Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn's disease activity confirmed by balloon-assisted enteroscopy.

BACKGROUND/AIMS: Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn's disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy. METHODS: One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed. RESULTS: Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 µg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 µg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse. CONCLUSIONS: The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.

Efficacy and safety of risankizumab for Crohn's disease in patients from Asian countries: a post hoc subanalysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies.

BACKGROUND AND AIM: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients. METHODS: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks. RESULTS: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients. CONCLUSION: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.

Maintenance Risankizumab Sustains Induction Response in Patients with Crohn's Disease in a Randomized Phase 3 Trial.

BACKGROUND AND AIMS: Durable clinical remission, endoscopic healing, and biomarker normalization are key treatment goals for Crohn's disease. The selective anti-interleukin-23 p19 inhibitor risankizumab has demonstrated efficacy and safety in moderately to severely active Crohn's disease. This post-hoc analysis of data from the pivotal risankizumab maintenance study assessed whether risankizumab maintenance therapy sustained the clinical and endoscopic outcomes achieved with risankizumab induction therapy. METHODS: We evaluated 462 patients who achieved a clinical response to risankizumab intravenous induction treatment and were re-randomized to receive subcutaneous risankizumab 360 mg, subcutaneous risankizumab 180 mg, or placebo [withdrawal] every 8 weeks for 52 weeks in the randomized, controlled FORTIFY maintenance study. Maintenance of clinical, endoscopic, and biomarker endpoints at week 52 among patients who achieved these endpoints after 12 weeks of induction treatment was evaluated. RESULTS: A significantly higher proportion of patients receiving maintenance treatment with risankizumab 360 or 180 mg compared with placebo [withdrawal] maintained Crohn's Disease Activity Index remission [68.6%, 70.8%, vs 56.3%; p < 0.05], stool frequency/abdominal pain remission [69.2%, 64.1%, vs 50.5%; p < 0.01], endoscopic response [70.2%, 68.2%, vs 38.4%; p < 0.001], endoscopic remission [74.4%, 45.5%, vs 23.9%; p < 0.05], and Simple Endoscopic Score for Crohn's Disease of 0-2 [65.5%, 36.7%, vs 21.9%]. Most patients [56.8-83.3%] who achieved normalized faecal calprotectin or C-reactive protein during induction sustained them with maintenance risankizumab. CONCLUSIONS: Subcutaneous risankizumab maintenance therapy results in durable improvement in clinical and endoscopic outcomes over 1 year in patients with moderately to severely active Crohn's disease. CLINICAL TRIAL REGISTRATION NUMBER: NCT03105102.

COVID-19 severity is associated with the risk of gastrointestinal bleeding.

OBJECTIVE: The association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding. DESIGN: A multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding. RESULTS: 12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342). CONCLUSION: The severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding.

Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study.

BACKGROUND: The YOu and Ulcerative colitis: Registry and Social network (YOURS) is a large-scale, multicenter, patient-focused registry investigating the effects of lifestyle, psychological factors, and clinical practice patterns on patient-reported outcomes in patients with ulcerative colitis in Japan. In this initial cross-sectional baseline analysis, we comprehensively explored impacts of symptom severity or proctocolectomy on nine patient-reported outcomes. METHODS: Patients receiving tertiary care at medical institutions were consecutively enrolled in the YOURS registry. The patients completed validated questionnaires on lifestyle, psychosocial factors, and disease-related symptoms. Severity of symptoms was classified with self-graded stool frequency and rectal bleeding scores (categories: remission, active disease [mild, moderate, severe]). The effects of symptom severity or proctocolectomy on nine scales for quality of life, fatigue, anxiety/depression, work productivity, and sleep were assessed by comparing standardized mean differences of the patient-reported outcome scores. RESULTS: Of the 1971 survey responses analyzed, 1346 (68.3%) patients were in remission, 583 (29.6%) had active disease, and 42 (2.1%) had undergone proctocolectomy. A linear relationship between increasing symptom severity and worsening quality of life, fatigue, anxiety, depression, and work productivity was observed. Patients with even mild symptoms had worse scores than patients in remission. Patients who had undergone proctocolectomy also had worse scores than patients in remission. CONCLUSIONS: Ulcerative colitis was associated with reduced mood, quality of life, fatigue, and work productivity even in patients with mild symptoms, suggesting that management of active ulcerative colitis may improve patient-reported outcomes irrespective of disease severity. (UMIN Clinical Trials Registry: UMIN000031995, https://www.umin.ac.jp/ctr/index-j.htm ).

Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD).

BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD]. RESULTS: Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities. CLINICAL TRIALS REGISTRY: University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

Transmural Remission Characterized by High Biologic Concentrations Demonstrates Better Prognosis in Crohn's Disease.

BACKGROUND: The importance and pathophysiology of transmural healing in patients with Crohn's disease [CD] remains to be verified. We aimed to examine the association between serum concentrations of biologics and transmural remission evaluated via magnetic resonance enterography [MRE]. METHODS: We enrolled patients with CD who received maintenance biologics 1 year after induction and prospectively followed up for at least 1 year after baseline laboratory, endoscopic and MRE examination. We evaluated the relationship between baseline factors including the presence of transmural remission and patient prognosis, as well as between serum concentrations and transmural remission. RESULTS: We included 134 patients, of whom 65, 31, 27 and 11 received infliximab, adalimumab, ustekinumab and vedolizumab, respectively. Those who achieved transmural remission showed a lower risk of hospitalization and surgery than those who did not achieve remission [p < 0.01]. Adjusted hazard ratios of transmural remission for predicting hospitalization and surgery were 0.11 and 0.02, respectively, which were lower than those of clinical remission, biochemical remission and endoscopic remission. Regarding serum concentrations, the median concentration was higher in patients with transmural remission than in patients with transmural activity for all agents [p < 0.01 for infliximab, p = 0.04 for adalimumab, p < 0.01 for ustekinumab, p = 0.08 for vedolizumab]. CONCLUSIONS: Transmural remission was the best predictor for prognosis in CD patients who received maintenance biologic therapy. High drug concentration levels were associated with transmural remission confirmed via MRE.

Hemorrhagic gastric ulcer in a patient with Behcet's disease successfully treated with infliximab.

Behcet's disease (BD) is a multisystem immune-mediated inflammatory disorder that occasionally involves the gastrointestinal tract. Reports on gastrointestinal involvement of BD are relatively rare, of which gastroduodenal involvement is particularly rare. Endoscopic features of gastroduodenal lesions are unknown, and treatment strategies have not been established. In this report, we present the case of a 72-year-old female with gastrointestinal BD who presented with extensive gastroduodenal ulcers and hematemesis that were resistant to colchicine and corticosteroid treatment, which were subsequently successfully treated with infliximab. We also review the current literature on the gastroduodenal involvement of BD. Although rare, the case highlights the importance of being aware of upper gastrointestinal manifestations of BD, as well as demonstrating the potential of infliximab to treat corticosteroid-resistant cases.

Serum Leucine-Rich α2 Glycoprotein: A Novel Biomarker for Transmural Inflammation in Crohn's Disease.

INTRODUCTION: Leucine-rich alpha-2 glycoprotein (LRG) is a newly studied biomarker for inflammatory diseases. This study aimed to investigate whether LRG can be used for evaluating transmural activity in patients with Crohn's disease (CD). METHODS: We performed magnetic resonance enterography (MRE) in 227 consecutive patients with CD from June 2020 to August 2021. We prospectively compared MRE findings with clinical and laboratory data including LRG. MRE was evaluated using 2 validated scoring systems, and transmural inflammation was defined as having a maximum simplified magnetic resonance index of activity (sMaRIA) score of ≥4 and a 5-point classification score of ≥9, respectively. RESULTS: The correlation between LRG and the total MRE score showed a positive correlation ( r = 0.576 for the sMaRIA score, P < 0.01, and r = 0.633 for the 5-point score, P < 0.01). Serum concentrations of LRG significantly increased as MRE scores increased ( P < 0.01). The area under the curve of LRG for a sMaRIA score of ≥4 and a 5-point score of ≥9 was 0.845 and 0.869, respectively, which was significantly higher than that of CDAI ( P < 0.01) or C-reactive protein ( P < 0.01). LRG levels of ≥14 µg/mL had a 67% sensitivity and 90% specificity for a sMaRIA score of ≥4 and a 73% sensitivity and 89% specificity for a 5-point score of ≥9. Patients with high LRG levels were also strongly associated with CD-related hospitalization, surgery, and clinical relapse compared with those with low LRG levels ( P < 0.01 for all). DISCUSSION: LRG is a highly accurate serum biomarker for detecting transmural activity in patients with CD. Results need to be validated in further multicenter studies.

A case of venous stasis colitis possibly caused by eplerenone.

