Introduction: Fecal calprotectin is a validated biomarker for assessing disease activity in patients with inflammatory bowel disease (IBD). Blood calprotectin concentrations are correlated with disease activity in numerous immune-mediated inflammatory diseases. The aim of this study was to prospectively assess the diagnostic accuracy of plasma calprotectin as a potential biomarker of remission in IBD patients. Methods: This prospective observational study enrolled 131 patients at the time of infliximab administration alongside clinical assessment and blood analyses on the same day. The primary endpoint was to assess the diagnostic accuracy of plasma calprotectin for predicting remission in patients with IBD. Results: Plasma calprotectin concentration ≤10.5 ng/mL had a sensitivity of 98.6%, specificity of 100%, positive predictive value of 100%, negative predictive value of 96.3%, and an area under the receiver operating characteristic (AUROC) curve of 0.999 for diagnosing remission in patients with ulcerative colitis (UC). Plasma calprotectin had poor diagnostic accuracy for diagnosing remission in Crohn’s disease. In UC, plasma calprotectin had significantly greater diagnostic accuracy than C-reactive protein for diagnosing remission (absolute difference between AUROCs, 0.06; 95% CI: 0.008 to 0.113; p = 0.03). Plasma calprotectin concentrations were not correlated with those measured in serum samples. The median serum-to-plasma calprotectin concentration ratio was 12-fold. Conclusion: Plasma calprotectin is a promising biomarker for predicting remission in UC patients treated with infliximab.

Introduction: Tofacitinib (TOF), a Janus kinase inhibitor, has emerged as an innovative treatment option for patients with moderate-to-severe ulcerative colitis (UC). However, the clinical course of patients who achieve induction and maintain remission followed by TOF tapering or withdrawal is unclear. We investigated the efficacy of TOF and the clinical course after TOF tapering or withdrawal in real-world clinical practice. Method: Thirty-two patients treated with TOF 20 mg/day for UC relapse between October 2018 and August 2023 were included in this single-center, retrospective observational study. Disease activity was defined by partial Mayo score (PMS), and remission was defined as PMS ≤2 and rectal bleeding score 0, other score ≤1. PMS before TOF 20 mg/day induction was compared with PMS at 8 weeks. Patients who achieved clinical remission were tapered to 10 mg/day, while those who requested for drug withdrawal were allowed. The relapse rate of the TOF 10 mg/day maintenance group and the TOF withdrawal group was compared. Both groups included patients who had maintained remission at 6 months after tapering TOF to 10 mg/day. In addition, the efficacy of TOF 20 mg/day reinduction therapy was also compared between patients who relapsed in the TOF 10 mg/day maintenance group and the TOF withdrawal group. Result: Twenty-three patients (71.9%) achieved induction of remission by 8 weeks after TOF 20 mg/day administration, with significantly lower PMS than before TOF (p < 0.0001). Ultimately, 27 patients (84.4%) achieved remission, 24 who achieved remission were tapered to 10 mg/day, whereas 18 were able to maintain remission for 6 months. Seven of the 18 eventually withdrew from TOF. There was no significant difference in relapse rates between the TOF 10 mg/day maintenance group (n = 11; follow-up, 525 [29–1,483] days) and the TOF withdrawal group (n = 7; follow-up, 284 [77–797] days) (5/11 [45.5%] vs. 3/7 [42.9%], log-rank test: p = 0.7091). All patients who received TOF 20 mg/day reintroduction therapy after relapse went into remission. Conclusion: In clinical practice, TOF 20 mg/day significantly induced induction of remission, and in patients who received 6 months of maintenance remission therapy with TOF 10 mg/day, the relapse rates between the TOF 10 mg/day maintenance group and the TOF withdrawal group were similar. After relapse, TOF 20 mg/day reintroduction therapy improved symptoms.

Introduction: Fatigue is an extraintestinal manifestation in patients with inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), with limited information on the underlying factors. This study aimed to determine the prevalence of fatigue and associated factors in IBD patients. Methods: This prospective observational study assessed 216 IBD patients treated with intravenous infliximab or vedolizumab. Clinically meaningful fatigue was defined using a visual analog scale with a score ≥4 (VAS-F, range 0–10). Further assessments included the patient health questionnaire (PHQ-8) for depressive symptoms, the IBD-control-8 questionnaire to evaluate subjective disease control and the fatigue impact scale (FIS) for patients’ quality of life (QoL). Demographic, clinical and laboratory data of the study population were collected and compared to identify fatigue-associated factors. Results: Overall, 53.2% (n = 115) of the IBD patients reported clinically meaningful fatigue with a higher prevalence in UC (63.0%) versus CD (47.4%). Among patients with CD, disease activity was significantly associated with fatigue symptoms (p < 0.001), whereas no such correlation was observed in UC patients (p = 0.85). Clinically meaningful fatigue symptoms were reported in 90.9% of patients with depressive symptoms (PHQ-8 ≥10). Furthermore, patients with fatigue were younger (40 vs. 42 years, p = 0.04), reported more frequent use of concomitant psychoactive and/or sedative medication (p = 0.03) and had lower IBD-control-8 scores (median 12 vs. 16 points, p < 0.001). Only minor differences were observed when comparing serum and fecal laboratory values of patients with fatigue symptoms to those without. Conclusion: Fatigue is highly prevalent among IBD patients treated with vedolizumab or infliximab and has a substantial impact on patients’ QoL. Fatigue and depressive symptoms were strongly associated, suggesting closer monitoring for depression and the use of psychoactive medication in patients with IBD.

