Mechanisms and Treatment of Type 2 High and Low Asthma Endotypes

Clin Exp Allergy. 2025 Sep;55(9):773-783. doi: 10.1111/cea.70084. Epub 2025 Jun 3.

Abstract

Asthma is a complex, heterogeneous disease characterised by clinical phenotypes demonstrating distinct and overlapping immunological mechanisms, classified into type-2 high and type-2 low asthma endotypes. Both allergic and eosinophilic non-allergic asthma are driven through an underlying type-2 high-endotype, which can be targeted using therapeutic approaches such as allergen-specific immunotherapy (AIT) for allergic asthma and biologics. AIT demonstrates efficacy for the treatment of allergic asthma. Approved biologics for asthma management include using various interleukin antagonists and anti-immunoglobulin E, with Tezepelumab offering promising treatments for both type-2 high and type-2 low asthma patients. Novel therapeutic candidates, such as Itepekimab and depemokimab, have demonstrated promising results in a Phase 2 clinical trial in moderate-to-severe asthma patients.

Keywords: allergen‐specific immunotherapy; asthma; biologics; biomarkers; endotype; phenotype.

Publication types

  • Review

MeSH terms

  • Anti-Asthmatic Agents* / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Asthma* / diagnosis
  • Asthma* / etiology
  • Asthma* / immunology
  • Asthma* / therapy
  • Desensitization, Immunologic* / methods
  • Humans
  • Phenotype

Substances

  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized