Clinical and Biological Remission With Tezepelumab: The Real-World Response in Severe Uncontrolled Asthma

Introduction

Tezepelumab is an anti-TSLP monoclonal antibody approved for the treatment of severe asthma. It has broad downstream anti-T2 effects, offering the prospect of biological remission. Real-world data on clinical remission rates with tezepelumab is lacking, and the relationship between clinical and biological remission is unclear. Finally, the effectiveness of tezepelumab in patients who have failed to respond to existing biologic therapies is unknown.

Methods

Clinical and biomarker data from adults with severe asthma treated with tezepelumab in a real-world setting was analyzed. Clinical outcome measures including clinical remission were recorded along with rates of biological remission (defined as blood eosinophil count < 300 cells/mcL and FeNO < 25 ppb).

Results

One hundred seventy-five patients were included. 98/175 (56%) had switched from another biologic. Following tezepelumab initiation, the exacerbation rate decreased from 3.1 (2.5) to 0.8 (1.4), with 59% of patients remaining exacerbation-free at 1 year. 54% achieved an ACQ score < 1.5. Clinical remission at 1 year was observed in 36%, with a rate of 55% in T2-high patients versus 19% in T2 low patients. The clinical response in biologic-naïve and biologic switch patients was similar. FeNO declined from 41 ppb (24–76) to 24 ppb (16–38) and BEC fell from 300 cells/μL (60–610) to 180 cells/μL (105–320) (both p < 0.001). 38% achieved biological remission. 15% attained both clinical and biological remission.

Conclusion

Tezepelumab led to substantial clinical improvements and clinical remission in up to 55% of T2-high patients with severe asthma. A disconnect between clinical and biological remission was observed. The long-term significance of residual T2 inflammation on tezepelumab is unknown.