EpistemisTezepelumab (Anti-TSLP)
Tezepelumab represents a conceptual advance in the biological therapy of bronchial asthma by proximally blocking the inflammatory signal in the respiratory epithelium (alarmins), before the cascade is differentiated into Th2 or non-Th2 phenotypes.
Mechanism
Mechanism of action
The respiratory epithelial barrier produces cytoprotective peptides and cytokines called alarmins in response to direct physical stimuli (pollutants, viruses, tobacco smoke, allergens). The main alarmin is Thymic Stromal Lymphopoietin (TSLP).
TSLP acts as a proximal alarm signaler that directly stimulates dendritic cells, ILC2 cells and local mast cells. This promotes the massive secretion of Th2 cytokines and the activation of non-eosinophilic inflammatory pathways associated with neutrophils.
Tezepelumab is a human IgG2λ monoclonal antibody that selectively binds to circulating TSLP, preventing its interaction with the complex of cellular TSLP heterodimeric receptors. By blocking the earliest epithelial signal, tezepelumab:
- Decreases the activation of adaptive and innate immune cells.
- Simultaneously reduces multiple systemic inflammatory biomarkers: blood eosinophils, total IgE and the fraction of exhaled nitric oxide (FeNO).
- Decreases bronchial hyperreactivity independently of the patient's basal inflammatory profile (Th2 or non-Th2).
Efficacy of Tezepelumab in Non-Eosinophilic Patients
Phase III clinical trials of tezepelumab (PATHFINDER and NAVIGATOR studies) demonstrated a significant 56% reduction in severe asthma exacerbations. Unlike biologics targeting IL-5 or IgE, tezepelumab demonstrated excellent efficacy in patients with low levels of blood eosinophils (< 150/µL) and low FeNO (< 20 ppb), a subgroup that previously lacked specific immunomodulatory treatment alternatives.
Pharmacokinetics
Pharmacokinetics
- Route of administration: Subcutaneous (SC).
- Absorption: Slow absorption; maximum serum concentration reached between 3 and 10 days after injection. Bioavailability of 77%.
- Metabolism: Systemic nonspecific proteolytic catabolism.
- Half-life: Approximately 26 days.
Indicators and dose
Dosage and Clinical Adjustment
Adults and adolescents 12 years old:
- 210 mg subcutaneously administered once every 4 weeks, via fixed-dose prefilled syringe for subcutaneous use. No adjustment for body weight or baseline IgE levels is required.
Organic adjustments: No dose adjustment is required in patients with renal or hepatic impairment.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Respiratory
- Cluster
- Third Generation Biologicals (Alarminas)