Introduction: While previous reports have suggested an association between Wilson’s disease (WD) and ulcerative colitis (UC), we present the first case of asymptomatic WD diagnosed during the treatment course of UC. Case Presentation: A 14-year-old male receiving treatment for UC developed elevated liver enzymes without any related symptoms. After ruling out drug-induced liver toxicity and other possible causes of hepatitis, further investigation was initiated due to his sister’s subsequent diagnosis of WD. Tests revealed low serum ceruloplasmin and ATP7B gene variants, confirming WD. Following zinc therapy, liver enzymes have been normalized, and his previously refractory UC became under control. Conclusion: This case raises important questions about potential pathophysiological interactions between the two diseases.

Introduction: In Japan, the confirmed diagnosis of Crohn’s disease (CD) is based on a single, historically established set of clinical criteria. However, for patients who present with a perianal lesion (PL), the diagnostic pattern actually applied is unclear. Methods: We conducted a retrospective observational multicenter study among patients who presented with a PL without synchronous abdominal symptoms and were subsequently diagnosed with confirmed or probable CD according to the Japanese diagnostic criteria from May 1996 to April 2024. In total, 100 patients with confirmed CD and 10 with probable CD were identified and enrolled. Results: Among the 100 patients with confirmed CD, 72% met the criterion for the category “confirmed 1: main finding A (longitudinal ulcer) or B (cobblestone appearance).” In the same cohort, 35% met the criterion for the category “confirmed 2: main finding C (non-caseating epithelioid cell granuloma [NCEG]) with secondary finding a (extensive irregular-to-round ulcers or aphthae in the gastrointestinal tract) or b (characteristic anorectal lesions),” including 24% without the main finding A or B. Finally, 4% met the criterion for the category “confirmed 3: all secondary findings a, b, and c (characteristic gastric and duodenal lesions).” All 10 patients with probable CD were diagnosed based on secondary finding b only or secondary findings a and b. Conclusion: In cases of suspected CD due to initial PLs, histological investigation of NCEG and precise total gastrointestinal inspection should be conducted to confirm the diagnosis.

Introduction: This study aimed to develop and validate a burden scale for colonoscopy-specific experiences among patients with inflammatory bowel disease (IBD) and to assess its reliability and validity. Methods: Building upon previous research on patient experiences and perceptions of colonoscopy, a 33-item pain scale was developed. Content validity was assessed to refine the questionnaire. An online survey was conducted through an IBD patient community. The reliability of the scale was evaluated using Cronbach’s α coefficient and test-retest reliability. Validity was examined through factor analysis to assess construct validity and correlation coefficients with external criteria for criterion-related validity. Results: Of the 371 distributed questionnaires, 176 were returned, and data from 173 participants were included in the analysis. Item analysis and exploratory factor analysis yielded a 21-item scale with four distinct factors: pain during colonoscopy, burden with bowel preparation, anxiety and symptoms after colonoscopy, and difficulty in taking time off to receive colonoscopy. The scale demonstrated strong internal consistency (Cronbach’s α = 0.875) and test-retest reliability (intraclass correlation coefficient = 0.879). Criterion-related validity was supported by correlations with external measures, including the cognitive appraisal rating scale (r = 0.615), anxiety related to colonoscopy (r = 0.582), pain during colonoscopy (r = 0.544), and satisfaction with colonoscopy (r = −0.333). Conclusion: The newly developed burden scale for colonoscopy in patients with IBD demonstrated robust reliability and validity, indicating its potential utility as a clinical instrument for assessing the burden in this patient population.

