Payers, Eosinophil Thresholds Shape Who Gets a COPD Biologic

Patients with chronic obstructive pulmonary disease (COPD) now have 2 biologic treatment options that are incorporated as escalation pathways for eosinophilic disease in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. However, with these guidelines regulating the 2 biologic therapies, patients and physicians are looking ahead to how payers will manage these relatively new therapies.

In light of COPD Awareness Month, clinicians should closely examine the potential outcomes of payer management of this disease. Many have expressed the challenges associated with treating patients with COPD, particularly stressing cost and logistical concerns like eosinophil thresholds, step therapy, and documentation rules that determine patient eligibility.

Currently, biomarker-driven eligibility, specifically eosinophil, fractional exhaled nitric oxide (FeNO), and IgE tests, is noninvasive, affordable, and can be performed at the majority of hospitals, Francesca Puggioni, MD, an adjunct professor of respiratory diseases at Humanitas University and vice director of the Personalized Medicine Asthma and Allergy Clinic at Humanitas in Milan, Italy, said in an interview with The American Journal of Managed Care^® (AJMC^®) on research presented at the European Respiratory Society (ERS) 2026 International Congress. But a gap remains in relying solely on single biomarker tests as opposed to a “combined score of biomarkers” to help clinicians better understand the severity of a patient’s disease and inform treatment decisions and management.¹

How Eosinophil Thresholds Became the Gatekeeper for COPD Biologics

The GOLD 2025 and 2026 guidelines set separate thresholds for each biologic approved to treat COPD, which payers have adopted as hard cutoffs for patient eligibility.^2,3 The threshold for dupilumab (Dupixent; Regeneron/Sanofi), approved September 27, 2024, is set at 300 cells/µL, and the threshold for mepolizumab (Nucala; GSK), approved May 22, 2025, is set at 150 cells/µL.^2-5

Because of feasibility and cost, eosinophils have become a standard biomarker of eligibility, but they are not the only biomarker for COPD.¹

“We keep saying that in COPD we don't have biomarkers, but the truth is that we have a lot of biomarkers that have been published in good papers,” Francesca Polverino, MD, PhD, a physician-scientist and tenured Lester and Sue Smith Professor of Medicine at Baylor College of Medicine, said in an interview with AJMC about her session presentation on COPD exacerbation severity and treatment escalation. “What we don't have are clinical trials that leverage these biomarkers to better understand how to categorize patients for clinical trials.”⁶

Polverino cited club cell protein 16 (CC16) as a COPD biomarker. Low levels of CC16 are associated with fast lung function decline, and although this association has been confirmed by Polverino herself and other research groups in more than 8 COPD cohorts, CC16 is not actively leveraged in clinical trials.⁶

Yet when it comes to the use of steroids, eosinophil count remains the primary biomarker, Polverino said.⁶

In an interview with AJMC on the COPERNICOS trial presented at ERS, Jorgen Vestbo, MD, a professor of respiratory medicine and an honorary consultant at the Northwest Lung Centre, Manchester University Hospital, stressed that the biomarker must be measured over time, underscoring the fragility of relying on a single eosinophil reading to determine patient eligibility.⁷

Documentation Gaps and Treatment Delays Stall Biologic Access

Another requirement for prior authorization or patients’ eligibility for COPD biologics is documented exacerbation history. GOLD guidelines suggest treatment escalation for those who’ve experienced at least 1 moderate exacerbation. But the lack of a definition for what constitutes a severe exacerbation makes it difficult for clinicians to determine which patients are eligible or require treatment escalation.⁸

Polverino, whose county hospital patients are largely uninsured or on Medicare or Medicaid, noted that exacerbations often occur in primary care offices.⁸

“How do we call this exacerbation if it's not even recorded in the ER [emergency room]?” Polverino said. “This is the first thing that we should have clarity on. We should get a better definition of moderate versus severe exacerbation because I think we're not there yet.”⁸

Gaps in definition could delay necessary treatment initiation or escalation. Related ERS data showed that delaying dupilumab initiation beyond 90 days after a severe asthma exacerbation was linked to a 32% increase in predicted cumulative asthma-related medical costs by 1 year. Although the observational study was in asthma and excluded biologic costs, the example highlights the importance of early diagnosis and treatment initiation across pulmonary disorders.⁹

There is “…also some delay from the health care system: getting approvals, cost reimbursement, and prior authorization,” which can further hinder patient access to treatment, Nicola Hanania, MD, associate professor of medicine in the section of pulmonary and critical care medicine and director of the American Lung Association Airways Clinical Research Center (ACRC) at Baylor College of Medicine, said in an interview with AJMC about his study on asthma-related health care utilization presented at ERS.⁹

Delayed access to treatment could also result in disease progression surpassing the point at which biologics could be most beneficial.

