Trending Topics in Gastroenterology | GastroAGI

Vitamin D Supplementation Improves Real-World IBD Outcomes : CGH | Jun 2026

Introduction: Vitamin D deficiency is highly prevalent among patients with inflammatory bowel disease (IBD) and has been associated with increased disease activity, impaired mucosal healing, reduced quality of life, and higher healthcare utilization. Beyond its established role in bone health, vitamin D exerts important immunomodulatory effects that may influence intestinal inflammation. Despite these biological advantages, the real-world clinical benefits of vitamin D supplementation in IBD have remained uncertain. Problem Statement: Although vitamin D deficiency is frequently identified and treated in patients with IBD, evidence supporting its impact on meaningful clinical outcomes such as corticosteroid requirements, emergency department visits, and hospitalizations is limited. Determining whether supplementation translates into measurable improvements in disease burden is important for optimizing routine IBD care. Summary: This large real-world study evaluated the impact of vitamin D supplementation on clinical outcomes in patients with IBD receiving care within a national healthcare system. The investigators found that vitamin D supplementation was associated with a reduction in IBD-related emergency department visits, hospitalizations, and corticosteroid use compared with patients who did not receive supplementation. These findings were consistent across multiple analytical approaches, strengthening the reliability of the observed associations. The study suggests that correction of vitamin D deficiency may contribute to improved disease control and reduced healthcare utilization in routine clinical practice. Given its low cost, favorable safety profile, and widespread availability, vitamin D supplementation represents an attractive adjunctive strategy in the management of IBD. Importantly, the benefits observed extended beyond laboratory correction of deficiency and were linked to clinically meaningful outcomes that directly affect patients and healthcare systems. While the observational nature of the study prevents definitive conclusions regarding causality, the results support a proactive approach to screening for and treating vitamin D deficiency in IBD populations. Future prospective trials are needed to determine optimal supplementation regimens, identify target vitamin D levels, and clarify the mechanisms through which vitamin D may influence long-term disease outcomes.

Darvadstrocel Fails to Improve Remission in Complex Perianal Crohn’s Fistulas : Gastroenterology | June 2026

Introduction: Crohn's Disease–associated complex perianal fistulas remain one of the most difficult complications in inflammatory bowel disease management, causing major morbidity, impaired quality of life, and high rates of treatment failure. Mesenchymal stem-cell therapy emerged as a promising regenerative strategy after earlier trials suggested benefit with Darvadstrocel in fistulizing Crohn’s disease. Problem Statement: Although the original ADMIRE-CD trial demonstrated encouraging remission rates with darvadstrocel, questions remained regarding reproducibility across broader international populations and contemporary biologic-exposed patients. Confirmation in a larger phase 3 trial was essential before establishing stem-cell therapy as a standard treatment for complex perianal Crohn’s fistulas. Summary: The ADMIRE CD II trial was a large international phase 3 randomized placebo-controlled study evaluating the efficacy and safety of darvadstrocel in patients with refractory complex perianal Crohn’s fistulas. The study enrolled adults with Crohn’s disease who had complex perianal fistulas with limited internal and external openings and inadequate response to immunosuppressive or biologic therapies. A total of 568 patients were randomized to receive either darvadstrocel or placebo following standardized surgical preparation including fistula curettage and closure of internal openings. The primary endpoint was combined remission at week 24, defined as closure of all treated external fistula openings together with absence of significant collections on imaging. Importantly, the trial failed to meet its primary endpoint. Combined remission occurred in 48.8% of patients treated with darvadstrocel compared with 46.3% in the placebo group, with no statistically significant difference between treatment arms. Similarly, key secondary endpoints including clinical remission rates and time to remission also failed to demonstrate superiority of darvadstrocel over placebo. Despite the negative efficacy findings, the safety profile remained reassuring. Treatment-emergent adverse events occurred at similar rates in both groups, and no new safety concerns related to stem-cell therapy were identified. The study is highly important because it represents one of the largest and most rigorous randomized evaluations of cellular therapy in fistulizing Crohn’s disease. The findings contrast with the earlier positive ADMIRE-CD study and raise important questions regarding patient selection, procedural standardization, placebo response rates, and the reproducibility of stem-cell therapeutic benefit. One notable aspect of the trial is the relatively high remission rate observed in the placebo arm, likely reflecting the substantial contribution of optimized surgical management, internal opening closure, and multidisciplinary fistula care. This emphasizes that meticulous surgical preparation itself remains a critical determinant of fistula healing outcomes. Clinically, the results suggest that darvadstrocel cannot currently be considered universally superior to optimized surgical and medical management for complex perianal fistulas. The study also highlights the broader challenge of translating promising regenerative therapies into consistently effective real-world inflammatory bowel disease treatments. Importantly, the absence of new safety signals preserves interest in cellular therapies and suggests that future studies may still identify responsive subgroups or improved delivery strategies. Potential areas for future investigation include biomarker-guided patient selection, integration with biologic therapy optimization, repeated stem-cell administration, and identification of fistula phenotypes more likely to respond to regenerative approaches. The trial further reinforces the need for standardized composite endpoints in fistulizing Crohn’s disease research, given the complexity of correlating clinical drainage closure with radiologic healing. Overall, ADMIRE CD II demonstrated that darvadstrocel did not significantly improve remission rates compared with placebo in complex perianal Crohn’s disease, underscoring the ongoing therapeutic challenges in fistulizing disease despite encouraging earlier regenerative medicine data.