A 50-year-old man was referred to our hospital for colitis with abdominal pain and diarrhea that had persisted for more than 8 months. 9 months earlier, he had been treated for fulminant eosinophilic myocarditis. During steroid therapy, ulceration appeared in the esophagus, stomach and large intestine. The biopsy results showed cytomegalovirus (CMV) inclusion bodies, and the patient was diagnosed with CMV gastrocolitis and treated with ganciclovir. Colonoscopy 7 months earlier revealed ischemia-like segmental colitis 10 cm in length in the hepatic flexure without evidence of CMV infection. Colonoscopy after 1 month and 3 months showed no improvement. We suspected drug-induced focal ischemic colitis, and discontinued eplerenone. Colonoscopy 2 months after withdrawal of eplerenone showed improvement in colitis, and colonoscopy 8 months later showed ulcer healing. Venous disorders are cautioned as a known side effect of eplerenone, but this is the first report of venous stasis colitis thought to be caused by eplerenone.

Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings.

PURPOSE: To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). METHODS: This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. RESULTS: Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. CONCLUSION: The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.

Characteristics of adult patients newly diagnosed with Crohn's disease: interim analysis of the nation-wide inception cohort registry study of patients with Crohn's disease in Japan (iCREST-CD).

BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.

Serum Levels of Infliximab Biosimilar in a Child Delivered From a Mother Treated for Ulcerative Colitis.

The infliximab biosimilar CT-P13 is used for the treatment of ulcerative colitis. We report for the first time the serum drug levels and long-term health status of the child of a patient treated with CT-P13 throughout her pregnancy.

Mucosal healing of small intestinal stricture is associated with improved prognosis post-dilation in Crohn's disease.

BACKGROUND: Small intestinal stricture is a major cause for surgery in Crohn's disease (CD). Endoscopic balloon dilation (EBD) is performed for small intestinal strictures to avoid surgery, often repeatedly. However, factors that are associated with prognosis after EBD of small intestinal strictures remain poorly investigated. Mucosal healing is the therapeutic target in CD. We aimed to investigate the impact of mucosal healing defined by the presence of ulcers at the small intestinal stricture site on the prognosis of EBD in CD patients. METHODS: We retrospectively included patients with CD who underwent initial EBD for endoscopically impassable small intestinal strictures from January 2012 to March 2020 at a single center. The association between presence of ulcer at the stricture site and surgery after EBD was examined by Cox proportional hazards model. RESULTS: Of the 98 patients included, 63 (64.3%) had ulcer at the stricture site. 20 (31.7%) of these patients underwent surgery for the stricture in due course, whereas 4 (11.4%) of the patients without ulcer of the stricture underwent surgery. In multivariate analysis, patients with ulcer of the stricture had a significantly higher risk for surgery than those without ulcer (hazard ratio 4.84; 95% confidence interval 1.58-14.79). CONCLUSION: Mucosal healing at the stricture site indicated a favorable prognosis after EBD for small intestinal strictures in CD.

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

Deep neural network for video colonoscopy of ulcerative colitis: a cross-sectional study.

BACKGROUND: A combination of endoscopic and histological evaluation is important in the management of patients with ulcerative colitis. We aimed to adapt our previous deep neural network system (deep neural ulcerative colitis [DNUC]) to full video colonoscopy and evaluate its validity in the real-time detection of histological mucosal inflammation. METHODS: In this multicentre, cross-sectional study, we prospectively enrolled consecutive patients (≥15 years) with ulcerative colitis who had an indication for colonoscopy at five hospitals in Japan. Patients in clinical remission were randomly assigned (1:2) to study 1 and study 2. Those with clinically active disease were assigned to study 2 only. Study 1 assessed the validity of real-time histological assessment using DNUC and study 2 validated the consistency of endoscopic scoring between DNUC and experts. The primary endpoint for study 1 was comparison of the results judged by DNUC (healing or active) with biopsy specimens evaluated by pathologists. In study 2, the primary endpoint was the ability of DNUC to determine the Ulcerative Colitis Endoscopic Index of Severity score compared with centrally evaluated scoring by inflammatory bowel disease endoscopy experts. FINDINGS: From April 1, 2020, to March 31, 2021, 770 patients (180 in study 1 and 590 in study 2) were enrolled. Using real-time histological evaluation, DNUC was able to evaluate the presence or absence of histological inflammation in 729 (81%) of 900 biopsy specimens. For predicting histological remission, the DNUC had a sensitivity of 97·9% (95% CI 97·0-98·5) and a specificity of 94·6% (91·1-96·9). Moreover, its positive predictive value was 98·6% (97·7-99·2) and negative predictive value was 92·1% (88·7-94·3). The intraclass correlation coefficient between DNUC and experts for endoscopic scoring was 0·927 (95% CI 0·915-0·938). INTERPRETATION: DNUC provided consistently accurate endoscopic scoring and showed potential for reducing the number of biopsies required. This system is an objective and consistent application for video colonoscopy that has potential for use in various medical situations. FUNDING: Tokyo Medical and Dental University and Sony.