Regulatory Variants on the Leukocyte Immunoglobulin-Like Receptor Gene Cluster are Associated with Crohn's Disease and Interact with Regulatory Variants for TAP2.

BACKGROUND AND AIMS: Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations. METHODS: Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term. RESULTS: We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers). CONCLUSIONS: This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD.

Diagnosis of Crohn's disease and ulcerative colitis using the microbiome.

BACKGROUND: Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease resulting from dysregulation of the mucosal immune response and gut microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are difficult to distinguish, and differential diagnosis is essential for establishing a long-term treatment plan for patients. Furthermore, the abundance of mucosal bacteria is associated with the severity of the disease. This study aimed to differentiate and diagnose these two diseases using the microbiome and identify specific biomarkers associated with disease activity. RESULTS: Differences in the abundance and composition of the microbiome between IBD patients and healthy controls (HC) were observed. Compared to HC, the diversity of the gut microbiome in patients with IBD decreased; the diversity of the gut microbiome in patients with CD was significantly lower. Sixty-eight microbiota members (28 for CD and 40 for UC) associated with these diseases were identified. Additionally, as the disease progressed through different stages, the diversity of the bacteria decreased. The abundances of Alistipes shahii and Pseudodesulfovibrio aespoeensis were negatively correlated with the severity of CD, whereas the abundance of Polynucleobacter wianus was positively correlated. The severity of UC was negatively correlated with the abundance of A. shahii, Porphyromonas asaccharolytica and Akkermansia muciniphilla, while it was positively correlated with the abundance of Pantoea candidatus pantoea carbekii. A regularized logistic regression model was used for the differential diagnosis of the two diseases. The area under the curve (AUC) was used to examine the performance of the model. The model discriminated UC and CD at an AUC of 0.873 (train set), 0.778 (test set), and 0.633 (validation set) and an area under the precision-recall curve (PRAUC) of 0.888 (train set), 0.806 (test set), and 0.474 (validation set). CONCLUSIONS: Based on fecal whole-metagenome shotgun (WMS) sequencing, CD and UC were diagnosed using a machine-learning predictive model. Microbiome biomarkers associated with disease activity (UC and CD) are also proposed.

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.

Reliability and Validity of Korean Version of Crohn's and Ulcerative Colitis Questionnaire-8.

Background: Patients with inflammatory bowel disease (IBD) have a decreased quality of life (QoL), the improvement of which is a treatment goal. The CUCQ-8 is a verified simple and effective QoL measurement tool. We validated the Korean version of CUCQ-8 with the approval of its developer. Methods: We investigated the correlation between the Korean version of CUCQ-8 and the IBDQ-32 in patients with IBD. Results: In all, 147 subjects (male, 97 (66.0%); female, 50 (34.0%); mean age 36.2 ± 13.5 years) were analyzed. Cronbach's alpha coefficient of the CUCQ-8 was 0.833, indicating very high internal consistency. The Korean version of the CUCQ-8 showed a significant correlation with the IBDQ-32 and its subscales (correlation coefficient, >0.75). Conclusions: The Korean version of the CUCQ-8 has high reliability and construct validity and can be used to evaluate the QoL of patients with IBD.

The Common and Unique Pattern of Microbiome Profiles among Saliva, Tissue, and Stool Samples in Patients with Crohn's Disease.

This study aimed to elucidate common and unique microbiome patterns in saliva, intestinal tissue biopsy, and stool samples from patients with Crohn's disease (CD). Saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. A total of 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus, Pantoea, and Actinomyces from the saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus, which are commonly observed in saliva, stool, and tissue, can be considered a potential biomarker related to the diagnosis or prognosis of CD.

Development of a Machine Learning Model to Predict Non-Durable Response to Anti-TNF Therapy in Crohn's Disease Using Transcriptome Imputed from Genotypes.

Almost half of patients show no primary or secondary response to monoclonal anti-tumor necrosis factor α (anti-TNF) antibody treatment for inflammatory bowel disease (IBD). Thus, the exact mechanisms of a non-durable response (NDR) remain inadequately defined. We used our genome-wide genotype data to impute expression values as features in training machine learning models to predict a NDR. Blood samples from various IBD cohorts were used for genotyping with the Korea Biobank Array. A total of 234 patients with Crohn's disease (CD) who received their first anti-TNF therapy were enrolled. The expression profiles of 6294 genes in whole-blood tissue imputed from the genotype data were combined with clinical parameters to train a logistic model to predict the NDR. The top two and three most significant features were genetic features (DPY19L3, GSTT1, and NUCB1), not clinical features. The logistic regression of the NDR vs. DR status in our cohort by the imputed expression levels showed that the ß coefficients were positive for DPY19L3 and GSTT1, and negative for NUCB1, concordant with the known eQTL information. Machine learning models using imputed gene expression features effectively predicted NDR to anti-TNF agents in patients with CD.

Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial.

BACKGROUND AND AIMS: One-liter polyethylene glycol plus ascorbic acid (PEG-ASC) improves patient tolerability, but some patients still show low tolerability to a relatively high content of ASC. This study aimed to improve the tolerability and safety of 1-L PEG with low-dose ASC in comparison with standard 1-L and 2-L PEG-ASC. METHODS: This was a randomized, controlled, double-blinded, multicenter, noninferiority trial involving 215 healthy adults who underwent colonoscopy from June 2020 to January 2021. Efficacy, tolerability, and safety were compared among 1-L PEG with low-dose ASC (50% lower ASC concentration in group A and 25% lower ASC concentration in groups B and C) and standard 1-L and 2-L PEG-ASC with all split regimens. RESULTS: One-liter PEG with low-dose ASC (groups A-C) had similar bowel cleansing efficacies according to the Harefield Cleansing Scale and Boston Bowel Preparation Scale, without negative clinical performance, compared with standard 1-L and 2-L PEG-ASC preparation (all P > .1). One-liter PEG with low-dose ASC had better tolerability compared with 2-L PEG-ASC and less residual fluid retention in the stomach compared with 1-L PEG-ASC, proportional to the amount of ASC. No significant differences were found in the incidences of overall adverse events, mild adverse events, or death or in the occurrence of gastroduodenal erosion or ulcer in upper endoscopy. CONCLUSIONS: One-liter PEG with low-dose ASC (25%-50% reduction in dose) for bowel cleansing showed similar efficacy and safety compared with standard 1-L or 2-L PEG-ASC, better tolerability compared with 2-L PEG-ASC, and less residual gastric fluid retention compared with standard 1-L PEG-ASC. (Clinical trial registration number: KCT0005490.).

Second Victim Experience and Perception Discordance of the Colonoscopic Perforation.

BACKGROUND: Perforation is the most serious adverse event of colonoscopy, but rarely considered from the view of colonoscopists' second victim experience and perception discordance between colonoscopists and patients. AIMS: We aimed to evaluate colonoscopists' second victim experience and the perception discordance between colonoscopists and patients for the colonoscopic perforation. METHODS: A survey for colonoscopic perforation was performed for the colonoscopists and outpatients who visited the university hospital between February 1, 2020, and April 30, 2020. The questionnaire included questions regarding colonoscopists' satisfaction for the intervention strategies offered to patients and patient-colonoscopist perception on colonoscopic perforation. A modified Korean version of the "Second Victim Experience and Support Tool (K-SVEST)" was used to assess the second victim experiences and supportive resources for the colonoscopists. RESULTS: Survey results from 160 colonoscopists and 165 patients were analyzed. The colonoscopists' satisfaction scores were higher for strategies related to sufficient explanation, empathy, courteous listening, and monetary compensation. The scores of the K-SVEST for the second victim experience were highest in psychological distress, followed by loss of professional self-efficacy, colleague support, physical distress, non-work-related support, institutional support, and turnover intentions/absenteeism. Significant patient-colonoscopist discordance was noted for the same colonoscopic perforation scenario on the judgment of medical error, health professionals' apology, monetary compensation, and criminal penalties for the colonoscopists. CONCLUSIONS: Colonoscopists can suffer emotionally and physically from the second victim experience after colonoscopic perforation. In addition, the significant patient-colonoscopist discordance should be considered to make a better communication for the colonoscopic perforation.

