Evolving Standards and Emerging Treatments in COPD Care

AJMC®: What recent developments in the therapeutic landscape of chronic obstructive pulmonary disease (COPD) do you think have the greatest potential to shift how treatment is managed?

Dr Martinez: Globally, care of patients with COPD generally follows the recommendations of the GOLD Report (the Global Initiative for Chronic Obstructive Lung Disease Global Strategy for Prevention, Diagnosis and Management of COPD). The 2025 iteration (GOLD 2025) clarified 1 point of consternation and recommended placement of 2 new therapeutic options into the algorithm for follow-up care.

First, clinical trial evidence shows that inhaled triple therapy with a LAMA plus a LABA plus an ICS (a long-acting muscarinic antagonist, a long-acting β₂-agonist, and an inhaled corticosteroid) is more effective than dual combinations like LAMA/LABA or LABA/ICS. Yet many clinicians still prescribe dual therapy, sometimes influenced by payer restrictions or formulary tiering. To address this, GOLD 2025 provided practical guidance: If a patient on LABA/ICS is stable, it may be reasonable to continue that regimen. However, if symptoms persist or blood eosinophil counts (BEC) are elevated, escalation to triple therapy should be considered. Conversely, in patients whose disease has been well controlled for about 1 year, de-escalating therapy to LABA/LAMA may also be appropriate.

The second major update added dupilumab as an option for patients currently on triple therapy who continue to experience exacerbations and have an elevated BEC. In this population, dupilumab was associated with reduced exacerbations and improvements to lung function, symptoms, and quality of life.

The last major update incorporated ensifentrine, a PDE3/4 inhibitor, into the GOLD recommendations. While not studied extensively in high-risk populations, it was associated with significant benefit in terms of bronchodilation and select patient-reported outcomes, making it a reasonable add-on for patients with persistent dyspnea despite bronchodilator therapy.

AJMC®: How do you see dupilumab and ensifentrine fitting into existing treatment pathways and access frameworks, such as step therapy or prior authorization?

Dr Martinez: Integrating dupilumab and ensifentrine into payer frameworks will require clearly defined patient populations and clinical criteria to align prescriptions with those patients most likely to benefit from these treatments according to the clinical trial data.

For dupilumab, the trial program evaluated this drug as an add-on in patients who continued to have exacerbations despite maximal inhaled therapy and whose BEC was elevated. That defines a clear eosinophilic COPD subgroup in which dupilumab was associated with clinically meaningful benefits. As a clinician speaking on ideal payer policies, my recommendation would be to offer coverage within this narrowly defined patient population while making some allowances for patients who are unable to tolerate maximal inhaled triple therapy. Dupilumab is a high-cost biologic, so coverage policies will need to balance clinical value and affordability. The recently approved biologic mepolizumab will likely require similar consideration, but the GOLD Report has yet to reconcile the mepolizumab clinical trial data into a treatment recommendation.

Ensifentrine is different, because those trials enrolled a generally less exacerbation-prone population, and its nebulized method of administration is more restrictive. I consider ensifentrine’s price point to be high for a step-up therapy, but, ultimately, GOLD 2025 positioned this agent as add-on therapy in patients with persistent breathlessness, as close to the trial-defined populations as possible. Clinicians and managed care decision-makers need to understand the expense and restrictive administration method of this medication and align prescriptions with patients’ symptoms rather than as a broad exacerbation-prevention therapy.

AJMC®: When considering whether to incorporate new COPD treatment options into your prescribing practices, what data do you consider most important?

Dr Martinez: As a clinical trialist, I am a strong believer that the optimal data comes from randomized, placebo-controlled trials followed by support from real-world or nonrandomized studies.

