Clinical Forum Weighs in: Biologic Selection in Asthma and COPD

Biologic therapy for obstructive airway disease has moved well beyond a single anti-IgE option, with 7 agents now available for severe asthma and 2 approved for chronic obstructive pulmonary disease (COPD) with type 2 inflammation. Recent additions include FDA approvals of dupilumab and mepolizumab for eosinophilic COPD and of depemokimab, a twice-yearly anti-interleukin (IL)-5 agent, for severe eosinophilic asthma.1-4 With more options available, clinicians face growing questions about when to escalate, how to choose among agents, and how payer policies shape those decisions.

On September 17, 2026, Joseph Khabbaza, MD, a pulmonologist at Cleveland Clinic, moderated a virtual clinical forum on type 2 inflammation and biologic therapy in asthma and COPD. Participants included pulmonologists, critical care physicians, physician assistants, and a critical care pharmacist from Cleveland Clinic and other health systems in Ohio and California. The discussion covered biomarker use, oral corticosteroid (OCS) thresholds, agent selection, and unmet needs in COPD.

Biomarkers and OCS Thresholds for Biologics in Asthma

Participants described routinely documenting blood eosinophil counts at the first visit, even in patients with stable disease, so that a biologic option is established if control worsens. Several noted that fractional exhaled nitric oxide offers useful clues but is not available at every facility and is rarely sufficient on its own for payer approval. For patients referred on chronic steroids, whose eosinophils are often suppressed, participants said they rely on historical counts or on exacerbation history to support coverage.

Most participants cited 2 or more OCS-treated exacerbations per year as their trigger for considering a biologic. Some described lower thresholds for younger patients, given decades of potential cumulative exposure, and 1 participant said a cumulative dose of approximately 500 mg of prednisone in a year would prompt escalation. Participants also noted that steroid courses prescribed in urgent care or other health systems often go undocumented, and that not every course reflects a true exacerbation.

Beyond exacerbations, participants described pursuing biologics for patients with persistent daily symptoms or low FEV1 who do not exacerbate frequently, while acknowledging that coverage is harder to obtain. Several stressed confirming the diagnosis first, citing mimickers such as subglottic stenosis.

Selecting Among Asthma Biologics

Participants said comorbidities such as nasal polyps, atopy, eczema, and eosinophilic esophagitis often guide selection when several agents are appropriate, alongside dosing interval and patient preference. Several noted that insurer formularies increasingly determine which agent is started. At 1 participant's center, an internal prescribing algorithm and a monthly case conference guide decisions for patients who have cycled through multiple biologics.

Participants who use dupilumab frequently cited its use in steroid-dependent asthma, patients with elevated IgE, and its relative ease of approval. Another participant described avoiding dupilumab when eosinophil counts approach 1000 cells/µL or when patients have autoimmune or inflammatory conditions such as psoriatic arthritis or sarcoidosis, citing case reports of immune shifts.

Within the IL-5 class, some participants favored mepolizumab for its broad indications and the familiarity of its safety data, while others preferred benralizumab for more complete eosinophil depletion and every-8-week maintenance dosing. Participants who have prescribed depemokimab described using it for patients with severe eosinophilic asthma without major comorbidities who prefer twice-yearly dosing. Tezepelumab was described as an option for patients who do not meet biomarker thresholds for other agents, and mucus plugging data for both dupilumab and tezepelumab were reviewed, though most participants said plugging does not yet change their selection.

Eosinophilic COPD and Biologic Escalation

Khabbaza noted that an estimated 20% to 40% of patients with COPD have type 2 inflammation. In the BOREAS and NOTUS trials, dupilumab reduced exacerbations and improved prebronchodilator FEV1 in patients with eosinophil counts of 300 cells/µL or higher despite triple therapy, and in MATINEE, mepolizumab reduced exacerbations with a safety profile similar to placebo.2-4 Before escalation, participants emphasized confirming inhaler adherence and addressing other drivers, including noninvasive ventilation for hypercapnic respiratory failure and endobronchial valves for hyperinflation.

Some participants favored mepolizumab, citing its eligibility threshold of 150 cells/µL, while others favored dupilumab for patients with chronic bronchitis, counts above 300 cells/µL, or a priority on preserving FEV1. Khabbaza said dupilumab remains his first choice in COPD, though payer barriers have led him to start mepolizumab earlier in some patients. Participants described responses in COPD as more modest than in asthma, though 1 participant reported fewer hospitalizations after starting dupilumab and described both agents as well tolerated.

For unmet needs, participants cited earlier identification of frequent exacerbators, better inhaler education resources, and therapies for patients without type 2 inflammation.

"I think anything, less steroids, less hospital, and less symptoms are all going to be big victories," Khabbaza said.

References

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

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

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

4. Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181