Trending Topics in Gastroenterology | GastroAGI

IBD Across Ethnicities: Gastroenterology | July 2026

Introduction: The global incidence of inflammatory bowel disease (IBD) continues to rise, particularly in newly industrialized countries. This comprehensive systematic review evaluated how race, ethnicity, geography, and migration influence the clinical phenotype and outcomes of Crohn's disease (CD) and ulcerative colitis (UC). Why was this study needed? • The global epidemiology of IBD is rapidly evolving. • The influence of ethnicity and geography on disease phenotype remains incompletely understood. • Migration may alter disease risk and clinical presentation. • Understanding phenotypic differences is essential for personalized IBD care. • Large global population-based data have been lacking. Results: • Crohn's disease showed significant ethnic differences, with Asian patients having the highest prevalence of perianal disease, whereas ulcerative colitis demonstrated fewer phenotypic differences across ethnic groups. • Family history of IBD varied substantially, being more common among Middle Eastern populations and Asian immigrants than native Asian populations, suggesting an interaction between genetics and environmental exposure. • Persistent differences in sex distribution, disease phenotype, and clinical presentation across racial and geographic populations indicate that IBD is not a uniform global disease. Clinical Impact: This landmark meta-analysis demonstrates that ethnicity, geography, and migration significantly influence the clinical expression of IBD, particularly Crohn's disease. These findings support the development of personalized risk assessment, surveillance strategies, and precision medicine, while emphasizing the need for future multi-omics research in diverse populations. Bottom Line: IBD is a heterogeneous global disease shaped by genetics, environment, and migration. Recognizing ethnic and geographic differences in disease phenotype is essential for improving diagnosis, individualized management, and future precision medicine approaches.

Moving Beyond the "Wait to Fail" Strategy in ASUC: FG | 2026

Introduction: Acute severe ulcerative colitis (ASUC) remains one of the most life-threatening emergencies in inflammatory bowel disease. Despite advances in IBD therapy, first-line management has changed little over the past two decades, and colectomy continues to be required in a substantial proportion of patients. This review highlights emerging strategies aimed at personalizing treatment and improving outcomes. Why was this review needed? • Management of ASUC has remained largely unchanged for nearly 20 years. • One-third of patients fail intravenous corticosteroid therapy. • Colectomy and mortality remain significant despite current treatment. • Early identification of steroid non-responders remains challenging. • Personalized treatment strategies are needed to improve outcomes. Key Takeaways: • Intravenous corticosteroids remain the first-line therapy, while infliximab and ciclosporin are the only rescue therapies supported by robust randomized trial evidence. • Up to one-third of patients fail steroid therapy, requiring early rescue treatment or surgery. • Colectomy remains necessary in 10–15% of patients during the initial admission, with the risk increasing after subsequent hospitalizations. • JAK inhibitors are emerging as promising rescue therapies, although larger prospective trials are still required. • Pharmacokinetic-guided infliximab dosing may optimize treatment response in selected patients. • Risk prediction tools, such as ADMIT-ASC, may help identify high-risk patients early and facilitate individualized treatment decisions. • Future management is expected to shift from a uniform "wait-to-fail" approach toward early risk stratification and precision medicine. Clinical Impact: The future management of ASUC is likely to focus on earlier identification of high-risk patients, individualized rescue therapy, and optimized biologic dosing rather than waiting for treatment failure. This strategy has the potential to reduce colectomy rates and improve long-term outcomes. Bottom Line: Acute severe ulcerative colitis remains a medical emergency with substantial morbidity. The next major advance will be personalized, risk-based treatment, integrating predictive models, optimized biologic therapy, and novel agents such as JAK inhibitors to improve patient outcomes.

FMT in Ulcerative Colitis: JGH | July 2026

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising global burden. Although current therapies are effective, many patients fail treatment or experience adverse effects. Fecal microbiota transplantation (FMT) has emerged as a promising microbiome-based therapy aimed at restoring gut microbial balance and immune homeostasis. Why was this article needed? • Previous FMT studies showed encouraging but inconsistent results. • Optimal donor selection, delivery route, and treatment protocols remain unclear. • Long-term safety and durability of response require further evaluation. • Recent randomized controlled trials warranted an updated meta-analysis. • The study also assessed whether multi-donor FMT and oral capsule therapy improve outcomes. Results: • FMT significantly improved both clinical symptoms and endoscopic remission, confirming its superiority over placebo in active UC. • FMT demonstrated a favorable short-term safety profile, with adverse events comparable to placebo. • Multi-donor FMT and oral capsule delivery emerged as the most promising strategies, although standardized protocols and long-term data are still needed. Clinical Impact: This updated meta-analysis strengthens the evidence supporting FMT as an effective and safe option for inducing remission in UC. Although it remains investigational in routine practice, FMT is emerging as one of the most promising microbiome-based therapies for selected patients. Bottom Line: FMT is an effective microbiome-based therapy for inducing remission in ulcerative colitis. Multi-donor FMT and oral capsule delivery appear particularly promising, but larger long-term trials are needed before widespread clinical adoption.

