Clinical Forum Insights: When to Escalate to Biologics in Asthma and COPD?

The biologic landscape for obstructive airway disease has expanded on 2 fronts, with a twice-yearly anti-interleukin (IL)-5 agent now available for severe asthma and 2 biologics approved for chronic obstructive pulmonary disease (COPD) with eosinophilic inflammation.1-4 Biomarker thresholds, payer criteria, and patient preferences now shape which patients reach these therapies and when. Decisions about escalation timing and agent selection increasingly fall to clinicians in practice.

In September 2026, Christopher L. Mosher, MD, MHS, assistant professor of medicine at Duke University, moderated a virtual clinical forum on targeted therapy in asthma and COPD. Participants included pulmonary and critical care physicians from Duke and the Durham VA, a private practice pulmonologist from South Carolina, and a critical care nurse practitioner from Virginia. The discussion covered type 2 biomarkers, thresholds for biologic initiation, agent selection, and unmet needs in COPD.

Type 2 Biomarkers and Biologic Thresholds in Severe Asthma

Mosher reviewed Global Initiative for Asthma thresholds for blood eosinophil counts and fractional exhaled nitric oxide (FeNO), noting that oral corticosteroids (OCS) lower eosinophil counts and current smoking lowers FeNO. Participants described using FeNO to question the diagnosis when it is undetectable in patients not on maintenance corticosteroids, and as a longitudinal marker when stepping therapy up or down. A private practice participant said unpredictable reimbursement limits FeNO use outside research settings, and VA-based participants noted it is not available at every site.

Participants generally described 2 or more OCS bursts in a year despite high-dose inhaled therapy as their threshold for considering a biologic, and 1 VA-based participant said they may discount a single burst tied to a viral infection. Several stressed reviewing outside records, describing patients who received steroid courses from urgent care, other health systems, or virtual rehabilitation providers without documentation in their own charts. Participants also emphasized confirming the diagnosis, checking inhaler technique, and addressing environmental triggers and smoking before escalation.

Selecting Among Asthma Biologics

Participants said biomarkers guide selection most often, followed by comorbidities such as chronic rhinosinusitis with nasal polyps, atopy, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis. In the approach described by 1 participant, steroid dependence is the first branch point, followed by comorbidities, biomarkers, and aversion to injections. That participant said very high peripheral eosinophilia may favor an anti-IL-5 agent over dupilumab given the potential for treatment-emergent eosinophilia, and that tezepelumab remains an option for both low and mixed type 2 phenotypes.

Participants who prescribe dupilumab described checking eosinophil counts at about 3 months, particularly when baseline counts are elevated. According to 1 participant, dupilumab was stopped once after counts rose to approximately 2000 cells/µL, while another described monitoring asymptomatic patients with higher counts without stopping therapy.

Mosher reviewed extension data showing sustained exacerbation reductions with dupilumab, mepolizumab, benralizumab, and tezepelumab over 2 to 4 years, along with SWIFT-1 and SWIFT-2 data for twice-yearly depemokimab.1 Some participants said they reserve depemokimab for patients already responding to an anti-IL-5 agent who want fewer injections, rather than starting it in biologic-naive patients. Mucus plugging data for dupilumab and tezepelumab were also reviewed, though participants said mucus plug scoring has not entered routine practice because no clinical quantification tool is available and computed tomography is not routinely obtained for that purpose.

Eosinophilic COPD and Biologic Escalation

Participants described checking eosinophil counts routinely in COPD, including at the time of exacerbation before systemic steroids are given when possible. In the BOREAS and NOTUS trials, dupilumab reduced moderate or severe exacerbations in patients with eosinophil counts of 300 cells/µL or higher, with rate ratios of 0.70 and 0.66, respectively, and improved lung function in both trials and quality of life in BOREAS.2,3 In the MATINEE trial, mepolizumab reduced the annualized rate of moderate or severe exacerbations by 21% in patients with counts of 300 cells/µL or higher, without significant improvements in quality of life or lung function.4

Mosher noted that the mepolizumab label permits use at lower eosinophil thresholds than those required in MATINEE. Of the participants who addressed agent choice, 2 said the breadth of the dupilumab data, including its secondary end points, makes it their first choice for eosinophilic COPD, and 1 described hesitancy using mepolizumab in patients with counts between 150 and 300 cells/µL. Another participant described trialing de-escalation of inhaled corticosteroids in patients on triple therapy with recurrent pneumonia before turning to a biologic.

Participants noted that most patients with COPD do not have type 2 inflammation, and 1 participant called for head-to-head comparisons of ensifentrine, roflumilast, and azithromycin for patients who do not meet biologic criteria.

“Having a biologic that's going to target the Th2-low population, I think, would really be a significant advancement for the field," Mosher 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