Beyond Step-Up Therapy: Biologic Initiation, Selection, and Access in Asthma and COPD

The biologic treatment landscape for severe asthma and chronic obstructive pulmonary disease (COPD) continues to expand, with 7 approved biologics now available for asthma and 2 for eosinophilic COPD, yet real-world integration has remained uneven across practice settings and patient populations. Short-acting beta-agonist (SABA) overuse — defined as ≥3 canisters per year — is now recognized as a marker of inadequate disease control and is independently associated with increased exacerbation risk and all-cause mortality, yet it remains systematically undercaptured in clinical practice.¹

Oral corticosteroid (OCS) burden represents a parallel and equally undermonitored problem: large cohort analyses have demonstrated dose-response relationships between cumulative OCS exposure and serious adverse outcomes — including type 2 diabetes, osteoporosis, and cardiovascular events — beginning at cumulative prednisolone-equivalent doses as low as 500 mg, a threshold easily reached within 1 to 2 acute exacerbation courses per year.²

Recently, the LIBERTY ASTHMA VENTURE trial established that dupilumab enables meaningful and durable OCS reduction in steroid-dependent severe asthma, with approximately 80% of treated patients achieving clinically significant OCS tapering — including concurrent FEV1 improvement of approximately 220 mL despite reduced corticosteroid exposure.³ In COPD, dupilumab and mepolizumab are now endorsed by GOLD 2026 as add-on options for patients with eosinophilic disease and ongoing exacerbations despite triple inhaled therapy, based on the BOREAS, NOTUS, and MATINEE trial programs.⁴˒⁵˒⁶

Against this backdrop, HCPLive convened a virtual clinical forum in May 2026 moderated by Jacqueline B. Sutter, DO, a pulmonologist and critical care physician in the greater Philadelphia area that included pulmonologists from a variety of backgrounds of care. This practice-setting heterogeneity distinguished the discussion from predominantly specialist-to-specialist forums and grounded the conversation in the referral dynamics, access barriers, and patient health literacy challenges that shape biologic use in the real world.

The forum convened as the NIMBLE trial — confirming non-inferiority of switching from mepolizumab or benralizumab to depemokimab — had recently been published, and as CT-based mucus plug scoring data from the VESTIGE and CASCADE trials were generating active discussion about whether imaging biomarkers might eventually supplement eosinophils and FeNO in guiding biologic selection in asthma.⁷˒⁸˒⁹ Both conversations came up directly in the forum's discussion, as did renewed attention to the SABINA program's data on SABA overuse as a more reliable, real-time marker of disease burden than patient self-report.¹ In COPD, GOLD 2026's formal endorsement of biologic escalation — alongside a strengthened recommendation for baseline CT in all patients — represented a framework the group applied cautiously, acknowledging that the patient selection algorithm that practitioners need most is still in development.

The asthma portion of the forum was shaped by the heterogeneity of the panel. A family physician described a referral threshold after step-up ICS and LTRA failure, familiarity with dupilumab and omalizumab by brand name, and reliance on specialists for final agent selection — a common pattern in primary care that the moderator acknowledged as appropriate but also noted creates significant workflow burden on pulmonology and allergy practices that absorb these referrals. Panelists described checking blood eosinophils, IgE, and allergen panels on most new asthma patients and using FeNO both for initial phenotyping and longitudinal monitoring; practice access to FeNO varied, with NIH and academic clinic sites using it routinely and community practices less consistently. OCS tracking emerged as a particular focus: panelists described the practical challenge of calculating cumulative exposure across fragmented care systems and proposed EMR-based cumulative OCS calculators as a high-priority workflow improvement. The VENTURE trial's OCS-sparing and FEV1 improvement data was highlighted by Sutter as among the most clinically compelling arguments for dupilumab in steroid-dependent patients who may not have reliable eosinophil counts. Depemokimab's twice-yearly dosing drew split opinion — viewed as appealing by adherence-challenged or travel-limited patients, and with some caution by Sutter regarding the challenge of recognizing suboptimal control across a 6-month interval. The mucus plug data from VESTIGE and CASCADE was broadly acknowledged as mechanistically explanatory but not yet practice-changing, with one panelist noting that IL-13's role in mucus hypersecretion is well established and the imaging data reinforces rather than redefines that understanding.

“As a fairly young graduate who kind of was trained in the era of biologics. I would say I probably became more, I don't want to say aggressive, but I definitely became more mindful of maybe considering earlier transitions to biologics,” a panelist said.

The COPD discussion centered on the persistent challenge of patient selection and the slower pace of biologic adoption relative to asthma. Panelists described the inpatient exacerbation as the most reliable clinical trigger for eosinophil measurement in COPD, acknowledging that by that point patients have typically already received systemic steroids, suppressing the count. A substantive conceptual discussion about whether "eosinophilic COPD" represents a distinct phenotype or simply ACOS relabeled — prompted by the most experienced panelist, with 32 years in practice — reflected a real divide in clinical thinking that the moderator framed pragmatically: if T2 inflammation is present, treat it regardless of diagnostic label. Polling results from the COPD segment were consistent with every prior forum in this HCPLive series: payer support and reimbursement guidance, followed by clearer patient selection algorithms, were the factors practitioners most needed. Panelists closed with cautious optimism noting that a generation trained in the era of biologics is now entering independent practice with more structured prescribing frameworks for asthma than for COPD, and expressing that the COPD side of this field is most in need of the kind of phenotypic clarity that eos and FeNO eventually provided in asthma.

References

1. Larsson K, Stallberg B, Lisspers K, et al. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020;55(4):1901872. doi:10.1183/13993003.01872-2019

2. Loftus PA, Wise SK. Cumulative oral corticosteroid exposure in asthma and morbidity: a dose-response relationship. ERJ Open Res. [Danish cohort reference]: Ekberg-Aronsson M et al. Confirmed reference: Søndergaard MB, Hilberg O, Davidsen JR, et al. Low-dose oral corticosteroids in asthma associates with increased morbidity and mortality. Eur Respir J. 2022;60(2):2102229. doi:10.1183/13993003.02229-2021.