Introduction
Linked Color Imaging (LCI) is an endoscopic system that emphasizes the red mucosal color to identify subtle areas of inflammation. Endoscopic imaging, including LCI classification and LCI index, has been reported as a predictor of histological healing (HH) in ulcerative colitis (UC). Endoscopic changes (LCI classification, LCI index) in vedolizumab treatment have not been reported to date.
Aims & Methods
This study aimed to evaluate endoscopic remission and HH using LCI endoscopy at week 22 of vedolizumab treatment in patients with moderate to severe UC. This was a phase 4, multicenter, open-label, single-arm, prospective study involving 12 patients with moderately to severely active UC receiving vedolizumab. Vedolizumab was administered for 54 weeks. Endoscopy and mucosal sampling from most inflamed sites or the patient’s rectum when all sites had equal endoscopic severity were performed at weeks 0, 22, and 54 to assess the LCI index, LCI classification, Mayo endoscopic score (MES), Nancy score (If MES = 0, it was collected from the rectum). This study was also evaluated a variety of possible factors such as fecal calprotectin, serum vedolizumab concentration and mucosal gene expression associated with changes induced by vedolizumab. LCI index was numerically evaluated for the redness of a 40-pixel square area within the LCI image. LCI classification was defined by assigning one of the three categories (A, no redness; B, redness with visible vessels; C, intense redness without visible vessels). HH was defined as a Nancy score ≤1, and clinical outcomes were compared between HH and non-HH groups. Correlation coefficients between LCI endoscopy and other clinical markers (MES, Nancy score, fecal calprotectin and vedolizumab concentration) were analyzed at weeks 0, 22, and 54. Gene expression analysis was performed on 374 genes, comparing HH (n=8) vs. non-HH (n=3) and LCI classification A (n=5) vs. LCI classification B and C (n=6) at week 22. Biomarkers common to HH and LCI-A were identified as LCI-Deep remission (L-DR) markers.
The study was registered with the Japan Clinical Trial Registry (Identifier: UMIN000042855).
Results
At week 22, 66.7% (8/12) achieved histological healing (HH), while 50.0% (6/12) met LCI classification A criteria. The LCI index change from baseline showed a statistically significant difference between HH and non-HH (week 22: p=0.021; week 54: p=0.011).Correlation analysis demonstrated that LCI index was significantly associated with: MES (week 22: ρ=0.729, week 54: ρ=0.789), Nancy score (week 22: ρ=0.695, week 54: ρ=0.725), fecal calprotectin (week 22: ρ=0.555, week 54: ρ=0.783), vedolizumab concentration (week 22: ρ=0.758, week 54: ρ=-0.418). Gene expression analysis identified IL1B, CXCL11, CD38, CSF2RB, PTPN6, CD86, NFKB2, IFNAR2, STAT1, GNAI2, FES and IRF9 as L-DR markers, as they were commonly associated with both HH and LCI classification A. There are genes involved in NF-κB signaling pathway and JAK-STAT signaling pathway associated with UC. HH and LCI endoscopy have been found to correlate well but do not perfectly align.
In this study, we proposed a definition of L-DR, which encompasses both HH and LCI endoscopic remission.
Conclusion
This study introduces L-DR as a novel definition for combined endoscopic (LCI-A) and HH (Nancy score ≤1) in UC patients receiving vedolizumab. Additionally, we identified candidate L-DR biomarkers that may serve as potential indicators of deep remission.
Disclosure
Tomohisa Takagi, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Mitsubishi Tanabe Pharma Corporation,
Collaborative research fund from PreMedica Inc.,
Lecture fees by Mochida Pharma. Co., Ltd., Yanssen Pharmaceutical K.K., EA Pharma. Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Towa Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc.
Kazuhiko Uchiyama, Male, ( Kyoto Prefectural University of Medicine, Kyoto, Japan):
Collaboration research fund from Janssen Pharma. K.K.
Lecture fee by Mitsubishi Tanabe Pharma. Co. Ltd. and Janssen Pharma. K.K.
Yuji Naito, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Taiyo Kagaku Co. Ltd., Morinaga Co. Ltd., Miyarisan Pharma Co. Ltd, Morishita-Jintan Co. Ltd., Fujikko Co. Ltd., Mizkan Co. Ltd., Mykinso Co. Ltd.
Collaboration research fund from Takeda Pharma. Co. Ltd. and Taiyo Kagaku Co., Ltd.
Lecture fees by Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., Biofermin. Co. Ltd., Otsuka Pharma. Co. Ltd., and Miyarisan Pharma. Co. Ltd.