AI and Multi-Omics Redefine Postoperative Crohn’s Recurrence : Gut | 2026

Introduction Crohn's Disease postoperative recurrence remains one of the greatest challenges after intestinal resection, with endoscopic recurrence occurring in the majority of patients within the first year. Despite advances in biologic therapy and surgical technique, accurately predicting and monitoring recurrence remains difficult. Problem Statement Current surveillance strategies, including ileocolonoscopy and Faecal Calprotectin, have important limitations related to sensitivity, standardization and ability to capture transmural or biologically evolving disease. Additionally, variability in anastomotic techniques and disease phenotypes complicates individualized risk assessment. Summary This forward-looking review explores how advanced imaging, artificial intelligence and multi-omics technologies may transform the future management of postoperative recurrence in Crohn’s disease. The authors emphasize that postoperative recurrence is biologically heterogeneous and likely driven by complex interactions among immune dysregulation, microbial shifts, genetic susceptibility and tissue remodeling pathways. Traditional endoscopic assessment primarily evaluates mucosal disease activity and may underestimate deeper or early inflammatory changes. Emerging technologies aim to overcome this limitation through more comprehensive structural and biologic characterization. High-resolution endoscopic techniques including Confocal Laser Endomicroscopy and endocytoscopy now permit in vivo microarchitectural assessment of anastomotic tissue, potentially enabling earlier recognition of recurrence before overt ulceration develops. Parallel advances in Intestinal Ultrasound and cross-sectional imaging are reshaping postoperative surveillance by allowing non-invasive transmural evaluation. These modalities may detect bowel wall thickening, vascularity and mesenteric inflammation that precede clinical relapse. The review highlights the growing role of multi-omics approaches including genomics, transcriptomics, proteomics, metabolomics and metagenomics in identifying biologic signatures associated with postoperative recurrence risk. These technologies are uncovering novel pathways involved in fibrosis, immune activation, epithelial barrier dysfunction and microbiome-host interactions, providing mechanistic insight beyond conventional clinical risk factors. Artificial intelligence emerges as a central theme of the review. AI-enabled systems may integrate clinical variables, imaging features, endoscopic patterns and omics-derived biomarkers into predictive multimodal models capable of individualized recurrence forecasting. Such models could ultimately support precision medicine strategies by identifying which patients require aggressive postoperative biologic therapy versus those suitable for lower-intensity monitoring. Importantly, AI-assisted endoscopy may also improve lesion detection, reduce interobserver variability and standardize postoperative scoring systems that currently suffer from significant subjectivity. The article additionally addresses the evolving role of surgical factors, including anastomotic configuration, in shaping recurrence biology and surveillance interpretation. Clinically, this work reflects a broader transition in inflammatory bowel disease management—from reactive treatment of established recurrence toward proactive biologically informed prevention. The review is especially relevant because postoperative Crohn’s disease recurrence remains associated with repeated surgeries, cumulative bowel damage and progressive disability despite modern therapeutics. However, the authors appropriately emphasize that most emerging technologies remain investigational. Prospective validation, harmonization of methodologies and integration into real-world clinical workflows are still required before widespread implementation. Major barriers include cost, accessibility, data standardization and the complexity of integrating multi-dimensional datasets into routine care pathways. Future directions will likely involve hybrid predictive platforms combining AI-enhanced imaging, molecular biomarkers and longitudinal patient-specific data to dynamically guide postoperative management. Overall, this review outlines a future precision-medicine framework for postoperative Crohn’s disease, where AI-enabled imaging and multi-omics technologies may enable earlier detection, personalized risk stratification and more targeted prevention of recurrence.

