more recently has been the inclusion of a type 2 inflammatory biomarker. The GOLD report embraced the concept that, if you were able to identify a type 2 inflammatory pattern with a simple biomarker such as circulating eosinophil count that proved to be predictive of steroid response, this would allow for the further precision of therapeutic decision making, in addition to clinical features.

The most recent changes in the GOLD report have included this concept of what is considered clinically to be high risk. It turns out that if you have had 1 or more moderate or severe exacerbation(s) in the past year, you have a higher risk, and the treatment response with ICS therapy is very similar. Within the construct of now including clinical presentation, at least 1 moderate or severe exacerbation, and a blood eosinophil count for an individual patient, we currently have probably the best approach that we can to optimize what patient population will experience the greatest benefit from using triple therapy with the least amount of risk.