Tezepelumab: A Transformative Approach in Severe Asthma Management

In the rapidly advancing world of asthma treatment, tezepelumab stands out as an important addition for severe cases. It is FDA-approved as add-on maintenance for severe asthma, and guidelines position it as an option after high-dose ICS/LABA in patients with ongoing exacerbations, regardless of eosinophil count.

The role of tezepelumab in asthma management is gaining recognition, representing a significant advancement by blocking the upstream epithelial cytokine TSLP, influencing multiple downstream pathways (T2 and some non–T2).

This approach supports improved symptom control and fewer exacerbations.

Upstream TSLP inhibition can dampen T2-high and some non–T2 inflammation, which is associated with fewer exacerbations. Disrupting these pathways has proven implications, addressing symptoms and minimizing steroid dependence, which enhances patient outcomes.

In OCS-dependent severe asthma cohorts, tezepelumab has shown potential to reduce maintenance steroid doses in clinical studies. The WAYFINDER summary highlighted OCS-sparing themes but should be interpreted alongside primary trial data.

Pivotal trials report fewer exacerbations, and in OCS-dependent cohorts some patients reduced maintenance steroid doses; emerging real-world reports mirror these patterns. Together, these trial and observational reports support tezepelumab’s role without implying it constitutes a new tier of therapy.

For patients experiencing frequent exacerbations, improvements may reflect effective upstream targeting, though responses vary by phenotype and prior exacerbation history. Reduced steroid dependence translates directly to a higher quality of life, illustrating promising shifts in long-term management.

Managing steroid side effects remains a central concern, particularly when patients have limited alternative therapies. Despite advances in biologics, full access remains challenging for many patients due to cost, prior authorization, and step-therapy or biomarker criteria imposed by payers.

Because tezepelumab blocks the upstream cytokine TSLP, some eligible patients may reduce OCS needs. This provides broader implications for personalized care and highlights the pathway to more tailored treatment plans.

Next steps include broader adoption in clinics, more head-to-head and long-term studies, and clearer patient education materials.

Key Takeaways:

• TSLP-targeting mechanism may confer efficacy across eosinophil levels.
• Evidence shows fewer exacerbations and potential OCS-sparing in studied populations.
• Positioned after high-dose ICS/LABA for severe asthma in guidelines and FDA labeling.