biostudies-literatureGonzalez CGInstitutional Research and Career DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNational Institute of HealthResearch Council at the KU LeuvenUniversity Hospitals LeuvenClinical Research FundNIH/NIDDK U planning grantNIGMS NIH HHSNIH/NIDDK1536-1545https://www.ebi.ac.uk/biostudies/studies/S-EPMC12102473biostudies-literatureUnknown30(9)<h4>Background</h4>Crohn's disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract. Common biologic families used to treat Crohn's are tumor necrosis factor (TNF)-α blockers (infliximab and adalimumab) and immune cell adhesion blockers (vedolizumab). Given their differing mechanisms of action, the ability to monitor response and predict treatment efficacy via easy-to-obtain blood draws remains an unmet need.<h4>Methods</h4>To investigate these gaps in knowledge, we leveraged 2 prospective cohorts (LOVE-CD, TAILORIX) and profiled their serum using high-dimensional isobaric-labeled proteomics before treatment and 6 weeks after treatment initiation with either vedolizumab or infliximab.<h4>Results</h4>The proportion of patients endoscopically responding to treatment was comparable among infliximab and vedolizumab cohorts; however, the impact of vedolizumab on patient sera was negligible. In contrast, infliximab treatment induced a robust response including increased blood-gas regulatory response proteins, and concomitant decreases in inflammation-related proteins. Further analysis comparing infliximab responders and nonresponders revealed a lingering innate immune enrichments in nonresponders and a unique protease regulation signature related to clotting cascades in responders. Lastly, using samples prior to infliximab treatment, we highlight serum protein biomarkers that potentially predict a positive response to infliximab treatment.<h4>Conclusions</h4>These results will positively impact the determination of appropriate patient treatment and inform the selection of clinical trial outcome metrics.Inflammatory bowel diseasesCrohn's Patient Serum Proteomics Reveals Response Signature for Infliximab but not Vedolizumab.PMC12102473R01 DK131005SDDRC P30K12, K12GM068524DK1266261R01DK131005K12 GM068524U34 DK126626D'Haens GVerstockt BGonzalez DJGonzalez CGDulai PSStevens TWfalseCrohn's Patient Serum Proteomics Reveals Response Signature for Infliximab but not Vedolizumab.<h4>Background</h4>Crohn's disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract. Common biologic families used to treat Crohn's are tumor necrosis factor (TNF)-α blockers (infliximab and adalimumab) and immune cell adhesion blockers (vedolizumab). Given their differing mechanisms of action, the ability to monitor response and predict treatment efficacy via easy-to-obtain blood draws remains an unmet need.<h4>Methods</h4>To investigate these gaps in knowledge, we leveraged 2 prospective cohorts (LOVE-CD, TAILORIX) and profiled their serum using high-dimensional isobaric-labeled proteomics before treatment and 6 weeks after treatment initiation with either vedolizumab or infliximab.<h4>Results</h4>The proportion of patients endoscopically responding to treatment was comparable among infliximab and vedolizumab cohorts; however, the impact of vedolizumab on patient sera was negligible. In contrast, infliximab treatment induced a robust response including increased blood-gas regulatory response proteins, and concomitant decreases in inflammation-related proteins. Further analysis comparing infliximab responders and nonresponders revealed a lingering innate immune enrichments in nonresponders and a unique protease regulation signature related to clotting cascades in responders. Lastly, using samples prior to infliximab treatment, we highlight serum protein biomarkers that potentially predict a positive response to infliximab treatment.<h4>Conclusions</h4>These results will positively impact the determination of appropriate patient treatment and inform the selection of clinical trial outcome metrics.2024-01-01T00:00:00Z2024 Sep2026-06-02T00:30:35.923Z2026-05-24T03:07:08.824ZS-EPMC121024733836720910.1093/ibd/izae016