SEVERE ASTHMA is a complex and burdensome condition, often resistant to conventional therapies. Biologics targeting type 2 (T2) inflammation have transformed treatment, improving symptoms and reducing exacerbations. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), offers broader T2 suppression and is unique in being licensed for use regardless of T2 biomarker levels.
A recent real-world study at Guy’s Severe Asthma Centre, London, explored the effectiveness of tezepelumab in a large, diverse cohort of adults with uncontrolled severe asthma. Notably, the analysis included both biologic-naïve patients and those who had failed previous therapies targeting IL-5 or IL-5R.
The researchers found that most patients showed substantial improvements across all major clinical outcomes. Nearly 60% met at least three out of four clinical remission criteria, and over one-third achieved full clinical remission. Importantly, those with higher baseline T2 biomarkers had the best outcomes, 55% of these patients achieved remission, compared to just 18% in the T2-low group.
Interestingly, the study also revealed a disconnect between clinical and biological remission. Many patients who met clinical remission criteria still had elevated biomarkers like blood eosinophils and FeNO. Conversely, some patients with suppressed T2 inflammation failed to achieve clinical remission, suggesting persistent symptoms may stem from non-T2 pathways or comorbid conditions.
Tezepelumab also showed promise in patients previously unresponsive to other biologics. These individuals, often with high FeNO but poor response to IL-5 inhibitors, demonstrated notable clinical improvements, supporting the value of targeting upstream cytokines like TSLP.
Despite these encouraging results, unresolved questions remain, particularly regarding the long-term implications of residual T2 inflammation and the lack of effective options for genuinely T2-low patients. Overall, this study confirms the real-world effectiveness of tezepelumab, while highlighting the need for further research into individualised approaches and broader biologic targets in severe asthma.
Reference
Gates J et al. Clinical and biological remission with tezepelumab: the real-world response in severe uncontrolled asthma. Allergy. 2025;DOI:10.1111/all.16590.