As an example, for years, there had been failures trying to apply targeted biologic therapies to broad populations of patients with COPD, but then the dupilumab studies came around and were highly successful. What made the dupilumab studies stand out were their highly selective inclusion criteria focused on a narrow patient population with an eosinophilic endotype. The lesson for community clinicians is that they should not apply these treatments broadly, because that has been attempted and has failed. Instead, the high cost of these new treatments is warranted within the narrowly defined patient populations of the clinical trials.

This reflects a broader strategy being attempted by GOLD—moving toward treatment personalization. An old ABCD treatment initiation schema was a crude version of personalization that accounted for exacerbation history and patients’ current symptoms. We now use an ABE schema as a precision-guided approach informed by both clinical features and a biological marker. This transition was only possible because data emerged regarding eosinophils and the use of inhaled corticosteroids. With biologics entering the COPD treatment space, there is an opportunity for further refinement, highlighting the arrival of precision, personalized therapy for patients with COPD. Because of the expense and complexity of these new therapies, it is critical to prescribe them only to those patients most likely to benefit.

AJMC®: What factors should payers and providers weigh to ensure these treatments are used appropriately?

Dr Martinez: The US marketplace has unique fiscal pressures for private payers and for Medicare. These newer biologics are expensive, so it’s appropriate to apply some restraint and clear prescribing criteria.

We know from past experience that the broad use of biologics in patients with COPD resulted in disappointing trial outcomes. Now, we have seen their clinical benefit in narrower patient populations as defined in the pivotal trials. Therefore, payers would be justified in requiring adherence to those trial-based criteria. Clinicians and payers working together to target use in the populations most likely to benefit is where the cost–benefit balance is most favorable.

AJMC®: Because these new COPD medications involve less common routes of administration, what are the practical considerations for payers and providers to facilitate access?

Dr Martinez: Each of these new therapies has unique challenges, because each moves beyond the traditional handheld inhaler approach that clinicians and patients know well. With ensifentrine, there is some complexity, because patients must sit for the duration of the nebulization, and not everyone prefers to stay still for that long. That said, patients in the US seem more familiar and willing to use nebulizers than do patients in other parts of the world, and those who have tried ensifentrine tend to report noticeable improvements to their symptoms that increases their willingness to commit to nebulization.

The biologics dupilumab and mepolizumab are administered via self-injection, and the complexity there is that not every patient is enthusiastic about an injection. There are some changing attitudes thanks to the widespread adoption of self-administered injectables in other therapeutic areas; GLP-1 therapies have been transformative in that respect. Regardless, self-injection is not as simple as handing a patient an inhaler at the pharmacy. There need to be mechanisms in place to ensure that patients have the education and support to administer biologics safely and appropriately.

AJMC®: Are you aware of any payer restrictions on coverage of nebulizers for inhaled therapies?

Dr Martinez: Historically, many COPD specialists could prescribe nebulized bronchodilators or inhaled steroids, because payers, driven largely by Medicare policy, reimbursed the nebulizer device under durable equipment benefits, and the device manufacturers would include generic medications with the purchase of the device.

With ensifentrine, the expense of this medication makes those considerations more complex. There is an intricate preapproval process typically required. Even then, patients may face substantial co-payments. While ensifentrine can be highly effective for certain individuals, the combination of cost, coverage requirements, and administrative steps can complicate access.

AJMC®: Have you encountered patient populations who may have difficulty administering the biologic medications, since they are self-injected?

Dr Martinez: Yes, some patients are uncomfortable with the idea of self-injection. That hesitation has decreased somewhat with the broader experience of self-administered therapies like GLP-1 inhibitors, but there are still patients who are nervous about injections or skeptical of medicine in general.

Another challenge is that the benefits of these long-acting biologics aren’t immediately apparent—they primarily reduce the risk of future exacerbations rather than provide an instant effect. This can make it harder for patients to understand the rationale for frequent injections, and it may impact long-term adherence. Effective communication is essential to help patients understand why these medications are being prescribed.

AJMC®: Is there specific clinical or economic evidence that you would prefer to see before recommending new medications to your patients?

