Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), represents a significant challenge in gastroenterology due to its chronic nature, unpredictable course, and impact on patients’ quality of life. The therapeutic landscape for IBD has evolved significantly with the advent of biologic agents targeting specific immune pathways. However, limitations, including partial efficacy, side effects, and development of resistance, highlight the ongoing need for innovative treatment approaches. This review explores emerging therapies in IBD, including novel biologics, small molecules, microbiome-based therapies, and gene and stem cell therapies. The article summarizes their mechanisms of action, clinical efficacy, safety profiles, and potential future directions in IBD management. Methods: This comprehensive narrative review synthesizes current knowledge and emerging developments in inflammatory bowel disease (IBD) therapeutics. Literature was identified through targeted selection of high-quality sources, including pivotal randomized controlled trials, systematic reviews and meta-analyses, regulatory approval documents, and clinical practice guidelines from major gastroenterology societies. Emphasis was placed on recent publications (2020–2024) to capture the rapidly evolving therapeutic landscape, with particular attention to FDA/EMA-approved therapies and promising late-stage investigational agents. Sources were prioritized based on clinical relevance, study quality, and regulatory status. This narrative approach was selected to provide comprehensive coverage of diverse therapeutic modalities spanning conventional treatments to cutting-edge techniques, including biologics, small molecules, microbiome-based therapies, gene therapy, and stem cell treatments. The review acknowledges the inherent limitations of non-systematic literature selection while prioritizing clinical utility and educational value for healthcare providers managing IBD patients in contemporary practice.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) remains technically challenging. Device-assisted ERCP (DAE-ERCP) is widely used for uncomplicated pancreaticobiliary disease but is associated with prolonged procedure times and high failure rates. Endoscopic ultrasound-directed transgastric ERCP (EDGE) offers high technical success but introduces additional cost and the risk of a persistent fistula. We aimed to prospectively identify intra-procedural predictors of DAE-ERCP failure and define an actionable, real-time threshold for early cross-over to EDGE. Methods: We prospectively evaluated consecutive RYGB patients undergoing DAE-ERCP at a tertiary referral center. Patients with established pre-procedural features associated with complex or low-yield DAE-ERCP were triaged directly to EDGE and excluded. Intra-procedural variables were recorded in real time. Univariate and multivariable logistic regression identified predictors of DAE-ERCP failure. Received operating characteristic (ROC) analysis determined optimal cutoffs for cross-over. Results: A total of 94 patients with RYGB underwent ERCP. Amongst these, 42 patients (11 males, 31 females) were included in the analysis and underwent DAE-ERCP with a success rate of 73.8% (n = 31). Significant risk factors of DAE-ERCP failure included excessive resistance to scope advancement (p < 0.0001), failure to reach the ampulla (p < 0.0001), patient position (p = 0.009), BMI (p = 0.004), and time to reach the jejuno-jejunal (J-J) anastomosis (p < 0.0001). Additionally, time needed to reach the J-J anastomosis of ≥23 min [OR 1.360 (95% CI: 1.079–1.713), p = 0.009], excess resistance to scope advancement [OR 2.223 (95% CI: 2.001–4.167)], and failure to reach the ampulla [OR 9.929 (95% CI: 2.004–4.033)] were statistically significant predictors of DAE-ERCP failure. When ≥2 predictors of BA-ERCP failure were present, the likelihood of DAE-ERCP failure was 2.370 with 95.50% sensitivity and 90% specificity with AUC= 0.929 (p = 0.0001). Conclusions: DAE-ERCP remains an effective first-line strategy in appropriately selecting RYGB patients without pre-procedural high-risk features. Real-time intra-procedural predictors can reliably identify impending failure. A structured algorithm incorporating both pre-procedural triage and intra-procedural checkpoints supports timely transition to EDGE, optimizing efficiency, safety, and resource utilization.