INTRODUCTION: To update the global burden of inflammatory bowel disease (IBD) using data from the Global Burden of Disease 2021. METHODS: Data from Global Burden of Disease 2021 were analyzed to assess the IBD burden. RESULTS: In 2021, there were 375,140 new cases and 3.83 million total cases of IBD. Elderly onset IBD accounted for 11% of incidences. 167 countries increased IBD incidence rate, with rates rising in female patients (APC: +0.06%) and the elderly (APC: +0.14%) but stable in male patients and the overall population. DISCUSSION: Although the global burden of IBD has decreased overall, it has increased in female patients and the elderly.

Fistulizing Crohn’s disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30–50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.

Biologicals and small molecules have revolutionized the medical management of inflammatory bowel diseases (IBD), yet they are only effective in a proportion of patients, and their impact on changing the natural history of the disease is still debatable. Recently, the concept of combining targeted biologics and small-molecule therapies has been introduced to the treatment of IBD. Dual-targeted therapy (sequential and combined), which is the combination of two targeted therapies, might be a reasonable choice for patients to break through the therapeutic ceiling. A recent randomized clinical trial (VEGA) provided the first controlled evidence that the short-term combination of two biological agents may lead to superior disease control than either of the agents alone in patients with ulcerative colitis (UC) without jeopardizing safety. Multiple studies are underway in both Crohn’s disease and UC. Additionally, real-world evidence is accumulating in IBD patients receiving combination therapies with concomitant IBD and extraintestinal manifestations or in patients with medically refractory IBD. Of note, the majority of these patients were exposed to multiple biological agents earlier and lost response to at least one of the agents in the combination. This review summarizes current knowledge regarding this attractive novel therapeutic option in IBD. Clearly, more controlled data are needed to evaluate optimal timing, efficacy, and mitigation of safety concerns.

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.

Background and Aims. Tissue-invasive gastrointestinal cytomegalovirus (TI-GI CMV) disease is common in immunocompromised patients, but the increasing prevalence in immunocompetent patients has been reported. This study compared the clinical manifestations, endoscopic features, treatment outcomes, and predictors for inhospital mortality of TI-GI CMV between immunocompromised and immunocompetent patients. Methods. Patients with HIV infection, malignancy, or receiving immunosuppressive agents (chemotherapy, high dose, or long-term corticosteroids) were defined as the immunocompromised group. Demographic and inhospital mortality data were obtained and retrospectively analyzed. Results. A total of 213 patients (89 immunocompetent) with histologically confirmed TI-GI CMV were enrolled. Immunocompetent patients were older (70 vs. 52 years; ), had more GI bleeding as a presenting symptom (47.2% vs. 29.0%; ), and shorter symptom onset (2 vs. 14 days, ). Concomitant extra-GI involvement was only seen in the immunocompromised group (6.5% vs. 0%; ). Diffuse GI tract (14.5% vs. 4.5%; ) and esophageal involvement (14.5% vs. 5.6%; ) were more frequent in the immunocompromised, while small bowel involvement was more frequent in the immunocompetent group (19.1% vs. 8.1%; ). An overall inhospital mortality was 27.7%. There was no significant difference in inhospital survival probability between the two groups (Peto-Peto test, ). ICU admission (hazard ratio [HR] 7.21; 95% CI 2.55-20.36), sepsis or shock (HR 1.98; 95% CI 1.08-3.66), malnutrition (HR 2.62; 95% CI 1.05-7.01), and receiving chemotherapy (HR 5.2; 95% CI 1.89-14.29) were independent factors for inhospital mortality. Antiviral treatment for more than 14 days was the only protective factor to improve survival (Peto-Peto test, ). Conclusions. Immunocompetent and immunocompromised patients with TI-GI CMV disease had distinct clinical and endoscopic characteristics. There was no significant difference in the inhospital mortality between the two groups. The factors for mortality were ICU admission, sepsis/shock, malnutrition, and receiving chemotherapy. Early diagnosis and initiation of antiviral treatment might improve the survival probability.

Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9–12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4–10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7–3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6–2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.