From the Guidelines
Tezepelumab (Tezspire) targets thymic stromal lymphopoietin (TSLP), while mepolizumab (Nucala) targets interleukin-5 (IL-5), representing a fundamental difference in their mechanisms of action for treating severe asthma. This distinction is crucial in understanding their efficacy and application in various asthma phenotypes. According to the most recent and highest quality study available 1, Tezspire works earlier in the inflammatory cascade by blocking TSLP, an epithelial cytokine that triggers multiple inflammatory pathways. This makes Tezspire effective across different asthma phenotypes, regardless of eosinophil levels or allergic status. In contrast, Nucala specifically targets IL-5, which primarily affects eosinophilic inflammation, making it most effective for patients with high blood eosinophil counts.
Key Differences and Implications
- Mechanism of Action: Tezspire targets TSLP, while Nucala targets IL-5, affecting different aspects of the inflammatory cascade in asthma.
- Efficacy Across Asthma Phenotypes: Tezspire's broader mechanism of action gives it potential advantages for patients who don't respond well to more targeted biologics like Nucala, especially those without clearly defined eosinophilic or allergic asthma.
- Administration and Patient Populations: Both medications are administered as injections but differ in their dosing schedules and approved patient populations, as noted in studies such as 1 and 1.
Clinical Considerations
- The choice between Tezspire and Nucala should be based on the patient's specific asthma phenotype, eosinophil levels, and response to previous treatments.
- Patient Selection: Patients with high blood eosinophil counts may benefit more from Nucala, while those with less defined eosinophilic or allergic asthma components might find Tezspire more effective.
- Dosing and Administration: Understanding the dosing schedules and potential for glucocorticoid sparing is crucial for managing patient expectations and optimizing treatment outcomes.
Given the most recent evidence 1, the decision to use Tezspire or Nucala should prioritize the patient's individual characteristics and asthma phenotype, considering the mechanisms of action and the potential benefits of each medication in improving morbidity, mortality, and quality of life.
From the Research
Target of Tezpire in Comparison to Nucala
- Tezpire (tezepelumab) targets thymic stromal lymphopoietin (TSLP), a cytokine involved in the initiation and persistence of airway inflammation in asthma 2, 3, 4, 5, 6.
- In comparison to Nucala (mepolizumab), which targets interleukin-5 (IL-5) and is used to treat severe asthma with an eosinophilic phenotype, Tezpire has a broader mechanism of action, blocking multiple inflammatory pathways, including IL-4, IL-13, and IL-5 3, 4.
- Tezpire's target, TSLP, is an upstream cytokine that orchestrates inflammatory responses in asthma, making it a promising target for treating severe uncontrolled asthma, regardless of phenotype or biomarker limitations 4, 5.
Mechanism of Action
- Tezepelumab binds to TSLP, inhibiting its interaction with the TSLP receptor complex, and preventing the activation of inflammatory cells 2, 4, 6.
- This mechanism of action leads to a reduction in serum total IgE levels, exhaled nitric oxide (FeNO), blood and sub-mucosal eosinophils, and bronchial hyperresponsiveness 3.
Clinical Implications
- Tezpire has shown safety and efficacy in clinical trials as an add-on therapy for patients with severe uncontrolled asthma, with a significant reduction in exacerbations and improvement in lung function and quality of life 3, 4, 5.
- The use of Tezpire may provide a new treatment option for patients with severe asthma who do not respond to existing therapies, including Nucala 5.