FIT Plus Calprotectin Improves Young-Onset GI Triage : Gut | May 2026

Introduction Inflammatory Bowel Disease and early-onset Colorectal Cancer are increasingly encountered in younger adults presenting with lower gastrointestinal symptoms. However, distinguishing inflammatory disease from neoplasia in this age group remains diagnostically challenging. Problem Statement The low prevalence of colorectal cancer and higher prevalence of inflammatory bowel disease in younger patients reduce the discriminatory performance of the Faecal Immunochemical Test when used alone. Current pathways risk missed inflammatory disease, delayed referral and inefficient triage. Summary This prospective primary-care pilot study evaluated whether combining FIT with Faecal Calprotectin using the York Faecal Calprotectin Care Pathway could improve diagnostic discrimination between colorectal cancer and inflammatory bowel disease in younger adults. Nearly 900 patients were prospectively enrolled, with a median age of 35 years, representing a clinically important population increasingly seen in both primary care and gastroenterology clinics. The study demonstrated a major limitation of FIT-only strategies in younger populations. Although FIT showed excellent negative predictive value for the composite endpoint of colorectal cancer or IBD, it failed to identify a substantial proportion of patients with Crohn's Disease. Importantly, FIT alone missed almost half of Crohn’s disease diagnoses, highlighting the biologic limitation of relying solely on occult bleeding markers in inflammatory bowel disease assessment. By contrast, combining FIT with the established calprotectin-based pathway achieved detection of all identified colorectal cancer and inflammatory bowel disease cases within the cohort. The integrated strategy also demonstrated strong discriminatory triage capability, appropriately directing most patients toward either colorectal cancer or inflammatory bowel disease referral pathways. These findings are clinically significant because diagnostic ambiguity in younger adults frequently leads to delayed IBD diagnosis, repeated consultations and inefficient use of endoscopic resources. The study additionally addresses a growing epidemiologic challenge: the rising incidence of both early-onset colorectal cancer and inflammatory bowel disease worldwide. The results reinforce the complementary biologic roles of FIT and calprotectin. FIT primarily reflects mucosal bleeding, whereas calprotectin captures neutrophil-mediated intestinal inflammation, allowing improved differentiation between inflammatory and neoplastic pathology. Clinically, this combined biomarker strategy may help refine referral pathways in primary care, reducing unnecessary urgent cancer referrals while simultaneously minimizing missed inflammatory bowel disease. The work is particularly relevant in healthcare systems facing increasing endoscopy demand and diagnostic pathway congestion. Better pre-endoscopic risk stratification could improve resource allocation and reduce diagnostic delay. The findings also support a broader shift toward multimarker diagnostic algorithms rather than reliance on single stool biomarkers for lower gastrointestinal symptom evaluation. Importantly, the study demonstrates that biomarker interpretation should be contextualized by patient age and disease prevalence, as diagnostic test performance varies substantially across populations. Limitations include the pilot nature of the study, relatively low colorectal cancer event numbers and the need for larger validation cohorts before broad implementation. Future work will likely focus on integrated biomarker-based referral models incorporating FIT, calprotectin, symptom phenotyping and potentially emerging molecular stool biomarkers. Overall, this study suggests that combining FIT with faecal calprotectin may substantially improve discriminatory referral pathways for younger adults with lower gastrointestinal symptoms, enhancing early detection of both colorectal cancer and inflammatory bowel disease while reducing diagnostic uncertainty.

