Beyond biomarkers: the role of clinical factors associated with biologic therapy response in severe asthma

Ann Med. 2026 Dec;58(1):2627026. doi: 10.1080/07853890.2026.2627026. Epub 2026 Feb 11.

Abstract

Background: Severe asthma carries a high burden and often requires biologic therapy targeting type 2 (T2) inflammation. However, treatment response is heterogeneous, and traditional biomarkers, such as blood eosinophils, fractional exhaled nitric oxide (FeNO), and total serum IgE, may not fully explain this variability .

Objective: To evaluate clinical and inflammatory characteristics associated with response to biologic therapies in a real-world cohort of severe asthma patients.

Methods: A single-center, ambispective observational study was conducted in the Allergology Department of A Coruña, Spain. Sixty-seven patients with severe uncontrolled asthma and treated with omalizumab, mepolizumab, benralizumab, dupilumab, or tezepelumab, were included. Patients were followed for ≥12 months. Clinical variables and inflammatory biomarkers were assessed at baseline, 4-6 months, and 12 months. Comparisons between biologic subgroups and logistic regression analyses were performed to identify factors associated with response.

Results: Female sex, nasal polyposis, elevated blood eosinophils, and frequent exacerbations were associated with better response to biologics. Clinical factors such as nasal polyposis and aspirin-exacerbated respiratory disease (AERD) showed a stronger association with treatment response than standard biomarkers (FeNO, blood eosinophils). The mean diagnostic delay was 12.1 years, suggesting a potential influence on therapeutic results.

Conclusion: Beyond traditional biomarkers, clinical factors particulary nasal polyposis and AERD may play a key role in understanding response patterns to biologics. Incorporating these variables into clinical assessment may help support a more personalized management approach in severe asthma.

Keywords: Aspirin-induced asthma (aspirin-exacerbated respiratory disease – AERD); biological therapy; biomarkers; clinical factors; eosinophilia; nasal polyps; precision medicine; severe asthma.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Anti-Asthmatic Agents* / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Asthma* / blood
  • Asthma* / drug therapy
  • Asthma* / immunology
  • Biological Therapy* / methods
  • Biomarkers / blood
  • Eosinophils
  • Female
  • Fractional Exhaled Nitric Oxide Testing
  • Humans
  • Immunoglobulin E / blood
  • Male
  • Middle Aged
  • Nasal Polyps
  • Omalizumab / therapeutic use
  • Severity of Illness Index
  • Spain
  • Treatment Outcome

Substances

  • Biomarkers
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin E
  • mepolizumab
  • Omalizumab
  • benralizumab