Tezepelumab decreases matrix remodelling and inflammatory pathways in patients with asthma

Background: Tezepelumab, a human monoclonal antibody that selectively blocks thymic stromal lymphopoietin interaction (TSLP) with its receptor, improved clinical outcomes vs. placebo in patients with severe, uncontrolled asthma (Phase 2b PATHWAY study [NCT02054130]). Proteomics analysis was performed to further elucidate mechanisms of tezepelumab activity in patients with asthma. Aim: To determine which serum proteins are altered by tezepelumab. Methods: Patients were randomised to tezepelumab-treatment arms or placebo (Corren et al. NEJM 2017;377:936–46). Serum protein levels were assessed at baseline and at multiple post-treatment timepoints up to Week 52 using the Myriad Rules Based Medicine (RBM) and SomaLogic platforms (122 and 1305 analytes, respectively). Significant changes were determined by ANOVA and t-tests at each timepoint, with percent changes from baseline also being assessed. We also explored associations between baseline levels of RBM proteins and clinical biomarkers. Results: Levels of matrix remodelling (MMP-10, periostin), eosinophil-related (IL5RA, PAPP‑A), IgE and TARC proteins decreased significantly post-treatment (>10% change in tezepelumab vs. placebo at Week 52, p Conclusions: Tezepelumab led to a decrease in biomarkers of inflammation and matrix remodelling, which were correlated with bEOS and FENO levels at baseline. Modulation of matrix remodelling proteins may reflect a novel mechanism of action for tezepelumab in addition to the inhibition of airway inflammation. Co-sponsored by MedImmune, a member of the AstraZeneca Group, and Amgen Inc.