BACKGROUND AND AIMS:Inflammatory bowel disease (IBD) is emerging in the Asia-Pacific region including Malaysia. The aim of this study is to compare the current incidence and prevalence of IBD in Malaysia from the previous decade, as well as comparing the incidence rates between the urban and rural population. METHODS:Kinta Valley was selected as the urban catchment area while Hilir Perak was selected for the rural catchment area within the same state. Patients newly diagnosed with IBD were prospectively recruited, and all confirmed IBD cases were included for the prevalence analysis. Baseline demographic information and disease characteristics were recorded. RESULTS:The crude incidence rates of IBD, ulcerative colitis (UC), Crohn disease (CD) and IBD unclassified (IBD-U) in Kinta Valley were 1.13, 0.45, 0.60, and 0.08 per 100 000 person-years, respectively, compared to 0.68, 0.46, and 0.20 per 100 000 person-years in 2013. The incidence of UC:CD was 0.75:1 compared to 2.3:1 from the previous study. The prevalence rates were 15.08, 10.13, 4.84, and 0.11 for IBD, CD, UC, and IBD-U per 100 000 population, respectively. The matching incidence rates in a nearby rural area were higher, at 3.29, 1.88, 1.41, and 0.47 per 100 000 person-years, respectively, but the overall incident cases were very low. CONCLUSION:Our findings suggest an increasing incidence of IBD in Malaysia, in keeping with the second stage of the global evolution of IBD. There is a potential shift in the relative incidence of CD compared to UC, but larger population studies are required for confirmation.

Introduction The global rise in inflammatory bowel disease (IBD) parallels socio-economic development, but its influence on disease epidemiology and phenotype remains unclear. We aimed to characterise IBD incidence, clinical features, and associations with socio-economic indices across newly industrialised countries. Methods This prospective population-based study spanned 16 regions in Africa, Asia, Latin America, and the Middle East from October 2021 for one year. Poisson regression estimated incidence rate ratios (IRR) for Human Development Index (HDI), Socio-demographic Index (SDI), subnational HDI, and urban population percentage. Mixed-effects models examined associations with disease phenotype, activity, and treatment. Results Of 606 incident cases (229 Crohn’s disease [CD], 348 ulcerative colitis [UC], 29 IBD-unclassified), incidence varied widely. Hong Kong had the highest crude annual incidence (IBD 7.43; CD 2.69; UC 3.44) and Vietnam the lowest (0.13; 0.04; 0.08). Urban population (per 10% increase) was associated with higher incidence of IBD (IRR 1.68), CD (1.73), and UC (1.62). HDI and SDI significantly correlated with CD (IRR 4.05 and 2.96, respectively), but not subnational HDI. Higher HDI and subnational HDI were associated with increased odds of perianal CD (adjusted OR 2.61 and 2.40). Other disease phenotype, activity, and treatment pattern were not significantly linked to any index. Conclusion Higher urbanisation and development are associated with higher IBD incidence, particularly CD, but not with disease activity at diagnosis. Notably, perianal CD was more common in regions with higher HDI and subnational HDI, suggesting an association with regional socioeconomic development. These highlight the need for region-specific early diagnosis strategies.

BACKGROUND:Dietary interventions can serve as an alternative or adjunct to pharmacological intervention in inflammatory bowel disease (IBD). This study aimed to investigate various dietary beliefs, barriers and acceptability of diet among IBD patients. METHODS:A multicenter, cross-sectional survey was conducted across four Asia-Pacific countries. An anonymized online questionnaire was distributed through 10 participating IBD centers. Respondents rated the acceptability of IBD-related diets using a five-point Likert scale, with a score of 4 or more indicating acceptability. RESULTS:A total of 567 responses were received from 56.2% patients with Crohn's disease, and 42.5% with disease duration exceeding 10 years. While only 40.6% believed diet contributes to IBD causation, 80.2% avoided certain food during disease relapse. Respondents receiving advice from friends, family or acquaintances were more likely to avoid certain food during relapse (P < 0.01) and attempt therapeutic diets (P < 0.01) than those who were advised by healthcare professionals. Although many respondents modified diet during flares (46.4%), long term adherence remained low across most dietary patterns (24.4%). Key barriers included difficulties in meal preparation (46.0%) and social interference (42.9%). Respondents prioritized dietary effectiveness in symptom control (77.2%) and ease of meal preparation (69.6%). Low-fiber and Mediterranean diets were most acceptable, whereas exclusive enteral nutrition was least acceptable. CONCLUSION:Dietary choices are influenced by ease of preparation and social factors. A reliance on non-professional advice highlights an opportunity to strengthen clinician-patient communication around dietary modifications. Tailored, culturally sensitive dietary strategies may enhance adherence and acceptability in a diverse population, factors that are important when evaluating the role of dietary interventions in IBD management.

