Tezepelumab therapy cessation leads to a gradual increase in biomarkers and clinical outcomes, suggesting a potential disease-modifying effect.

After tezepelumab therapy is stopped, biomarkers and clinical outcomes slowly decrease over 40 weeks but do not return to baseline. This hints at a disease-modifying effect of tezepelumab, in at least a subset of patients.

Tezepelumab is a human monoclonal antibody that prevents thymic stromal lymphopoietin (TSLP) from interacting with its heterodimeric receptor. TSLP is involved in the inflammatory cascades of all asthma phenotypes and therefore offers the option of broadly influencing asthma pathophysiology. As Christopher Brightling, PhD, pointed out at the 2023 ERS International Congress, tezepelumab is approved for the treatment of severe bronchial asthma as a consequence of the positive results of the phase 3 NAVIGATOR and SOURCE trials.

Following these phase 3 trials, patients had the opportunity to participate in the extension study DESTINATION, a phase 3, multicenter, randomized, placebo-controlled trial. Long-term treatment with tezepelumab in DESTINATION resulted in fewer exacerbations, improvement in lung function and symptom control, and reduced inflammatory biomarkers over 104 weeks. As Dr. Brightling explained, with their current study they want to explore the effect of tezepelumab cessation after 2 years of treatment. All participants had taken part in the NAVIGATOR trial and in the DESTINATION long-term extension period and had received the last tezepelumab dose at week 100. From that time on, biomarkers and clinical outputs were assessed in the 40-week period after the last dose. Change over time was assessed in blood eosinophil count (BEC), fractional exhaled NO (FeNO), the Asthma Control Questionnaire (ACQ)-6 score, and FEV₁ before bronchodilation (pre-BD ppFEV₁).

Both biomarkers gradually increased from week 4 after the last dose of tezepelumab. Similarly, pre-BD FEV₁ gradually decreased from week 4 after the last dose of tezepelumab. Moreover, ACQ-6 scores gradually increased from this time on. However, Dr. Brightling emphasized that although biomarker suppression and improved clinical outcomes gradually waned in the 40 weeks after cessation of the biologic, these parameters did not return to baseline. Therefore, further studies should explore which patient subgroups may achieve sustained asthma control to assess a potential disease-modifying effect of tezepelumab in some patients.

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