The introduction of two new biologic drugs for chronic obstructive pulmonary disease (COPD) has reshaped treatment options, but their effectiveness now depends as much on insurance policies as on medical evidence. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines now classify these therapies as escalation treatments for patients with eosinophilic COPD—a condition marked by raised white blood cells tied to inflammation. However, insurers have adopted strict eligibility rules that may restrict access for those who stand to benefit most from these expensive medications.
Regulatory approvals for these drugs arrived in rapid succession: dupilumab (Dupixent) received clearance in September 2024, followed by mepolizumab (Nucala) in May 2025. Both medications target eosinophilic inflammation, but their use depends on a single blood test result. For dupilumab, the cutoff is 300 cells per microliter of eosinophils; for mepolizumab, it drops to 150 cells per microliter. These thresholds, now embedded in updated GOLD guidelines, have become the standard for insurance coverage, turning a biological marker into a barrier for eligible patients.
While eosinophil testing is widely available, affordable, and simple to perform, it is not the only relevant biological indicator. Studies have identified club cell protein 16 (CC16) as another predictor, with low levels associated with faster declines in lung function. Yet this marker is not yet incorporated into treatment decisions or payer policies. Francesca Polverino, MD, PhD, a respiratory specialist at Baylor College of Medicine, explained that clinical trials continue to prioritize eosinophils despite evidence that COPD inflammation involves more complex factors. The reliance on a single test creates practical challenges, as patient counts can vary over time, potentially disqualifying them from treatment even when their disease remains active.
Insurance rules block timely COPD treatments
Jorgen Vestbo, MD, a respiratory professor at Manchester University Hospital, warned that biomarkers should be monitored continuously rather than treated as a one-time eligibility check. The risk, he noted, is that patients whose counts fall below the threshold could lose access to biologics when their condition still requires intervention. Documentation requirements further complicate matters, as insurers often demand proof of recent moderate or severe COPD exacerbations. However, the GOLD guidelines do not define what constitutes a severe episode, leaving many exacerbations—particularly those treated in primary care—unrecorded. Polverino, who treats predominantly uninsured and Medicaid patients, pointed out that without standardized definitions, clinicians struggle to demonstrate eligibility, delaying treatment initiation.
Treatment delays carry significant consequences. Research in asthma, where similar biologics are used, shows that waiting more than 90 days after a severe exacerbation to start treatment increases medical costs by 32% within a year. The same principle applies to COPD: prolonged delays make it harder to halt disease progression. By the time patients reach GOLD stages 3 or 4, their lung damage may be too advanced for biologics to produce meaningful benefits.
Administrative hurdles also hinder access. Prior authorization processes, cost reimbursement delays, and step therapy requirements create unnecessary delays. Nicola Hanania, MD, director of Baylor’s Airways Clinical Research Center, described the systemic friction: delays in approvals, reimbursement, and prior authorization compound the challenges for patients already struggling with COPD. These bureaucratic obstacles can determine whether treatment arrives in time to prevent further decline.
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Single biomarkers fail to capture COPD complexity
The conflict between clinical need and payer restrictions extends beyond access; it reflects differing understandings of COPD. Current guidelines treat eosinophil counts as a binary factor, but inflammation in the disease is more varied. Some patients might benefit from a combined biomarker approach, integrating eosinophils with other markers such as CC16, fractional exhaled nitric oxide (FeNO), or even imaging evidence like mucus plugs. Francesca Puggioni, MD, of Humanitas University in Milan, argued that treatment algorithms should consider multiple factors rather than relying on a single lab result. This approach would better match patients to the right biologic and dosage.
Collaboration across specialties could help address these gaps. Clinicians treating eosinophilic esophagitis already use biomarkers to guide therapy, often involving dermatologists and gastroenterologists alongside pulmonologists. Puggioni suggested that COPD management could adopt a similar team-based model, where specialists contribute to patient assessments. However, she acknowledged that the research in this area remains in early stages. For now, the lack of multi-marker algorithms forces clinicians to make treatment decisions with incomplete data.
Beyond eosinophils, other biological markers offer additional insights into COPD severity. Low levels of CC16 correlate with faster deterioration, yet it is not included in current treatment guidelines. Polverino emphasized that clinical trials have not fully incorporated this or other markers like FeNO or immunoglobulin E (IgE), despite their demonstrated value. The absence of these indicators in payer decisions highlights a broader issue: treatment protocols still depend on a single lab value, even when research confirms that COPD inflammation is more complex.
Team-based care could transform COPD therapy
Multidisciplinary care could help overcome some of these limitations. Puggioni advocates for a team-based approach, where pulmonologists, allergists, dermatologists, and gastroenterologists collaborate on patient assessments. In eosinophilic esophagitis, for instance, specialists from multiple fields work together to tailor biologic therapies based on endoscopic findings and biomarker profiles. A similar model for COPD could improve treatment matching, determining not just eligibility but also the most effective biologic and dosage. Puggioni stressed that algorithms should evaluate relationships between biomarkers, patient history, and symptoms rather than relying on isolated values.
Barriers to Treatment Access and Alternative Biomarkers in COPD Care
Insurance policies for the two new biologic therapies have introduced additional challenges beyond clinical eligibility. Payers are still determining how to cover these treatments, particularly for patients with limited insurance options like Medicare or Medicaid. Hospitals serving these populations report that exacerbations frequently occur in primary care settings, yet these episodes are often not formally documented in emergency rooms. This lack of standardized recording creates uncertainty over whether an exacerbation meets the criteria for severe disease, which insurers require to authorize treatment.