Upadacitinib–Vedolizumab Combination Breaks the UC Efficacy Ceiling : Gastroenterology | May 2026

Introduction Ulcerative Colitis treatment outcomes remain constrained by an “efficacy ceiling,” with most advanced therapies achieving endoscopic remission rates below 30%. Rapid induction of deep remission remains a major unmet need, particularly in patients with moderate-to-severe disease. Problem Statement Whether short-term combination induction using a biologic and a selective JAK inhibitor can improve early endoscopic remission beyond current monotherapy standards in ulcerative colitis remains uncertain. Summary This prospective multicenter randomized trial evaluated an induction strategy combining Upadacitinib with Vedolizumab in patients with moderate-to-severe ulcerative colitis. Patients receiving combination induction achieved markedly higher rates of endoscopic remission at week 8 compared with vedolizumab monotherapy. Importantly, the study used stringent remission criteria requiring complete endoscopic normalization, strengthening the clinical significance of the findings. Clinical remission and histologic-endoscopic mucosal improvement were also substantially higher with combination therapy, suggesting that the benefits extended beyond symptomatic response to include deeper biologic disease control. One of the most clinically relevant observations was the rapidity of response. The addition of upadacitinib likely compensated for the slower onset traditionally associated with vedolizumab, potentially creating a synergistic induction strategy that combines rapid anti-inflammatory activity with gut-selective maintenance therapy. The study therefore introduces an important conceptual shift in inflammatory bowel disease management: short-term “bridging” combination therapy designed to rapidly induce deep remission while transitioning toward safer long-term biologic maintenance. Safety findings were reassuring, with adverse event rates comparable between groups and no serious adverse events observed during the short induction period. However, the authors appropriately caution that the sample size and limited follow-up duration restrict definitive safety conclusions. The trial is especially important because randomized evidence supporting combination advanced therapy in ulcerative colitis remains extremely limited. Most existing combination data derive from retrospective cohorts or refractory salvage settings. Mechanistically, the therapeutic rationale is compelling. Upadacitinib provides rapid intracellular cytokine suppression through JAK1 inhibition, whereas vedolizumab selectively inhibits gut lymphocyte trafficking. Together, these therapies may target complementary inflammatory pathways during the critical early induction phase. The findings also align with broader trends toward precision and stratified inflammatory bowel disease care, where aggressive early disease control may alter long-term outcomes including corticosteroid exposure, hospitalization and colectomy risk. Nevertheless, several limitations remain important. The trial was open-label, relatively small and terminated early, requiring cautious interpretation before widespread adoption into routine practice. Longer-term durability also remains unknown, particularly after withdrawal of upadacitinib and continuation with vedolizumab monotherapy alone. Future studies will need to clarify maintenance outcomes, relapse rates and optimal de-escalation strategies. The study additionally raises important questions regarding positioning of dual-targeted therapy within current treatment algorithms. Combination induction may ultimately prove particularly useful in patients with high inflammatory burden, prior biologic failure or those requiring rapid disease control. Overall, this randomized trial provides the first prospective evidence that short-term combination induction using upadacitinib and vedolizumab can significantly improve early endoscopic and clinical remission rates in moderate-to-severe ulcerative colitis, potentially overcoming the long-recognized efficacy ceiling of current monotherapy approaches.

