Predicting Biologic Response in Severe Asthma: Type 2 Inflammation and Phenotyping

Medical researchers have clarified the most effective methods for selecting biologic therapies for patients with severe asthma, emphasizing that while comprehensive patient profiles are helpful, the baseline level of type 2 inflammation is the most critical predictor of how a patient will respond to treatment.

In a correspondence published in The Lancet on April 4, 2026, authors responding to clinical commentary stated that blood eosinophils should not be used in isolation when determining the appropriate course of anti-cytokine biologic therapy.

Instead, the authors advocated for multicomponent phenotyping. This approach involves evaluating a combination of factors, including the patient’s age of onset, allergic status, specific biomarkers, and existing comorbidities, to better identify those most likely to benefit from these targeted treatments.

Despite the utility of these broader clinical profiles, the authors maintained that the strongest predictor of response remains the baseline level of type 2 inflammation.

The Role of Type 2 Inflammation and Biomarkers

Severe asthma is often driven by type 2 inflammation, a specific immune response that can be targeted with biologic agents. To identify this inflammation, clinicians rely on several validated biomarkers.

• Blood Eosinophils: High counts of these white blood cells are a key indicator. Evidence suggests that counts of 300 cells/μL or higher are a predictor of response to biologics.
• Fractional Exhaled Nitric Oxide (FeNO): This measure provides insights into airway inflammation. FeNO levels exceeding 40 ppb are associated with a higher likelihood of response to therapy.
• Serum IgE: Levels of immunoglobulin E are used to help guide the diagnosis and management of severe asthma.

These biomarkers help clinicians choose from a variety of biologic agents designed to block different parts of the inflammatory pathway. These include omalizumab, which targets IgE; mepolizumab and reslizumab, which target IL-5; benralizumab, which targets the IL-5 receptor alpha; dupilumab, which targets the IL-4 receptor alpha; and tezepelumab, which targets thymic stromal lymphopoietin.

Challenges in Clinical Management

While biologics have improved outcomes and made the goal of clinical remission possible, managing uncontrolled severe asthma remains complex. One significant challenge is that the very biomarkers used to guide treatment—such as FeNO, serum IgE, and blood eosinophils—can be suppressed by the biologic therapy itself.

the effectiveness of these treatments can be influenced by other factors. Research indicates that a lack of or low use of oral corticosteroids (OCS) is also a predictor of response to biologic therapy.

The objective of using these phenotype-driven and targeted approaches is to reduce the high economic burden and significant morbidity and mortality associated with severe asthma. By accurately identifying the underlying inflammatory driver, clinicians aim to prevent exacerbations and improve the overall health-related quality of life for patients who remain uncontrolled despite the use of maximal standard therapy, such as inhaled corticosteroids.

We agree that blood eosinophils should not be used in isolation and that multicomponent phenotyping—including age of onset, allergic status, biomarkers, and comorbidities—can help identify patients more likely to benefit from biologic therapy. However, the strongest predictor of response remains the baseline level of type 2 inflammation.

The Lancet, April 4, 2026