Introduction: Lymphocytic esophagitis (LyE) represents a chronic inflammatory disease of the esophagus with low response rates to topical steroids. Thus, novel treatment options such as swallowed topical tacrolimus, particularly for refractory cases, are urgently needed. Methods: We retrospectively analyzed patients with LyE enrolled in the Swiss eosinophilic esophagitis database that received treatment with a swallowed tacrolimus syrup (1 mg bid). We compared clinical (visual analogue scale [VAS] 0–10), endoscopic (VAS, Endoscopic Reference Score [EREFS]), and histological (peak lymphocyte count) disease activity before versus after treatment. Results: Out of 17 LyE patients, we identified a total of 7 patients undergoing tacrolimus treatment (4 males, median age 71.3 years, IQR: 61.3–76.5, median diagnostic delay of 51.0 months, IQR: 24.5–62.0). Six patients had been previously treated with PPI, five with topical and/or systemic steroids. All patients were treated with topical tacrolimus corresponding to 1 mg bid (for a median of 13 weeks, IQR: 11–15). All patients had clinically, and histologically active disease at baseline. Topical tacrolimus treatment resulted in histological remission (<30 lymphocytes/hpf) in 3/7 patients (42.9%), while 4/7 patients achieved symptomatic remission (VAS for dysphagia ≤2, 57.1%). Overall, clinical (VAS 5 vs. 2, p = 0.0625) and endoscopic activity (VAS 5 vs. 2, p = 0.0625, and EREFS 3 vs. 2, p = 0.125) decreased. Measurement of tacrolimus trough levels in 4/7 patients (range 2.1–3.9 μg/L) revealed some degree of systemic absorption. Mild adverse events to the tacrolimus treatment were seen in 2 patients (esophageal candidiasis, hyposensitivity around lips). No impact on kidney function was observed during the treatment period. Conclusion: Topical tacrolimus appears to be a potential treatment option for severe LyE, particularly after failure of PPI and/or topical steroids. Further studies are needed, in particular regarding the optimal galenic formulation to avoid systemic absorption.

Background: Eosinophilic esophagitis (EoE) has been described as a chronic allergen/immune-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the mucosa. Summary: Over the past decades, EoE has been increasingly recognized in various geographical areas with a high socioeconomic development (mostly industrialized countries) and has evolved from an unknown to a clinically distinct disease with increasing prevalence and incidence. An average age at diagnosis between 30 and 50 years and a male predominance have been consistently observed. In both children and adults, EoE is clearly associated with allergies, predominantly food – but also aeroallergens. Most EoE patients present with a personal allergic background such as asthma, rhino-conjunctivitis, and oral allergy syndrome. Key Message: Knowledge of epidemiological characteristics is crucial for identifying risk factors and understanding of the pathogenic mechanisms. Background: Eosinophilic esophagitis (EoE) has been described as a chronic allergen/immune-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the mucosa. Summary: Over the past decades, EoE has been increasingly recognized in various geographical areas with a high socioeconomic development (mostly industrialized countries) and has evolved from an unknown to a clinically distinct disease with increasing prevalence and incidence. An average age at diagnosis between 30 and 50 years and a male predominance have been consistently observed. In both children and adults, EoE is clearly associated with allergies, predominantly food – but also aeroallergens. Most EoE patients present with a personal allergic background such as asthma, rhino-conjunctivitis, and oral allergy syndrome. Key Message: Knowledge of epidemiological characteristics is crucial for identifying risk factors and understanding of the pathogenic mechanisms.

Introduction: No real-world studies have compared efficacy of ustekinumab (UST) and risankizumab (RZB) for the treatment of Crohn’s disease (CD). Methods: We retrospectively collected the data of patients with CD treated with UST or RZB between May 2017 and March 2024 at the Institute of Science Tokyo and analyzed clinical remission rate at weeks 8 and 28 using Harvey-Bradshaw Index (HBI), with remission defined as a HBI ≤4. Result: A total of 111 patients who were treated with UST and 29 patients treated with RZB were included in the analysis. RZB had higher efficacy both at weeks 8 (82.8% vs. 62.2%, p = 0.0465) and 28 (79.3% vs. 56.8%, p = 0.0321) than UST in the full study cohort, and at weeks 8 (55.6% vs. 18.4%, p = 0.0352) and 28 (66.7% vs. 18.4%, p = 0.0083) in the patients with clinically active disease and anti-TNFα exposed patients. During the observation period, 1 patient with RZB (3.45%) experienced an adverse event that required hospitalization, and 1 patient in the UST group (0.900%) experienced an adverse event that led to treatment discontinuation. Conclusion: RZB may offer greater short-term efficacy than UST, with an acceptable safety profile in real-world settings.

Introduction: Autonomic imbalance has been reported to correlate with clinical remission in patients with ulcerative colitis (UC). This study evaluated heart rate variability (HRV), a potential digital biomarker, in patients with active UC using a smartwatch that is easy to handle. Methods: Patients with active UC were recruited for this prospective study. The patients’ HRV was measured via the Fitbit Inspire2™ linked via Bluetooth to their smartphone. HRV during nighttime sleep was obtained from continuous data. Patients were required to input the Simple Clinical Colitis Activity Index (SCCAI) score once daily by the application on their smartphones for 3 months. Results: Nine patients with UC were included. In clinically active disease, SCCAI scores showed a weak inverse relationship with parasympathetic activity, differences of successive R-R pulse intervals (RMSSD) (r = −0.44, p < 0.0001), high frequency (HF) (r = −0.42, p < 0.0001), and total autonomic nervous activity, low frequency (LF) (r = −0.43, p < 0.0001). Receiver operating characteristic analysis indicated that the RMSSD, HF, and LF were significantly higher in patients with active UC. Meanwhile, LF showed the most correlation with severity for bowel urgency scores. Conclusion: Longitudinal nighttime HRV recorded using a smartwatch is associated with disease activity in patients with active UC. In particular, RMSSD and HF, which are indices of the parasympathetic nervous system, have been suggested as potential digital biomarkers for UC.