AI and Multi-Omics Redefine Postoperative Crohn’s Recurrence : Gut | May 2026

Introduction Crohn's Disease postoperative recurrence remains one of the greatest long-term challenges after intestinal resection, with endoscopic recurrence developing in a substantial proportion of patients within the first postoperative year. Despite advances in biologic therapy and surgical techniques, accurate prediction and individualized monitoring of postoperative recurrence remain limited. Problem Statement Current postoperative surveillance strategies for Crohn’s disease rely largely on ileocolonoscopy and fecal biomarkers, both of which have important limitations in sensitivity, standardization and early risk prediction, restricting the development of precision postoperative management. Summary This state-of-the-art review outlines how artificial intelligence-enabled imaging and multi-omics technologies may fundamentally transform postoperative recurrence management in Crohn’s disease. The authors emphasize that postoperative recurrence is biologically heterogeneous and influenced by complex interactions among immune pathways, microbial ecology, genetics, surgical technique and environmental exposures. Traditional surveillance approaches struggle to fully capture this multidimensional disease behavior. Current postoperative monitoring is still dominated by ileocolonoscopy and Rutgeerts scoring, yet important limitations persist, including interobserver variability, uncertain applicability across newer anastomotic techniques and imperfect correlation with transmural disease activity. The review highlights major advances in high-resolution endoscopic technologies including confocal laser endomicroscopy and endocytoscopy. These techniques enable real-time microscopic assessment of the anastomosis and mucosal barrier, potentially allowing detection of early inflammatory and structural alterations before overt endoscopic recurrence becomes apparent. Simultaneously, non-invasive imaging modalities are rapidly evolving. Intestinal Ultrasound and cross-sectional imaging now permit dynamic transmural assessment, offering opportunities for serial postoperative monitoring without repeated invasive procedures. Beyond imaging, the review strongly emphasizes the growing role of multi-omics technologies. Genomics, transcriptomics, proteomics, metabolomics and microbiome profiling are increasingly uncovering biologic signatures associated with recurrence risk, immune activation and fibrotic progression. These technologies are revealing that postoperative recurrence likely represents multiple biologically distinct phenotypes rather than a single uniform process. Such insights may eventually support personalized postoperative therapeutic strategies rather than current generalized treatment algorithms. A particularly important theme is the integration of multimodal data through artificial intelligence. AI-driven models may combine clinical features, imaging findings, endoscopic characteristics and omics-derived biomarkers into predictive platforms capable of individualized recurrence forecasting. The authors propose that AI-enabled systems could eventually facilitate precision risk stratification, optimize surveillance timing and guide earlier therapeutic escalation in high-risk patients while avoiding overtreatment in lower-risk individuals. Importantly, the review maintains a balanced perspective regarding current limitations. Most emerging technologies still require prospective validation, standardized acquisition protocols and integration into real-world clinical workflows before widespread implementation. The article also underscores the need for harmonization of postoperative recurrence definitions and imaging endpoints across studies. Standardization will be essential for developing reproducible AI algorithms and clinically meaningful predictive models. From a translational standpoint, this review reflects the broader evolution of inflammatory bowel disease care toward precision medicine. Future postoperative management may increasingly rely on integrated biologic and imaging signatures rather than isolated endoscopic findings alone. The review additionally highlights how technological innovation is reshaping multidisciplinary Crohn’s disease care, requiring closer collaboration between gastroenterologists, colorectal surgeons, radiologists, computational scientists and molecular biologists. Overall, this review presents a compelling vision of future postoperative Crohn’s disease management in which AI-enabled imaging and multi-omics platforms drive earlier detection, individualized surveillance and biologically tailored therapeutic decision-making.