Engineering Immune Cell Therapies for IBD: Nat Re Gastroe & Hepato | June 2026

Introduction: Despite major advances with biologics and small molecules, many patients with IBD continue to have refractory disease or lose treatment response. This Perspective explores engineered cellular therapies designed to restore immune tolerance rather than simply suppress inflammation. Why was this article needed? Current therapies effectively control inflammation but rarely correct the underlying immune dysfunction. Cellular immunotherapy offers the potential for durable remission through immune reprogramming. • Stem Cell Therapy: Haematopoietic and mesenchymal stem cells have shown encouraging results in refractory IBD by promoting immune regulation and tissue repair. However, larger clinical trials are needed to establish long-term safety and efficacy. • Regulatory T-Cell Therapy: Engineered regulatory T (Treg) cells aim to restore immune tolerance through targeted anti-inflammatory effects rather than broad immunosuppression. Early clinical trials are evaluating their safety and therapeutic potential. • Tr1 Cell Therapy: IL-10-producing type 1 regulatory T (Tr1) cells may suppress intestinal inflammation and promote long-term immune regulation. Early-stage clinical studies are currently in progress. • CAR T-Cell Therapy: A recent case report demonstrated sustained remission of ulcerative colitis following CD19-targeted CAR T-cell therapy, suggesting an important pathogenic role for B cells and opening a promising new therapeutic strategy. • CAR Treg Therapy: CAR Treg cells combine antigen-specific targeting with immune regulation, providing precise control of intestinal inflammation while preserving normal immune function. Clinical Impact: Engineered cellular therapies could transform the management of refractory IBD, particularly in patients with multiple biologic failures. However, these therapies remain investigational and require validation in well-designed prospective clinical trials. Bottom Line: Stem cells, Tregs, Tr1 cells, and CAR T-cell platforms represent the next generation of IBD therapy, with the potential to restore immune tolerance and achieve durable disease modification beyond conventional immunosuppression.

Real-World IBD Patients Rarely Meet Clinical Trial Criteria: AJG | June 2026

Introduction: Randomized clinical trials (RCTs) are the cornerstone for approving biologic therapies in inflammatory bowel disease (IBD). However, strict eligibility criteria may exclude many patients encountered in routine clinical practice, raising concerns about the real-world applicability of trial results. Why was this study needed? The external validity of pivotal IBD clinical trials has not been well established. This study evaluated how many real-world patients would have qualified for landmark biologic trials and whether trial eligibility influenced treatment outcomes. What did the study show? • Only 16.9% of patients met eligibility criteria for pivotal biologic RCTs, falling to 8% using newer trial criteria. • Disease-related exclusion criteria accounted for most ineligible patients. • Patients with ulcerative colitis were significantly less likely to qualify for RCTs than those with Crohn's disease. • Clinical response and remission rates were similar in trial-eligible and non-eligible patients. • Adverse events and drug discontinuation rates did not differ between the two groups. • Long-term treatment persistence was also comparable regardless of trial eligibility. Clinical Impact: These findings suggest that biologic therapies remain effective and safe in many patients who would have been excluded from clinical trials. Real-world evidence should complement RCT data when making treatment decisions and developing future clinical guidelines. Take-Home Message: Most patients treated with biologics for IBD would not qualify for pivotal clinical trials. Despite this, real-world effectiveness, safety, and treatment persistence are comparable, emphasizing that clinical judgment and real-world evidence are essential alongside randomized trial data.

