Biologic Therapy for Asthma and COPD: Real-World Perspectives From APPs

Biologic therapy for severe asthma has become standard of care in pulmonary medicine, with approved agents across four mechanistic classes — anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-5 and anti-IL-5 receptor (mepolizumab, benralizumab, reslizumab, and depemokimab), and anti-thymic stromal lymphopoietin (tezepelumab) — supporting reductions in annualized exacerbation rates of 50% to 60% in appropriately selected patients.¹

The December 2025 FDA approval of depemokimab (Exdensur; GSK), a long-acting anti-IL-5 monoclonal antibody, introduced the first twice-yearly dosing interval in the class: SWIFT-1 and SWIFT-2 demonstrated 58% and 48% reductions, respectively, in annualized severe exacerbations versus placebo in patients aged 12 years and older with eosinophilic phenotype asthma.² Dupilumab's approved indication has also expanded into eosinophilic chronic obstructive pulmonary disease (COPD), with BOREAS and NOTUS demonstrating 30% and 34% reductions in moderate-to-severe exacerbations, respectively, alongside significant pre-bronchodilator FEV₁ improvements of approximately 83 mL over placebo at week 12 in patients with blood eosinophil counts of 300 cells/µL or greater on maximal triple therapy.³,⁴ These advances have broadened the biologic-eligible population substantially; yet prescribing rates remain far below the scale of the eligible burden, with access barriers, insurance restrictions, and Medicare cost constraints cited as primary drivers of the gap between evidence and clinical practice.

Against this backdrop, HCPLive convened a panel of advanced practice providers — nurse practitioners and physician assistants — representing pulmonary practices across Oklahoma for an in-depth discussion of real-world biologic prescribing in asthma and COPD. The forum was moderated by Samantha Bellinger, APRN, a pulmonary nurse practitioner with 11 years of experience at Integris Baptist Pulmonary Medicine in Oklahoma City, and included peers from Mercy Pulmonology, Breathe Oklahoma, Variety Care, and rural eastern Oklahoma practices. The panel's geographic and practice diversity — spanning urban academic-affiliated pulmonology, Cherokee Nation–served rural practices, private practice, and federally qualified health centers — provided an unusually granular view of how biologic therapy is integrated in communities where FeNO testing is frequently unavailable, oral corticosteroid overprescribing in primary care remains common, and formulary restrictions frequently determine agent selection as much as pharmacology does.

How GOLD 2025 and Mucus Plug Data Are Reshaping Biologic Selection in Eosinophilic COPD

The discussion was timely for several reasons. Updated GOLD 2025 guidelines formally incorporated biologic therapy into COPD escalation pathways, recommending dupilumab for patients with persistent exacerbations and blood eosinophil counts of 300 cells/µL or greater on maximal triple therapy — a change panelists described as directionally consistent with how many had already been prescribing, though the formal endorsement lends institutional support in peer persuasion.⁵ Simultaneously, the VESTIGE and CASCADE trials demonstrated mucus plug score reductions with dupilumab and tezepelumab, respectively, versus placebo — findings that several panelists have translated into clinical practice by preferring IL-4/IL-13–targeting agents over IL-5s in patients with a chronic bronchitis or mucus-predominant phenotype.⁶^,⁷ A novel, geographically specific concern emerged during the discussion: alpha-gal syndrome — a tick-transmitted sensitization to galactose-alpha-1,3-galactose with high prevalence in eastern Oklahoma — has not been evaluated in the context of biologic therapy, despite the fact that all current biologics are manufactured on Chinese hamster ovary cells that theoretically carry alpha-gal epitopes. Victoria Pierce, NP, whose practice serves the Cherokee Nation, reported empirically prescribing biologics in alpha-gal–sensitized patients with close monitoring and no observed reactions to date — a practice without any published guidance.