“When you get to GOLD 3 and GOLD 4, the lung tissue is really not in a good shape to respond to anything,” Polverino said.⁸

Toward Combined Biomarkers and Multidisciplinary Care

Aside from COPD-specific biomarkers, multidisciplinary care could also help inform disease severity. Puggioni’s emphasis on a combined score of biomarkers extends to the help of other specialists, like ear, nose, and throat doctors, who are used to performing biopsies on polyps, or dermatologists or gastroenterologists for eosinophilic esophagitis.¹

“I think that we should develop algorithms that are a little bit sophisticated, not in the biomarkers by themselves, but in the relationship between them,” she explained. “The research in this case has a long way to go.”¹

Determining whether a patient should receive a biologic for COPD should involve multiple specialists, she emphasized.

“We decide which is the best approach, and this allows us to understand which biologics and which dosage of biologics for which disease, and we train the patient on this situation,” Puggioni said.¹⁰

The clinicians AJMC spoke with at ERS agreed that diversifying the clinical use of biomarkers for patients with COPD could help improve access and treatment management. Polverino also pointed to radiology, such as mucus plugs, which she said could be “an excellent biomarker for COPD.”⁶

“If you tell me 10 years from now, I can see how the patient with COPD will be stratified based on blood biomarkers or other accessible biomarkers, like sputum or CT scan biomarkers, with what we call multi-omic integration,” Polverino said. “This is a multi-scale integration of omics technologies, which can be proteomics, breathomics, or radiomics—all these technologies that are now in the works and have been assessed by research teams like mine will eventually be validated and integrated.”⁶

References

1. McCrear S, Puggioni F. Closing the gap between trials and real-world care. AJMC. September 10, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/closing-the-gap-between-trials-and-real-world-care

2. Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to COPD diagnosis, management, and prevention: a guide for health care professionals, 2025 report. November 2024. Accessed November 10, 2026. https://goldcopd.org/wp-content/uploads/2024/11/Pocket-Guide-2025-v1.0-New-Format-15Nov2024_WMV.pdf

3. Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to COPD diagnosis, management, and prevention: a guide for health care professionals, 2026 report. November 2025. Accessed November 10, 2026. https://goldcopd.org/wp-content/uploads/2026/01/GOLD-Pocket-Guide-2026-v1.1-20Nov2025_WMV2.pdf

4. McCormick B. FDA approves dupilumab as first biologic treatment for COPD. AJMC. September 27, 2024. Accessed November 10, 2026. https://www.ajmc.com/view/fda-approves-dupilumab-as-first-biologic-treatment-for-copd

5. McCormick B. FDA approves mepolizumab as first once-monthly biologic for COPD with eosinophilic phenotype. AJMC. May 22, 2025. Accessed November 10, 2026. https://www.ajmc.com/view/fda-approves-mepolizumab-as-first-once-monthly-biologic-for-copd-with-eosinophilic-phenotype

6. McCrear S, Polverino F. Beyond eosinophils: COPD biomarkers and overtreatment risk. AJMC. September 14, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/beyond-eosinophils-copd-biomarkers-and-overtreatment-risk

7. McCrear S, Vestbo J. COPERNICOS trial: eosinophil-guided ICS reduction safe in COPD, Vestbo says. AJMC. September 6, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/copernicos-trial-eosinophil-guided-ics-reduction-safe-in-copd-vestbo-says

8. McCrear S, Polverino F. GOLD’s COPD escalation rule draws debate: Francesca Polverino, MD, PhD. AJMC. September 11, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/golds-copd-escalation-rule-draws-debate-francesca-polverino-md-phd

9. McCrear S, Hanania N. Delayed dupilumab raises asthma costs 32%: Nicola Hanania, MD. AJMC. September 16, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/delayed-dupilumab-raises-asthma-costs-32-nicola-hanania-md

10. McCrear S, Puggioni F. Why multidisciplinary care drives COPD biologic selection. AJMC. September 8, 2026. Accessed November 10, 2026. https://www.ajmc.com/view/why-multidisciplinary-care-drives-copd-biologic-selection