Advancements in Asthma Treatment: Tezepelumab's Role in Small Airways and Emerging Biologics

Asthma continues to pose significant challenges in treatment, yet the rise of biologics such as tezepelumab and rademikibart provides new hope. Current guidelines position biologics as add-on therapy for severe, uncontrolled asthma despite optimized inhaled treatment (for example, high-dose ICS/LABA), framing where these options fit in practice. These innovative therapies may enhance outcomes by reducing exacerbations and, in some cases, improving lung function.

Tezepelumab is emerging as an upstream anti-inflammatory therapy, with studies suggesting potential benefits in small airways function. Evidence to date reports observed reductions in peripheral resistance alongside fewer exacerbations, without establishing a specific small-airway targeting mechanism.

Trials demonstrate robust reductions in exacerbations across diverse phenotypes, with modest improvements in FEV1 and other lung function metrics. Recent research highlights these outcomes.

Targeting upstream pathways may support longer-term control, though confirmation requires longitudinal follow-up. Early reports suggest rademikibart could reduce exacerbations in eosinophilic asthma; peer-reviewed data are awaited.

Results from tezepelumab trials signal a broader shift in severe asthma management. Meanwhile, emerging agents such as rademikibart are under evaluation. Understanding asthma endotypes and biomarkers underpins therapy selection—a foundation of personalized care, as discussed in this review.

Such findings are reshaping how clinicians approach severe, uncontrolled asthma despite high-dose ICS/LABA. Focusing on mechanisms that reduce airway resistance offers a path when standard inhaled regimens (for example, ICS/LABA ± LAMA) fall short. Managing small airways dysfunction remains complex in this context.

Given tezepelumab's trial-demonstrated reduction in exacerbations and the structure provided by endotype phenotyping, the next logical step is to integrate biologics within stepwise management frameworks. Within stepwise frameworks, biologics are considered add-on therapy for severe asthma at higher steps of care (Step 5/6), with selection guided by phenotype and biomarkers such as blood eosinophils and FeNO. The focus on precision medicine is increasing, paving the way for therapies that align closely with individual patient profiles and needs.

Key Takeaways:

• Tezepelumab shows robust reductions in exacerbations across phenotypes, with modest gains in lung function.
• Biologics are add-on options for severe asthma within stepwise care, with selection guided by phenotype and biomarkers.
• New candidates like rademikibart remain investigational, with early signals in eosinophilic disease pending peer-reviewed confirmation.