International Consensus Defines the Role of Intestinal Ultrasound in Postoperative Crohn’s Disease Surveillance : Lancet Gastroenterol Hepatol | May 2026

Introduction Crohn's Disease recurrence after ileocolic resection remains common, with postoperative endoscopic recurrence often preceding clinical symptoms. Early identification of recurrence is critical because timely therapeutic escalation may prevent progression to stricturing disease, repeat surgery and irreversible bowel damage. Although ileocolonoscopy remains the reference standard, increasing interest has emerged around Intestinal Ultrasound as a non-invasive, repeatable and patient-friendly monitoring tool. Problem Statement Despite growing clinical adoption of intestinal ultrasound in inflammatory bowel disease, there has been no international consensus regarding standardized implementation, interpretation and timing of ultrasound assessment for postoperative Crohn’s disease recurrence. Summary This international multidisciplinary RAND/UCLA appropriateness study established expert consensus recommendations for the use of intestinal ultrasound in detecting and evaluating postoperative recurrence after ileocolic resection in Crohn’s disease. The recommendations were developed through a rigorous consensus methodology incorporating systematic literature review, iterative expert voting and multidisciplinary ratification involving gastroenterologists, colorectal surgeons and radiologists from multiple countries. The resulting framework represents one of the most comprehensive attempts to standardize postoperative intestinal ultrasound assessment in Crohn’s disease. The panel identified several key anatomic regions that should routinely be evaluated during postoperative sonographic assessment. Particular emphasis was placed on detailed examination of the neoterminal ileum and the inlet of the neoterminal ileum, which were considered the sites most likely to reflect clinically meaningful postoperative recurrence. Additional evaluation of the blind limbs of the anastomosis, distal colonic segments and surrounding mesentery was also recommended. Importantly, the consensus expanded assessment beyond bowel wall thickness alone. Recommended sonographic parameters included bowel wall stratification, vascularity, mesenteric inflammatory fat, lymphadenopathy, luminal narrowing and detection of penetrating or stricturing complications such as abscesses, fistulas and prestenotic dilation. This reflects the increasingly sophisticated role of intestinal ultrasound as a comprehensive transmural disease assessment tool rather than merely a surrogate for mucosal inflammation. The panel also addressed timing of surveillance. Intestinal ultrasound was not recommended within the first four postoperative weeks because early inflammatory and healing-related changes may confound interpretation. Instead, the first formal postoperative assessment was recommended between 3 and 12 months after surgery, aligning with the biologic window during which early recurrence commonly develops. A particularly important aspect of the recommendations is the recognition of mesenteric assessment as a core component of postoperative surveillance. Increasing evidence suggests that mesenteric inflammation and creeping fat are integral drivers of Crohn’s disease progression, and intestinal ultrasound uniquely allows simultaneous bowel and mesenteric evaluation in real time. Clinically, these recommendations may substantially expand adoption of ultrasound-driven postoperative monitoring pathways. Compared with ileocolonoscopy, intestinal ultrasound offers several practical advantages including absence of sedation, lack of bowel preparation, repeatability, lower procedural burden and potential for point-of-care assessment during routine clinic visits. The study also reflects the broader paradigm shift within inflammatory bowel disease toward transmural monitoring. While endoscopy remains essential, cross-sectional modalities increasingly provide complementary information regarding deep tissue inflammation, fibrosis and penetrating complications that are not fully captured by mucosal visualization alone. Importantly, the panel emphasized that development of validated postoperative ultrasound indices remains a major unmet need. Standardized scoring systems integrating bowel wall thickness, vascularity and mesenteric findings will likely be essential for future clinical trial integration and treat-to-target strategies. Overall, this multidisciplinary international consensus establishes a standardized framework for intestinal ultrasound assessment of postoperative Crohn’s disease recurrence. The recommendations support intestinal ultrasound as an increasingly important non-invasive monitoring modality and provide critical groundwork for future validation studies and precision postoperative surveillance strategies in Crohn’s disease.