Ulcerative colitis (UC) and Crohn's disease (CD) are increasingly prevalent in the Asia Pacific region, necessitating updated, region-specific guidance on advanced therapies. Targeted small molecule agents, such as filgotinib, tofacitinib, upadacitinib, etrasimod, and ozanimod; and the IL-23 p19 inhibitors (guselkumab, mirikizumab, risankizumab) are the newest advanced therapies in our armamentarium for the treatment of IBD. The aim of the Asia-Pacific consensus statements is to provide context-specific recommendations integrating real-world evidence specific to our region. The Asian-Pacific Association of Gastroenterology (APAGE) Committee on Inflammatory Bowel Disease, with the participation of Asian Education Network in Inflammatory Bowel Disease (AEN-IBD), convened a forum of 34 IBD experts from 12 countries to develop consensus guidelines on the best practices on the use of these new advanced therapies using the modified Delphi method. IL-23 p19 inhibitors have shown good efficacy in biologic-naïve and experienced patients in both UC and CD, with clinical and endoscopic superiority over ustekinumab and an excellent safety profile. JAK inhibitors (tofacitinib and filgotinib) are efficacious in UC, and upadacitinib is efficacious in both UC and CD. They have a rapid time to response, and emerging data on acute severe UC appears promising. However, careful screening and monitoring is needed for known side effects, and prophylactic vaccination for herpes zoster should be considered. S1P modulators (ozanimod, etrasimod) are efficacious in UC with a favorable side effect profile.

BACKGROUND & AIMS:Primary sclerosing cholangitis (PSC) frequently coexists with inflammatory bowel disease (IBD). PSC is a progressive disease that may lead to end-stage liver failure requiring liver transplantation (LT). Although PSC-IBD has been extensively studied in Western populations, data from Asia remain limited. We conducted an international multicenter study across Asia to investigate the prevalence of PSC in IBD patients and evaluate its impact on clinical outcomes. METHODS:This retrospective cohort study included patients with IBD from 25 hospitals in 6 Asian countries. The primary endpoint was the prevalence of PSC in patients with IBD. The secondary endpoints included the incidence of colorectal neoplasia and IBD-related surgery following IBD diagnosis, and the occurrence of cholangiocarcinoma, LT, and death after PSC diagnosis among patients with PSC-IBD. Temporal trends were assessed across 5 diagnostic eras of PSC. RESULTS:Among 51,314 patients with IBD, 474 had PSC (0.92%), with a prevalence of 1.4% in ulcerative colitis and 0.13% in Crohn's disease. Among 375 Asian patients with PSC-IBD, 9.1% developed colorectal neoplasia, 7.2% developed cholangiocarcinoma, 24% underwent LT, and 16% died. In more recent diagnostic eras, patients presented with fewer symptoms, lower alkaline phosphatase levels, and better liver function scores. The use of magnetic resonance cholangiopancreatography has increased over time. Symptomatic PSC and low serum albumin were significantly associated with a shorter time to LT, which was significantly longer in recent eras (P = .016). CONCLUSIONS:PSC is less prevalent among Asian patients with IBD than in Western populations. The increased use of magnetic resonance cholangiopancreatography may enable earlier detection, contributing to milder disease severity and improved clinical outcomes in recent years. umin.ac.jp, Number UMIN000054487.

Background: Mucosal histological activity is increasingly valued as a treatment endpoint in inflammatory bowel diseases (IBD). In the Asia Pacific region, the utility and acceptability of IBD histology as a treatment endpoint are uncertain due to the heterogeneity of IBD prevalence, resourcing and level of knowledge among practitioners. There is an opportunity to engage clinicians to harmonise histology reporting and collaborate with pathologists in this field. Objectives: We aimed to develop consensus statements through anonymous voting on histological features, processing, reporting and relevance to treatment outcomes in IBD, including ulcerative colitis (UC) and Crohn’s disease (CD). Design: The consensus document was developed through a comprehensive literature review, followed by a deliberation process among experts in the field. Methods: Representatives of the Asia Pacific Association of Gastroenterology, in collaboration with pathologists, voted anonymously in accordance with modified Delphi methodology on statements relevant to IBD and histology. Domains of interest were histological features of UC and CD, relevance to clinical management and the potential utility of artificial intelligence (AI) in grading histological disease severity. Level of evidence and recommendation grade were included in accordance with the National Health and Medical Research Council, Australia guidelines of Australia. Results: Consensus was reached on 37 out of 38 statements concerning definitions, pathology processing and reporting, scoring system and relevance to clinical outcomes. Knowledge gaps were identified with uncertainty over the role of AI. Conclusion: These consensus statements provide recommendations, with specific relevance to the Asia Pacific region, on the role of histology in IBD to harmonise its use. The statements will promote understanding and applicability in research and in the routine management of IBD.

