Biologic Therapies Transform Respiratory Care as Clinicians Embrace Earlier, Precision-Based Treatment Strategies
核心洞察
Biologic therapies including dupilumab, benralizumab, and tezepelumab have revolutionized asthma management by enabling biomarker-driven treatment strategies beyond traditional allergen or eosinophil-based models.
Dupilumab's 2024 FDA approval for eosinophilic COPD represents the first biologic therapy for this condition, marking a significant milestone in a field where treatment had previously stagnated.
Clinicians are increasingly adopting earlier biologic intervention strategies to minimize steroid exposure and prevent long-term adverse outcomes, with pulmonologists now managing biologics more independently.
The landscape of respiratory medicine has undergone a dramatic transformation over the past decade, driven by advances in understanding asthma and chronic obstructive pulmonary disease (COPD) pathophysiology and the emergence of targeted biologic therapies. Where treatment once centered largely on inhaled corticosteroids and bronchodilators, the field has entered a new era defined by phenotypic precision, biomarker-driven strategies, and earlier, more tailored intervention.
Revolutionary Biologics Reshape Asthma Treatment
In asthma care, the approvals of biologics like dupilumab (Dupixent), benralizumab (Fasenra), and most recently tezepelumab (Tezspire) have allowed treatment to move beyond allergen or eosinophil-based models toward broader and more inclusive criteria. Tezepelumab's 2021 FDA approval marked a turning point as the first biologic approved for severe asthma regardless of baseline eosinophil count.
These developments have redefined what "uncontrolled" asthma means and raised the bar for treatment goals—including reduced exacerbation rates, improved lung function, and steroid-sparing potential. As a result, allergists and pulmonologists are increasingly aligned in a shared, multidisciplinary approach to asthma management, focused on identifying the right therapy for the right patient as early as possible.
"If you pick the right biomarker, it's not just a number. It's actually a target and something that you can follow over time to ascertain if the disease state is improving," said Dr. Lorraine Anderson, allergist-immunologist at UCLA. "We now know that asthma is heterogeneous. You see a lot of patients with shortness of breath, chest tightness, wheezing, and cough. If you zoom in, they do not have the same inflammatory state, and if you're able to find a biomarker to hone in on which kind of inflammation is going on, you can just identify that patient and find a target."
COPD Enters the Biologic Era
COPD, historically considered less amenable to targeted therapy, has begun to follow a similar trajectory. In 2024, dupilumab became the first biologic approved for eosinophilic COPD in the US, signaling new therapeutic possibilities in a field where treatment had long stagnated. At the same time, a growing understanding of COPD endotypes and inflammatory mechanisms is prompting a reevaluation of how the disease is diagnosed and managed.
The recognition that COPD is even more heterogeneous than asthma has led to the identification of a significant subset of patients with eosinophilic inflammation who benefit from therapies traditionally used in asthma. Dupilumab and mepolizumab both show efficacy in patients with ≥300 eosinophils/μL, though their relative positioning and long-term roles are still being debated.
"Asthma is in young population. COPD is usually in the older population. So that's a big difference in terms of inflammation. They're far gone. So, then you feel the rush to reverse, which sometimes is not reversible. Asthma, you want to prevent chronic steroid use because they're in a young age. So, I think inflammation is very different in the 2 diseases," participants noted during clinical discussions.
Shift Toward Earlier Intervention
A significant trend emerging in clinical practice is the move toward earlier biologic initiation to reduce cumulative steroid burden and prevent long-term adverse outcomes. Pulmonologists are increasingly managing biologics directly, with less reliance on allergists, as familiarity and comfort with these therapies increase.
"I've been more aggressive with, if my patient needs steroids more than twice in 6 months or so, I'm pulling the trigger faster and faster, even without long-acting muscarinic antagonist (LAMA), just because I first-hand know the major long-term side effects of steroids 10 years, 15 years down the road," one participant explained. "I'm not going to try and let anybody go through that. And I've been very quick with pulling the triggers on biologics in that sense."
Biomarker-Driven Precision Medicine
The evolution toward personalized medicine has been supported by advances in biomarker understanding and application. Biomarkers such as eosinophils, IgE (搜索), and FENO (搜索) have become essential, though imperfect, tools for guiding therapy. Type 2 inflammation, especially eosinophilic, has emerged as the most actionable phenotype for biologic intervention in both asthma and COPD.
However, biomarker development remains challenging in COPD, with limited predictive reliability and interference from factors like smoking. The field continues to work toward better phenotyping and broader definitions of eligibility, particularly in the COPD population.
Expanding Therapeutic Horizons
Clinical experts are also exploring the potential of biologics in related conditions such as bronchiectasis and asthma-COPD overlap. "We're seeing more bronchiectasis because it's being identified. These people were being labeled as chronic bronchitis before COPD," participants noted. "It's a hot topic right now because we're going to finally have a targeted drug specifically for bronchiectasis."
The boundaries between asthma and COPD continue to blur as clinicians recognize overlapping inflammatory pathways and treatment responses. This has led to greater overlap in how clinicians think about asthma and COPD care and presents new challenges in integrating advanced therapeutics into real-world workflows.
Future Outlook
As Dr. Joseph Khabbaza of Cleveland Clinic summarized, "Asthma and COPD have evolved over the last few years and with a lot of thinking about eosinophils and type 2 inflammation, and we now have more pathways and more treatments than ever before to try to help these patients. And we want to minimize prednisone, and minimize exacerbation. I think those are- If we can do those two things in asthma and COPD patients, that'll be good for everyone in the system."
The field continues to advance with increasing interest in personalized combinations, longer-acting biologics, and early biologic use in difficult-to-treat respiratory conditions. While current trial designs have limitations and gaps exist between real-world patients and study populations, the emphasis on biologics and personalized medicine, especially biomarker-guided approaches, continues to grow across respiratory conditions.