Mirikizumab in Ulcerative Colitis: JCC | June 2026

Introduction: Mirikizumab, a selective IL-23p19 inhibitor, has demonstrated efficacy in phase III clinical trials for moderate-to-severe ulcerative colitis (UC). This multicenter Italian real-world study evaluated its effectiveness and safety in routine clinical practice, including patients previously exposed to multiple biologic therapies. Why was this study needed? Randomized trials often exclude complex patients with prior biologic failures and multiple comorbidities. Real-world data are essential to determine whether mirikizumab performs similarly in everyday clinical practice. What did the study show? • Nearly half of the patients achieved steroid-free clinical remission within 12 weeks. • More than 60% achieved a meaningful clinical response after induction therapy. • Clinical effectiveness was comparable in biologic-naïve and biologic-experienced patients. • Prior ustekinumab exposure did not significantly reduce treatment effectiveness, although remission rates tended to be lower. • Patients requiring extended induction had lower remission rates, suggesting more difficult-to-treat disease. • Biochemical improvement in CRP and fecal calprotectin did not reach statistical significance during early follow-up. • Mirikizumab demonstrated an excellent safety profile, with no treatment-related adverse events reported and only three patients discontinuing therapy because of lack of efficacy. Clinical Impact: These findings reinforce mirikizumab as an effective treatment option for moderate-to-severe UC in routine clinical practice, including patients with previous biologic exposure. The favorable safety profile and consistent clinical response support its use across a broad spectrum of patients. Take-Home Message: This real-world multicenter study confirms that mirikizumab is an effective and well-tolerated therapy for ulcerative colitis, achieving meaningful steroid-free remission even in biologic-experienced patients. These results support its growing role as an important IL-23–targeted treatment in everyday clinical practice.

Mirikizumab Shows Promising Real-World Effectiveness in Ulcerative Colitis: JCC | May 2026

Introduction: Mirikizumab, a selective IL-23p19 inhibitor, has demonstrated efficacy in phase III clinical trials for moderate-to-severe ulcerative colitis (UC). This multicenter Italian real-world study evaluated its effectiveness and safety in routine clinical practice, including patients previously exposed to multiple biologic therapies. Why was this study needed? Randomised trials often exclude complex patients with prior biologic failures and multiple comorbidities. Real-world data are essential to determine whether mirikizumab performs similarly in everyday clinical practice. What did the study show? • Nearly half of the patients achieved steroid-free clinical remission within 12 weeks. • More than 60% achieved a meaningful clinical response after induction therapy. • Clinical effectiveness was comparable in biologic-naïve and biologic-experienced patients. • Prior ustekinumab exposure did not significantly reduce treatment effectiveness, although remission rates tended to be lower. • Patients requiring extended induction had lower remission rates, suggesting more difficult-to-treat disease. • Biochemical improvement in CRP and fecal calprotectin did not reach statistical significance during early follow-up. • Mirikizumab demonstrated an excellent safety profile, with no treatment-related adverse events reported and only three patients discontinuing therapy because of lack of efficacy. Clinical Impact: These findings reinforce mirikizumab as an effective treatment option for moderate-to-severe UC in routine clinical practice, including patients with previous biologic exposure. The favorable safety profile and consistent clinical response support its use across a broad spectrum of patients. Take-Home Message: This real-world multicenter study confirms that mirikizumab is an effective and well-tolerated therapy for ulcerative colitis, achieving meaningful steroid-free remission even in biologic-experienced patients. These results support its growing role as an important IL-23–targeted treatment in everyday clinical practice.

Upadacitinib + Vedolizumab: CGH | June 2026

• This multicenter randomized trial evaluated whether combining upadacitinib with vedolizumab during induction therapy could improve outcomes in moderate-to-severe ulcerative colitis. • A total of 113 patients were randomized to receive either vedolizumab alone or vedolizumab plus upadacitinib for 8 weeks. • The rationale was to combine the rapid anti-inflammatory effect of a JAK inhibitor with the gut-selective mechanism and favorable long-term safety profile of vedolizumab. • The combination therapy significantly improved endoscopic remission rates. • At week 8, endoscopic remission was achieved in 37.5% of patients receiving combination therapy compared with 15.1% receiving vedolizumab alone. • Clinical remission was also substantially higher with combination treatment (65% vs 35.6%). • Histologic-endoscopic mucosal improvement, an increasingly important treatment target, was significantly more frequent in the combination arm. • These findings suggest that early dual-target therapy may help overcome the therapeutic ceiling traditionally observed with advanced monotherapy. • Importantly, short-term safety appeared reassuring. • Adverse events were uncommon and occurred at similar rates in both treatment groups. • No serious adverse events were reported during the 8-week induction period. • One patient discontinued combination therapy because of severe rash and elevated lipid levels. • The study supports the emerging concept of a “hit hard and heal early” approach in ulcerative colitis, aiming to achieve deep remission rapidly before transitioning to maintenance therapy. • Several limitations should be considered: Open-label design Early trial termination after interim benefit analysis Smaller sample size than originally planned No upadacitinib monotherapy arm • Ongoing 54-week follow-up will determine whether these impressive induction results translate into durable long-term remission and acceptable long-term safety. Bottom line: Short-term combination therapy with upadacitinib plus vedolizumab more than doubled endoscopic remission rates compared with vedolizumab alone in moderate-to-severe ulcerative colitis, suggesting a promising new induction strategy that now requires long-term validation.