Real-World Risankizumab Outcomes in Refractory CD : Frontline Gastroenterol | May 2026

Introduction Risankizumab is a selective interleukin-23 p19 inhibitor approved for moderate-to-severe Crohn’s Disease following strong efficacy signals in phase III trials. However, real-world evidence in heavily pretreated Crohn’s disease populations, particularly after prior biologic and ustekinumab exposure, remains limited. This large multicentre UK cohort evaluated the effectiveness, persistence and safety of risankizumab across routine clinical practice. Problem Statement Many patients with Crohn’s disease experience failure of multiple advanced therapies, including anti-TNF agents and ustekinumab, creating substantial therapeutic challenges. Whether selective IL-23 p19 inhibition remains effective after prior IL-12/23 blockade in real-world refractory populations has remained uncertain. Summary This retrospective multicentre study included 763 patients treated across 25 UK health boards, representing one of the largest real-world risankizumab cohorts reported to date. The population was highly treatment refractory, with 92% previously exposed to anti-TNF therapy, 72% previously treated with ustekinumab and a median of three prior advanced therapy exposures. More than half had prior luminal surgery and 16% had a stoma at treatment initiation, underscoring the severe disease burden of the cohort. Despite this complexity, risankizumab demonstrated remarkably high treatment persistence, reaching 97.8% at 3 months, 95.4% at 6 months and 89.2% at 12 months. Persistence remained robust even among patients previously exposed to ustekinumab, suggesting that selective IL-23 p19 inhibition may retain efficacy despite prior IL-12/23 blockade. Prednisolone use at treatment initiation was the only significant predictor of reduced persistence, likely reflecting higher inflammatory burden and more refractory disease. Clinical and biochemical outcomes were similarly encouraging. Steroid-free clinical remission occurred in 59% at 3 months, 52% at 6 months and 50% at 12 months. CRP remission rates exceeded 50% throughout follow-up, while faecal calprotectin remission rates reached 44% at both 6 and 12 months. Significant improvements in Harvey-Bradshaw Index, inflammatory biomarkers, abdominal pain and stool frequency were observed across treatment intervals. Importantly, remission rates were largely comparable between ustekinumab-naïve and ustekinumab-exposed patients, supporting the mechanistic distinction between IL-23 p19 blockade and p40 inhibition. The study additionally provided important real-world insights into perianal disease. Among patients with active perianal Crohn’s disease, approximately one-third achieved clinical perianal response by 12 weeks, while most avoided new perianal complications during follow-up. These findings support a potential role for risankizumab in fistulising disease, although dedicated prospective studies remain necessary. Safety outcomes were favourable overall. Adverse events occurred in 17% of patients, though many reflected disease-related hospitalisations rather than drug toxicity. Serious infections requiring hospitalisation were infrequent, and discontinuation due to adverse effects remained uncommon. The overall safety profile aligned closely with phase III trial experience and previously published smaller real-world cohorts. Overall, this large UK real-world analysis confirms that risankizumab is highly effective and durable in medically refractory Crohn’s disease, including patients with multiple prior biologic failures and previous ustekinumab exposure. The findings reinforce IL-23 p19 inhibition as an important therapeutic mechanism in advanced Crohn’s disease and support its expanding integration into complex IBD treatment algorithms.

Upadacitinib Shows Real-World Benefit in Perianal Crohn’s Disease : Clin Gastroenterol Hepatol | May 2026

