Functional Molecular Network Analysis Enables Prediction of Response to Vedolizumab Therapy in Anti-TNF Refractory IBD Patients

Author:

Breidert Matthias1,Eftekhari Pierre2,Louis François2,Rotoiu Claudia1,Rath Timo34,Neurath Markus F34,Atreya Raja345

Affiliation:

1. Department of Gastroenterology and Hepatology, City Hospital Waid and Triemli, Zürich, Switzerland

2. Inoviem Scientific, BIOPARC 3, Illkirch-Graffenstaden, France

3. Department of Medicine I, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

4. Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany

5. The Transregio 241 IBDome Consortium

Abstract

Abstract Background We applied for the first time 2 label-free technologies, physiological intermolecular modulation spectroscopy (PIMS) and nematic protein organization technic (NPOT) in anti-tumor necrosis factor (TNF) refractory inflammatory bowel disease (IBD) patients to identify clinical responders to vedolizumab therapy and elucidate their underlying functional molecular network. Methods PIMS analysis was performed in peripheral blood taken prior to the first vedolizumab application in 20 IBD patients (Crohn disease n = 13; ulcerative colitis n = 7) refractory to at least 1 previous anti-TNF agent therapy. Peripheral blood taken from clinical responders and nonresponders at week 14 of vedolizumab therapy were additionally subjected to NPOT analysis. Response to therapy was assessed by respective clinical disease activity scores (partial Mayo Score and Harvey–Bradshaw Index). Results Clinical response to vedolizumab treatment was observed in 7 of 13 Crohn disease and 4 of 7 ulcerative colitis patients at week 14. Response to therapy was accurately predicted by PIMS blood analysis in 100% of ulcerative colitis and 77% of Crohn disease patients. Overall prediction of clinical response with PIMS blood analysis was achieved with a 89% positive predictive value and a 82% negative predictive value. NPOT analysis revealed the heightened expression of the proteins ITGB7, ITGAV, ITG3, PF4, and ASGH in the peripheral blood of vedolizumab responders compared to nonresponders. Conclusions PIMS analysis of the blood of anti-TNF refractory IBD patients was able to stratify responders to vedolizumab therapy with high accuracy and specificity. NPOT technology could decipher underling molecular networks in the blood of responders, enabling subsequent personalized therapeutic approaches in IBD.

Funder

Takeda Pharmaceutical

Deutsche Forschungsgemeinschaft

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Engineering,General Environmental Science

Reference46 articles.

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