Dataset Information

Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis.

ABSTRACT:

Background and aim

Vedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut-homing memory T cells into the intestinal submucosa by antagonizing the interaction of α₄β₇ integrin with MAdCAM-1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real-world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy.

Methods

This was a single-center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty-two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively.

Results

In these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab.

Conclusions

In vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24.

SUBMITTER: Saito D

PROVIDER: S-EPMC8454470 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background:Vedolizumab inhibits ?4?7-mediated lymphocyte trafficking and is effective in ulcerative colitis (UC). This study evaluated drug and biomarker concentrations and patient outcomes during vedolizumab treatment in UC. Methods:Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.3-37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8-35.6 weeks) outcomes were compared with serum vedolizumab concentrations, antivedolizumab antibodies, and serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects model compared biomarker trajectories over time between clinical and endoscopic remitters and nonremitters. Results:Thirty-two patients were included. Soluble (s)-tumor necrosis factor (TNF)-?, s-?4?7, s-mucosal addressin cell adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with treatment. A linear mixed-effects model demonstrated that s-?4?7 (P = 0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule-1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052) decreased more rapidly in endoscopic remitters. In clinical remitters, higher week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6 ng/mL; P = 0.05) s-?4?7 were observed. In endoscopic remitters, week 2 (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P = 0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were lower. Conclusion:Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-?4?7 increased, whereas s-MAdCAM-1, s-VCAM-1, s-ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points, induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas maintenance s-?4?7 concentrations were higher in remitters.

Project description:AimsIn patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4β7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE).MethodsPatients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes.ResultsNineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab.ConclusionThis pilot study demonstrate that dual-band CLE is feasible to detect α4β7- and TNF-expressing cells. Positive α4β7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4β7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.