Dr Martinez: From an economic standpoint, the strongest argument for using higher-cost medications is patients at highest risk for health care utilization. For example, patients with a history of exacerbations or prior hospitalizations represent a high-cost population. In these individuals, even an expensive therapy can be justified economically if it reduces the risk of future hospitalizations or other acute events.

Similarly, patients who experience frequent exacerbations requiring ED (emergency department) visits or unscheduled office visits may also benefit economically from these therapies, particularly if they meet biologic-specific criteria such as elevated eosinophil counts while on optimized inhaled therapy.

One potentially expanding consideration involves workplace productivity. For younger, working patients who experience exacerbations that don’t lead to hospitalization but do result in missed workdays, there may be a tangible economic benefit for employers to support use of these higher-cost therapies. By reducing work absenteeism, biologics or nebulized therapies could demonstrate value in ways that extend beyond traditional health care cost metrics.

AJMC®: How well does GOLD 2025 align with real-world patient populations?

Dr Martinez: Overall, GOLD2025 is a well-written, thorough document, but it is designed to be globally applicable, not just focused on the US population. That can make it challenging to align recommendations with the clinical realities of diverse geographic regions, because recommendations for different types of patients must be generalizable across very different health care systems. I recall presenting a case at the World Health Organization advocating for long-acting bronchodilators to be added to the list of essential medicines. Afterward, representatives from other countries pointed out that adding such therapies would come at the expense of other essential interventions, like childhood vaccinations. GOLD has to approach COPD treatment recommendations, balancing that level of global application and practicality.

Clinicians may also find it challenging to navigate the overall length and density of the document. To assist, the pharmacologic initiation and follow-up algorithms all appear as simplified, straightforward figures that can be applied in various health care settings among diverse patient populations. GOLD also recently updated its corresponding website to make treatment algorithms easier to maneuver and quickly reference.

A final, paradoxical challenge is GOLD’s heavy reliance on clinical trial data, most of it industry-supported. This creates a feedback loop: Regulatory bodies align clinical trial designs with GOLD criteria, which, in turn, limits the scope of evidence for newer or more innovative therapies. As a result, GOLD can struggle to provide evidence-based guidance for emerging disease-modifying drugs or therapies targeted to earlier-stage or younger populations, making it harder for clinicians to apply these recommendations to real-world patients.

AJMC®: How does the design and structure ofGOLD 2025 affect the ability of care providers to effectively implement COPD treatment?

Dr Martinez: GOLD guidelines have always tried to balance being a global document with providing practical guidance, especially for primary care clinicians, who manage most cases of COPD. Recent updates provided clearer guidance on when and how to evaluate patients using spirometry and simplified some of the initial treatment recommendations. One example is the change from an ABCD intervention schema to the ABE schema. That made it easier for clinicians to evaluate patients and initiate therapy. Where things remain more complicated are in follow-up decisions and in applying newer or more complex therapeutic approaches. That’s unavoidable to some extent, given the nature of the disease and treatments.

Another important evolution in GOLD has been recognizing the reality of comorbidities. Most patients don’t just have COPD; they also live with cardiovascular disease, diabetes, hypertension, and other conditions. Primary care clinicians are responsible for caring for the patient holistically, not just the COPD in isolation. Based on input from those clinicians, the most recent GOLD Report has expanded its focus on comorbidities—particularly cardiovascular disease—to provide a more useful framework for real-world patient management.

AJMC®: From a managed care perspective, what strategies help ensure that patients with COPD and comorbidities achieve optimal outcomes?

Dr Martinez: One of the positive developments in the US health care system has been a growing recognition of the need to coordinate care across specialties and practitioners. For patients with COPD, outcomes are often determined not just by their lung disease but by comorbid conditions, such as cardiovascular disease or diabetes. In fact, many patients with COPD face hospitalization or death because of complications from comorbidities rather than COPD itself.