Anastomotic leakage and chronic presacral sinus after transanal total mesorectal excision (taTME) for rectal cancer: A comparative study to laparoscopic TME.

BACKGROUND: Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME. METHODS: In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus. RESULTS: Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P = 0.569 and P = 1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P = 0.006). CONCLUSION: There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study.

BACKGROUND/AIMS: This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). METHODS: A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. RESULTS: A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients. CONCLUSIONS: ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Development of a Machine Learning Model to Distinguish between Ulcerative Colitis and Crohn's Disease Using RNA Sequencing Data.

Crohn's disease (CD) and ulcerative colitis (UC) can be difficult to differentiate. As differential diagnosis is important in establishing a long-term treatment plan for patients, we aimed to develop a machine learning model for the differential diagnosis of the two diseases using RNA sequencing (RNA-seq) data from endoscopic biopsy tissue from patients with inflammatory bowel disease (n = 127; CD, 94; UC, 33). Biopsy samples were taken from inflammatory lesions or normal tissues. The RNA-seq dataset was processed via mapping to the human reference genome (GRCh38) and quantifying the corresponding gene models that comprised 19,596 protein-coding genes. An unsupervised learning model showed distinct clusters of four classes: CD inflammatory, CD normal, UC inflammatory, and UC normal. A supervised learning model based on partial least squares discriminant analysis was able to distinguish inflammatory CD from inflammatory UC after pruning the strong classifiers of normal CD vs. normal UC. The error rate was minimal and affected only two components: 20 and 50 genes for the first and second components, respectively. The corresponding overall error rate was 0.147. RNA-seq analysis of tissue and the two components revealed in this study may be helpful for distinguishing CD from UC.

The real-world outcomes of vedolizumab in patients with ulcerative colitis in Korea: a multicenter retrospective study.

AIM: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. METHODS: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. RESULTS: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% (n = 43/77) achieved a clinical response and 18.2% (n = 14/77) achieved clinical remission. At week 14, 73.2% (n = 52/71) achieved a clinical response and 39.4% (n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% (n = 43/105) and 49.5% (n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). CONCLUSIONS: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

Long-term Outcomes after the Discontinuation of Anti-Tumor Necrosis Factor-α Therapy in Patients with Inflammatory Bowel Disease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study.

Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn's disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician's decision was associated with lower risk of relapse (vs patient's preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient's preference (n=6), and other factors (n=4). Conclusions: More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.

Development of a Clinical and Genetic Prediction Model for Early Intestinal Resection in Patients with Crohn's Disease: Results from the IMPACT Study.

Early intestinal resection in patients with Crohn's disease (CD) is necessary due to a severe and complicating disease course. Herein, we aim to predict which patients with CD need early intestinal resection within 3 years of diagnosis, according to a tree-based machine learning technique. The single-nucleotide polymorphism (SNP) genotype data for 337 CD patients recruited from 15 hospitals were typed using the Korea Biobank Array. For external validation, an additional 126 CD patients were genotyped. The predictive model was trained using the 102 candidate SNPs and seven sets of clinical information (age, sex, cigarette smoking, disease location, disease behavior, upper gastrointestinal involvement, and perianal disease) by employing a tree-based machine learning method (CatBoost). The importance of each feature was measured using the Shapley Additive Explanations (SHAP) model. The final model comprised two clinical parameters (age and disease behavior) and four SNPs (rs28785174, rs60532570, rs13056955, and rs7660164). The combined clinical-genetic model predicted early surgery more accurately than a clinical-only model in both internal (area under the receiver operating characteristic (AUROC), 0.878 vs. 0.782; n = 51; p < 0.001) and external validation (AUROC, 0.836 vs. 0.805; n = 126; p < 0.001). Identification of genetic polymorphisms and clinical features enhanced the prediction of early intestinal resection in patients with CD.

Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study.

BACKGROUND: We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. METHODS: Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission. RESULTS: Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. CONCLUSIONS: Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.