Insurance Coverage, Formulary Access, and Real-World Dupilumab Safety

Across the forum, panelists described a clinical environment in which biologic selection is driven at least as much by formulary access and insurance coverage as by pharmacologic reasoning. Dupilumab was the most frequently initiated agent across practices, valued for its broad indication, steroid-dependent indication, and comparative ease of approval in most commercial plans, though Blue Cross Federal was identified as a consistent denier. Pierce described mepolizumab as her most prescribed agent for the Cherokee Nation patient population due to its unrestricted formulary status — no prior authorization required — for approximately half her practice. Tezepelumab was positioned by the moderator as a functional Medicare substitute for dupilumab, given its ability to be administered at an infusion center for patients unable to use manufacturer copay assistance programs. Benralizumab was preferred for hypereosinophilic patients given its complete eosinophil depletion mechanism via apoptosis — considered particularly relevant in a patient population in which eosinophil counts in the thousands were described as disproportionately common — but faced inconsistent prior authorization outcomes in some rural areas.

Several real-world safety observations emerged that are infrequently highlighted in trial data: eyelid inflammation leading to dupilumab discontinuation in at least 2 patients in one practice; arthralgias significant enough to prompt cessation in a patient with coexisting rheumatologic disease; and concern raised by Burgess, drawing on inpatient clinical experience, about second-exposure anaphylactic or angioedematous presentations in patients re-initiated on dupilumab. As Pierce noted during the discussion: "With those really high eosinophils, I really like to go straight to Fasenra because of the apoptosis. It just completely depletes it all. I really like that. And then the dosing is convenient, but it's really hard for me to get approved in my area for whatever reason."

Depemokimab generated genuine interest but no enthusiastic first adopters among the panel. The key concern was not efficacy but risk management: with a 6-month pharmacologic duration that extends beyond the labeled dosing interval, a patient with an inadequate response or emerging adverse effect at 3 months cannot be re-dosed, switched to another agent, or have the drug effectively removed. The ideal candidate described by multiple panelists was an adherence-challenged patient — specifically, a college student who could receive reliably administered doses during clinic visits twice per year — rather than a biologic-naive patient in whom response is not yet established.

The COPD biologic discussion was framed largely around preventing fatal exacerbations rather than restoring spirometry, with panelists consistently pushing back against colleague skepticism anchored to FEV₁ alone. One panelist described a patient with a baseline FEV₁ of 21% and dependence on supplemental oxygen who achieved oxygen independence on dupilumab and subsequently traveled by motorcycle — a case that has since informed her broader approach to COPD biologic prescribing. Panelists identified pulmonary rehabilitation access, practical smoking cessation infrastructure beyond the "stop smoking" recommendation, and a neutrophil-targeting agent that does not compromise infection defense as the most meaningful unmet needs in their predominantly rural, underserved patient populations.³^,⁴

References

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2025. Accessed June 2026. https://ginasthma.org

2. Jackson DJ, Wechsler ME, Menzies-Gow A, et al; SWIFT-1 and SWIFT-2 Investigators. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. 2024;391(24):2337–2349. doi:10.1056/NEJMoa2406673

3. Bhatt SP, Rabe KF, Hanania NA, et al; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023;389(3):205–214. doi:10.1056/NEJMoa2303951

4. Bhatt SP, Rabe KF, Hanania NA, et al; NOTUS Study Investigators. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N Engl J Med. 2024;390(24):2274–2283. doi:10.1056/NEJMoa2401304

5. Global Initiative for Chronic Obstructive Lung Disease. GOLD 2025 Report: Global Strategy for the Diagnosis, Management, and Prevention of COPD. Updated 2025. Accessed June 2026. https://goldcopd.org

6. Maspero J, Laidlaw TM, Onoue M, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2025. doi:10.1016/S2213-2600(24)00362-X

7. Nordenmark LH, Hellqvist Å, Emson C, et al. Tezepelumab and mucus plugs in patients with moderate-to-severe asthma. NEJM Evid. 2023;2(10):EVIDoa2300135. doi:10.1056/EVIDoa2300135