Introduction Perianal Crohn’s Disease remains one of the most disabling and treatment-refractory manifestations of inflammatory bowel disease, frequently associated with fistulas, abscesses, recurrent surgery and impaired quality of life. Although anti-TNF therapy has historically been the cornerstone of fistulizing disease management, many patients experience incomplete response or secondary loss of efficacy. Upadacitinib has demonstrated efficacy in luminal Crohn’s disease, and post-hoc analyses from phase III trials suggested potential benefit in perianal disease, but real-world data—particularly radiologic outcomes—have been limited. Problem Statement Management of perianal Crohn’s disease remains challenging, especially in patients with prior biologic exposure and longstanding fistulizing disease. Whether upadacitinib can achieve meaningful fistula healing and radiologic improvement in routine clinical practice has not been well established. Summary This multicenter North American retrospective cohort study evaluated 125 adults with active perianal Crohn’s disease treated with upadacitinib across 10 tertiary centers. The cohort represented a highly refractory population, with nearly half having complex fistulas and more than three-quarters previously exposed to anti-TNF therapy. Clinical outcomes were assessed using the Perianal Disease Activity Index (PDAI), alongside inflammatory biomarkers and pelvic MRI findings. Upadacitinib demonstrated clinically meaningful effectiveness in this difficult-to-treat population. Approximately 46% of patients achieved clinical response, while nearly 40% achieved clinical remission. Importantly, radiologic improvement was documented in more than half of patients undergoing pelvic MRI assessment, and complete radiologic healing occurred in approximately 12%, representing one of the first real-world MRI-based evaluations of upadacitinib in fistulizing Crohn’s disease. Rates of hospitalization and perianal surgery during follow-up remained relatively low, supporting meaningful disease control in routine practice. Treatment effectiveness appeared strongly influenced by prior biologic exposure and disease chronicity. Anti-TNF–naïve patients achieved substantially higher clinical response rates compared with previously exposed individuals, suggesting greater efficacy earlier in the disease course. Similarly, shorter perianal disease duration was associated with improved outcomes, reinforcing the concept that early aggressive intervention may improve fistula healing potential before irreversible fibrotic remodeling develops. Multivariable analysis identified prior anti-TNF exposure as a significant negative predictor of response. Overall, this study provides important real-world evidence supporting upadacitinib as a therapeutic option for perianal Crohn’s disease, particularly in patients with earlier disease and limited biologic exposure. The inclusion of radiologic outcomes strengthens the clinical relevance of the findings and supports further prospective controlled studies evaluating JAK inhibition for fistulizing Crohn’s disease management.

FIT Pathways Frequently Identify IBD in Younger Patients : Br J Surg | May 2026

Introduction Inflammatory bowel disease and Colorectal Cancer frequently present with overlapping lower gastrointestinal symptoms including rectal bleeding, altered bowel habits and abdominal pain. In the UK, symptomatic Faecal immunochemical testing is widely used in primary care to triage patients suspected of colorectal cancer. However, the extent to which FIT pathways also identify IBD, particularly in younger adults, has remained poorly characterized. Problem Statement Current FIT-based referral pathways are primarily optimized for colorectal cancer detection and may insufficiently account for inflammatory bowel disease risk. Whether combining FIT with faecal calprotectin (FCP) could improve diagnostic stratification for younger symptomatic patients remains uncertain. Summary This large population-based cohort study analyzed more than 473,000 symptomatic patients undergoing FIT testing in UK primary care between 2019 and 2023. Within one year of FIT testing, nearly 2,800 patients were diagnosed with IBD. Importantly, individuals younger than 50 years accounted for more than half of all IBD diagnoses but less than 7% of colorectal cancer diagnoses, highlighting a major age-related shift in disease probability within symptomatic FIT pathways. Elevated FIT levels were strongly associated with increased IBD risk, with a markedly higher incidence observed among patients with FIT ≥10 µg Hb/g. The highest-risk subgroup comprised younger patients with both elevated FIT and elevated faecal calprotectin, where the probability of IBD exceeded 20%. Conversely, a normal FCP substantially reduced combined CRC/IBD risk even in patients with elevated FIT, suggesting important negative predictive value for inflammatory disease exclusion. These findings suggest that IBD may be a more likely diagnosis than colorectal cancer in younger symptomatic individuals referred through FIT pathways. The study supports incorporation of routine faecal calprotectin testing alongside FIT to improve diagnostic precision, prioritize endoscopic evaluation and potentially reduce unnecessary invasive investigations in low-risk patients. Overall, the data reinforce the evolving role of combined stool biomarker strategies in modern lower gastrointestinal triage algorithms and emphasize the importance of age-specific interpretation of symptomatic FIT results.