During the twentieth century, inflammatory bowel disease (IBD) was considered a disease of early industrialized regions in North America, Europe and Oceania1. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily2-4. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases. A fourth stage (prevalence equilibrium) has been proposed in which the prevalence slope plateaus due to demographic shifts in an ageing IBD population, but it has not yet been evidenced. To date, these stages have remained theoretical, lacking specific numerical indicators to define transition points. Here, using real-world data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920-2024), we show spatiotemporal transitions across stages 1-3 and model stage 4 progression. Understanding the evolution of IBD across epidemiologic stages enables healthcare systems to better anticipate the future worldwide burden of IBD.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Inflammatory bowel disease (IBD) is emerging in Asia, but there are many challenges in making the diagnosis. There is no gold standard for the diagnosis of IBD, which is often made based on a combination of clinical, endoscopic, radiological, and histological features, none of which are specific for the condition. Although there are many non-infectious mimics, such as Behcet's, drug-induced enterocolitis, and lymphoma, the main dilemma is differentiating IBD from infection; namely, Crohn's disease (CD) from intestinal tuberculosis (ITB). However, a careful history/examination, targeted investigations, along with histopathology should make it possible to make a definitive diagnosis of IBD in the majority of cases. In cases where the diagnosis is still unclear, empirical treatment based on the most likely diagnosis can be started, but careful reassessment is essential.

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn. image

BackgroundATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.ObjectivesTo perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.MethodsLiterature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP) and 95% CI were calculated under the random effects model.ResultsOur analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP: 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP: 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP: 1.21, 95% CI: 1.07-1.38, p-value: 0.003).ConclusionsATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary. image

BACKGROUND:Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS:We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS:We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS:The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION:6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

Abstract BACKGROUND Epidemiologic stages of inflammatory bowel disease (IBD) have been proposed: 1. Emergence (low incidence and prevalence); 2. Acceleration in Incidence (rapidly rising incidence, low prevalence); and 3. Compounding Prevalence (stabilizing incidence, rapidly rising prevalence). To date, these stages have been theoretical without quantified definitions of incidence and prevalence. AIM To use machine learning to determine incidence and prevalence ranges corresponding to the epidemiologic stages and provide stage classifications across time for global regions. METHODS We built a supervised random forest classifier in R to determine epidemiologic stages of IBD from population-based studies (n=340), a subset derived from a systematic review on the incidence and prevalence of IBD. A labelled training data set comprising rates of incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) extracted from the systematic review was used to predict classifications of stage 1, stage 2, or stage 3 for each region, stratified by decade (1960–2019). Model accuracy was measured using a blind validation data set. The validated model was then used to predict stage classifications for regions in the data set. Interquartile ranges for incidence and prevalence of CD and UC were calculated on the random forest output, and the distributions were compared using negative binomial regression. RESULTS The random forest’s classification accuracy on the blinded validation data was 93.7% (95%CI: 90.6, 96.1) indicating an appropriate model fit and performance. Significant differences between all stages for the incidence and prevalence of CD and UC (p<0.001) were found. The clear distinction across stages defines the incidence and prevalence ranges (25th–75th, per 100,000) for IBD as: CD incidence 0.0–0.3, UC incidence 0.2–0.7, CD prevalence 0.3–2.2, and UC prevalence 1.7–8.1 for stage 1; CD incidence 1.0–4.4, UC incidence 2.3–6.3, CD prevalence 9.0–33.9, and UC prevalence 22.8–73.3 for stage 2; and CD incidence 6.6–14.0, UC incidence 10.1–18.1, CD prevalence 163.2–274.7, and UC prevalence 189.1–323.2 for stage 3 (Figure 1). A decade-by-decade analysis shows global regions transitioning across the epidemiologic stages (Figure 2). By the 2010s, North America, Scandinavia, Western Europe, Australia, and New Zealand were in stage 3. Most regions in Asia and Latin America were in stage 1 in the last half of the 20th century, with many transitioning to stage 2 in the 2010s. DISCUSSION Temporal incidence and prevalence data show that regions transition across epidemiologic stages. Numerical definitions of the epidemiologic stages can be used to establish the anticipated burden growth of IBD by providing estimated rates of the number of incident and prevalent IBD cases a region can expect as it transitions between IBD epidemiologic stages in the future. Figure 1 Coalescing ranges for incidence (panel A) and prevalence (panel B) by Crohn’s disease and ulcerative colitis at epidemiologic stage 1, stage 2, and stage 3. Data were categorized by data type (incidence or prevalence), disease type (Crohn’s disease or ulcerative colitis), and epidemiologic stage, as per results from the random forest classifier. The 25th and 75th percentiles were calculated using the rates across all regions included in the analysis for all available time points for each box group. Figure 2 Global maps depicting epidemiologic stages of IBD evolution from 1960 to 2019 broken down by decade, as predicted by the random forest model. Panel A contains stage classifications from 1960 to 1969; panel B contains stage classifications from 1970 to 1979; panel C contains stage classifications from 1980 to 1989; panel D contains stage classifications from 1990 to 1999; panel E contains stage classifications from 2000 to 2009; and panel F contains stage classifications from 2010 to 2019.