Dose Escalation Offers Limited Benefit After Ustekinumab Failure : Gastroenterology | Jul 2026

Introduction: Ustekinumab is an established treatment for moderate-to-severe Crohn’s disease, but secondary loss of response remains a significant clinical challenge during long-term therapy. In routine practice, dose intensification strategies are frequently employed to recapture disease control, although high-quality prospective evidence supporting specific escalation approaches has been limited. Problem Statement: When patients lose response to ustekinumab maintenance therapy, clinicians often intensify treatment by shortening dosing intervals or administering intravenous reinduction. However, the optimal intensification strategy and its long-term effectiveness have remained uncertain, leading to substantial variability in clinical practice. Summary: The REScUE study is the first prospective randomized trial specifically evaluating ustekinumab dose-intensification strategies in Crohn’s disease patients experiencing secondary loss of response. Following intravenous reinduction, patients were assigned to either intensified subcutaneous dosing every four weeks or standard maintenance dosing every eight weeks. At 48 weeks, steroid-free clinical remission rates were low and did not differ significantly between the two treatment strategies. Likewise, safety outcomes were comparable, with similar rates of serious adverse events across both groups. These findings suggest that increasing the frequency of ustekinumab administration after intravenous reinduction does not provide additional clinical benefit compared with continuing standard eight-week maintenance dosing. The study challenges the common assumption that more intensive dosing necessarily improves outcomes in patients with secondary loss of response. Importantly, the overall modest remission rates observed indicate that many patients who lose response to ustekinumab may require alternative therapeutic approaches rather than further dose escalation. From a practical standpoint, the results support a more selective use of intensified ustekinumab schedules, potentially reducing treatment burden and healthcare costs without compromising efficacy. Overall, the REScUE trial provides important prospective evidence that routine escalation to four-week ustekinumab dosing after intravenous reinduction may not improve long-term outcomes in Crohn’s disease, highlighting the need for individualized treatment decisions and consideration of alternative therapeutic mechanisms when secondary loss of response occurs.

Subcutaneous Infliximab Achieves Higher Colonic Tissue Drug Levels Than Intravenous Therapy: UEG Journal | March 2026

• Infliximab exerts its therapeutic effect within intestinal tissue, yet most therapeutic drug monitoring currently relies on serum concentrations. • This study is the first to directly compare serum and colonic tissue infliximab concentrations between subcutaneous (SC) and intravenous (IV) infliximab in patients with IBD. • Patients receiving subcutaneous infliximab achieved significantly higher serum drug concentrations compared with those receiving intravenous therapy. • More importantly, colonic tissue infliximab concentrations were also significantly higher with subcutaneous administration, suggesting enhanced delivery to the therapeutic target organ. • Serum and tissue drug concentrations were positively correlated in both treatment groups, confirming that systemic exposure reflects, at least partially, mucosal drug availability. • Patients with higher colonic tissue infliximab concentrations experienced better clinical outcomes and were more likely to maintain sustained remission. • Colonic tissue drug levels demonstrated stronger predictive value for long-term remission than serum trough levels. • Tissue concentrations appeared highest in areas with mild-to-moderate inflammation, supporting the concept that active inflammatory tissue may facilitate local drug accumulation. • The findings provide a biological explanation for the favorable pharmacokinetic profile observed with subcutaneous infliximab in previous clinical studies. • The study raises an important concept: the true therapeutic target is the intestinal mucosa, not the bloodstream. • Current therapeutic drug monitoring strategies may therefore underestimate clinically relevant drug exposure when relying solely on serum concentrations. • Although tissue-based monitoring is not yet practical for routine clinical care, these data support future development of mucosal pharmacokinetic biomarkers. • The study also reinforces growing evidence that subcutaneous infliximab is not merely non-inferior to intravenous therapy but may offer pharmacologic advantages. • Larger prospective studies will be required to determine whether targeting tissue drug concentrations can further optimize treatment outcomes. Bottom line: Subcutaneous infliximab produces significantly higher serum and colonic tissue drug concentrations than intravenous infliximab. Colonic tissue drug levels correlate strongly with clinical remission and may represent the next frontier in therapeutic drug monitoring for IBD.