From a managed care perspective, the goal is to keep patients healthier, out of the hospital, and productive. That requires closer collaboration among pulmonologists, cardiologists, endocrinologists, and other specialists, with the primary care clinician at the center of coordination. Payer policies that support and enable this kind of integrated, team-based approach are critical to optimize outcomes in patients with COPD and complex comorbidities.

AJMC®: Are you aware of any actual or perceived situations in which the guidance from GOLD 2025 conflicts with the treatment recommendations for comorbid conditions? If so, how do you navigate those situations?

Dr Martinez: I would not describe these situations as conflicts. Rather, different guidelines take their own view of patients’ overall health. The classic example is β-blockers. For a long time, GOLD considered β-blockers associated with airflow limitation and more intense COPD symptoms. But after a series of large studies, GOLD recognized that using selective β-blockers was beneficial to cardiac outcomes, and any airflow limitation they caused was insufficient to consider withholding them due to pulmonary considerations. This allowed cardiac and pulmonary specialists to better integrate their thinking. In fact, the GOLD Science Committee and a group of cardiologists recently published a synthesis document to generate a more cohesive therapeutic strategy for patients with cardiac and pulmonary comorbidities.

That said, there is still some uncertainty in specific high-risk cardiovascular populations, particularly those at risk of arrhythmias. These patients are often excluded from clinical trials of inhaled therapies, so questions remain regarding the safety of long-acting bronchodilators in those populations. Effective care in these scenarios requires close communication and consensus within a multidisciplinary care team, often with a primary care physician in the critical coordination role.

Increasingly, managed care organizations are also bringing in case managers or developing multispecialty programs to support patients with multiple chronic diseases, like COPD and heart failure. These are some of the highest-risk, highest-cost populations in the US, and care models that operationalize coordinated management have shown real success.

AJMC®: What do you think are the remaining gaps in caring for patients with COPD?

Dr Martinez: One major gap is implementing disease-modifying therapies in younger patients whose disease is in its earlier stages. There’s a big push to test therapies in that population, with the goal of preventing more severe forms of COPD 10 years down the line. To support that, we need simpler, more practical approaches to case finding and diagnosis in primary care. Making COPD identification as streamlined as possible will be key.

On the more severe end of the COPD spectrum, the treatment options to improve outcomes are currently limited. For those patients, I expect more therapies to become available soon, particularly with biologics emerging with COPD indications; currently, however, there are few disease-modifying therapies for advanced COPD.

Likewise, among patients with COPD and comorbidities, much of the current focus is on personalized treatment for patients with cardiovascular comorbidities, but there is an argument that psychiatric and other comorbidities have been neglected. As shared clinics and strong, coordinated care communication systems proliferate, I expect there will be tighter integration between specialists and primary care. For now, that level of personalized treatment is in its infancy.

AJMC®: Are there any transformative changes to COPD care strategies that you would anticipate in the coming years, whether in terms of drug development or systemic policy?

Dr Martinez: First, I think case finding will become much more cohesive and fully embedded into primary care, enabling earlier and more accurate diagnosis. That’s going to open the door to implementing disease-modifying therapies much earlier in the disease course, potentially even in people as young as their twenties. That kind of early intervention could be revolutionary.

Second, as more biologics enter the space, we’ll need to figure out how best to use them, and I expect research or real-world evidence to direct combinations of these therapies. My hope is that COPD will follow the same trajectory as asthma, where the field has been completely transformed in just the past 5 years by inhaled therapies and biologics. I think COPD could be in the same position within the next 4 to 5 years. It may become more complex to determine which biologic to use and when, but, as the asthma community has shown, it’s possible to navigate that complexity effectively.

Overall, I would say that COPD care is currently experiencing a revolution in a way that will be very beneficial to patients. Caring for patients these days looks very different than it did 5 years ago, and I expect that 5 years from now, patient care will continue to improve.