Despite the advancements in medical therapy, Crohn's disease (CD) remains an unpredictable disease with a significant proportion of patients developing complications such as stricture, fistula, or even perforation requiring surgical intervention. In particular, stricturing CD remains a significant problem with approximately 50% of CD patients developing a stricture in their lifetime.1 The pathogenesis of stricturing disease in CD is complex involving inflammatory-dependent and independent mechanisms.1 Some patients are asymptomatic, but most will have some form of acute or chronic obstructive symptoms. Patients with acute obstruction usually present with acute abdominal pain, distension, and vomiting while patients with chronic obstruction presents with low-grade abdominal discomfort, postprandial abdominal cramps, distension, borborygmi, and weight loss. Strictures in CD have classically been divided into inflammatory or fibrotic, but in reality, most strictures are a combination of both. The differentiation between predominantly inflammatory and fibrotic strictures is made using a combination of clinical assessment, inflammatory biomarkers, endoscopy, and cross-sectional imaging such as intestinal ultrasound, magnetic resonance imaging, or computed tomography (CT) enterography. Studies have shown that use of biologic therapy can prevent or at least delay the development or progression of strictures,2-5 but are effective only in inflammatory dominant strictures. As a result, an endoscopic or surgical approach is often required in patients with fibrostenotic strictures. Surgery (bowel resection or stricturoplasty) is considered the "definitive" treatment but many of these patients are on immunosuppressive medication and malnourished; with a significant risk of developing postoperative complications. In addition, surgery cannot also be considered definitive as the recurrence rate post-surgery remains high and a significant proportion of CD patients require more than one operation. This can result in specific nutritional deficiencies or short gut syndrome if extensive resection is carried out. In view of these issues, there has been renewed interest in endoscopic therapy for CD-related strictures. Previous studies have shown that endoscopic management is effective and has the best outcomes in strictures which are short (4 cm or less), non-angulated and uncomplicated (i.e., no extensive ulcerations, fistulation, abscess, or perforation).6 Current endoscopic therapies include endoscopic balloon dilation (EBD), endoscopic stricturotomy (ES), and the placement of removable or biodegradable self-expanding metallic stent (SEMS). In a recent issue, Partha Pal et al. prospectively looked at re-intervention rates and symptom-free survival at 1 year after endoscopic therapy (ET) versus surgical management of CD-related strictures.7 This retrospective study used propensity score matched analysis found that ET prevented surgery in the majority of patients (> 90%) over the follow-up duration although not surprisingly, re-interventions were more common in ET group. Other outcomes such as symptom-free survival, need for escalation of therapy, and re-operation were comparable to the surgical arm. Although the re-intervention rate was higher, repeated procedures were safely carried out using EBD or ES. In this study, EBD was used as the primary ET. This finding is consistent with a previous meta-analysis looking specifically at EBD.6 However, the real question is whether the newer therapies such as ES or stent placement combined with advanced therapy to control inflammation may be able to prevent surgery in the majority of patients altogether. A large study comparing EBD versus ES found that the need for surgery was only 9.5% in the ES group versus 89.5% in the EBD group. In terms of complications, the perforation rate was 1.1% in the EBD group and none in the ES group, but in contrast, there was a higher bleeding rate in the ES group.8 A small study comparing EST and ileo-colonic resection in patients with primary CD-related ileum strictures found that the subsequent surgical rates were similar between the two groups with a numerically lower rate of complications in the EST group.9 Although at present this procedure is limited to specialized centers, ES shows promise in providing results very similar to surgery. Endoscopic management for IBD has been relatively underdeveloped compared to other conditions but hopefully, this will change over time and may encompass treatment of other complications such as fistulas.10 Nevertheless, the management of CD-related strictures is complex, and many unanswered questions remain. It is essential that each decision is carefully made on an individualized basis and using a multi-disciplinary approach. The authors confirm that the data supporting the findings of this study are available within the article.