Biomarkers, Biologics, and Beyond: Managing Severe Asthma in the Real World

Over the past decade, the treatment paradigm for severe asthma has been reshaped by the approval of targeted biologics and a deeper understanding of inflammatory pathways driving disease. What began with agents like omalizumab has rapidly expanded with the approvals of mepolizumab, benralizumab, and dupilumab—and most recently, tezepelumab in 2021, which became the first biologic approved for severe asthma regardless of baseline eosinophil count. These therapies have set a new standard of care for type 2–high asthma and are prompting earlier identification of eligible patients, more nuanced treatment algorithms, and greater emphasis on biomarker-driven decisions.1 More recently, the 2024 approval of dupilumab for eosinophilic chronic obstructive pulmonary disease (COPD) has opened new doors for targeted therapy in a population that long lagged behind asthma in biologic innovation.2

With each new approval, the expectations for disease control and long-term outcomes continue to evolve, ushering in a new era where earlier diagnosis, individualized therapy selection, and consistent biomarker assessment are becoming essential components of care. Clinicians are now tasked not just with managing symptoms, but with navigating a growing array of therapeutic options, understanding nuanced eligibility criteria, and integrating these treatments into increasingly complex clinical workflows. The potential for long-term steroid-sparing, exacerbation reduction, and quality-of-life improvements is greater than ever—but so too is the need for clear guidance on optimizing these innovations in practice.

At a recent clinical forum convened by HCPLive in Houston, Texas, a group of pulmonologists, led by Nicola A. Hanania, MD, MS, Associate Professor of Medicine at Baylor College of Medicine Airways Clinical Research Center, gathered to examine how these developments are playing out in practice.

Their discussion focused on the practicalities of initiating and sequencing biologics, the value and limitations of biomarkers like eosinophils and FeNO, and the need for more structured approaches to early referral and diagnosis. They discussed how the last 2 decades of asthma research have shifted clinical paradigms toward targeted, phenotype-driven biologic therapies.

"The biggest thing that I think is missed in all these discussions are that the steroid inhalers are still the key and making sure they're taking it correctly. And taking regularly Because the compliance on the steroid inhaler is still the biggest problem. They get better, they stop using it," one panelist pointed out.

Type 2 inflammation remains a central focus, with discussion on how eosinophils, FeNO, and IgE levels guide patient selection and biologic choice, although real-world use is hampered by access, education, and insurance hurdles. These barriers highlight how real-world implementation is now the critical frontier in maximizing biologic impact. They also emphasized the critical role of multidisciplinary collaboration in delivering personalized asthma care.

"The big issue is, should we phenotype everybody with asthma? Probably not. But the ones that we see as specialists are the ones that are problematic. I think primary care, we are trying to build bridges with primary care for them at least to look at the blood eosinophils, to think about deferring patients with high risk of exacerbation," Hanania said.

Panel participants shared insights on challenges in diagnosis, treatment adherence, inhaler technique, and navigating insurance for biologics, underscoring the complexity of treating severe asthma in both public and private settings. They outlined how shared decision-making, comorbidity considerations, and patient convenience shape treatment plans.

Looking at the long-term impact of biologics on the asthma field, they reiterated that real-world evidence supports sustained biologic efficacy, while questions do remain about tapering, biomarker monitoring, and the possibility of treatment discontinuation in clinical remission. The group also touched on emerging needs in COPD and non-type 2 asthma, as well as the potential for dual-target or multi-mechanism therapies in the future.

"I think every single biologic out there has to be experimented with. I'd really love to see if we can expand the use of what's out there that people can do and make it even a little more accessible for patients," one panelist concluded.

REFERENCES

1. FDA Approves Tezspire™ (Tezepelumab-ekko) in the U.S. for Severe Asthma. News release. Amgen. December 17, 2021. https://www.amgen.com/newsroom/press-releases/2021/12/fda-approves-tezspire-tezepelumabekko-in-the-us-for-severe-asthma

2. Dupixent® (dupilumab) Approved in the U.S. as the First-ever Biologic Medicine for Patients with COPD. Regeneron Pharmaceuticals, Inc. September 27, 2024. https://www.globenewswire.com/news-release/2024/09/27/2954552/0/en/Dupixent-dupilumab-Approved-in-the-U-S-as-the-First-ever-Biologic-Medicine-for-Patients-with-COPD.html.