Management of proctitis in ulcerative colitis and the place of biological therapies.

INTRODUCTION: Approximately 20-30% of the patients with ulcerative colitis (UC) may present with isolated proctitis. Ulcerative proctitis (UP) is a challenging condition to manage due to its significant burden in terms of disabling symptoms. AREAS COVERED: PubMed was searched up to March 2024 to identify relevant studies on UP. A comprehensive summary and critical appraisal of the available data on UP are provided, highlighting emerging treatments and areas for future research. EXPERT OPINION: Patients with UP are often undertreated, and the disease burden is often underestimated in clinical practice. Treat-to-target management algorithms can be applied to UP, aiming for clinical remission in the short term, and endoscopic remission and maintenance of remission in the long term. During their disease, approximately one-third of UP patients require advanced therapies. Escalation to biologic therapy is required for refractory or steroid dependent UP. For optimal patient care and management of UP, it is necessary to include these patients in future randomized clinical trials.

Management of Post-Operative Crohn's Disease: Knowns and Unknowns.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing-remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20-30% of subjects may not experience endoscopic POR and that 40-50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient's risk of recurrence) or starting therapy after confirming endoscopic POR 6-12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options.

Adalimumab Biosimilar in Pediatric Inflammatory Bowel Disease: A Retrospective Study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

BACKGROUND: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. METHODS: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. RESULTS: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). CONCLUSIONS: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective.

Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.

Small Bowel Imaging in Celiac Disease: Is there a role for Small Bowel Ultrasound?

PURPOSE OF REVIEW: The incidence of celiac disease (CD) has increased over the last decades in part due to better disease awareness. Small bowel ultrasound (sb US) enables dynamic assessment of the bowel; although this topic has been addressed, the use of sb US in the diagnosis and in the follow-up of CD patients is limited to a few specialized tertiary referral centers. Herein, we aimed at summarizing the available literature on this topic to better define the potential clinical implications of sb US in CD, also through a comparison with other available diagnostic techniques. RECENT FINDINGS: According to available data, sb US can be of help in confirming or excluding CD in patients with clinical suspicion; specifically, the finding of increased gall bladder volume, free abdominal fluid and enlargement of mesenteric lymph nodes reliably and accurately predicts the diagnosis of CD, whereas the absence of bowel dilatation and increased peristalsis may exclude the diagnosis. However, the place of intestinal US in the diagnostic algorithm of CD is likely to vary depending on the probability of the disease in a given population. There are only a few studies on the role of sb US in complicated CD, even if recent reports suggest a possible clinical role. There is a lack of data on follow-up of CD patients, particularly with the aim of detecting a poor diet adherence. According to current data sb US parameters have been shown to be of value in confirming and excluding the diagnosis of CD. Prospective studies with large sample size are warranted to determine whether to include sb US in the available guidelines for CD diagnosis and monitoring.

Endoscopy Ultrasound-Guided Biliary Drainage Using Lumen Apposing Metal Stent in Malignant Biliary Obstruction.

This narrative review provides an overview of the application of endoscopic ultrasound-guided biliary drainage (EUS-BD), including EUS-guided gallbladder drainage (EUS-GBD), for the treatment of malignant biliary obstruction. EUS-BD has demonstrated excellent technical and clinical success rates, with lower rates of adverse events when compared with percutaneous trans-hepatic biliary drainage (PTBD). EUS-BD is currently the preferred alternative technique for biliary drainage (BD) in patients with distal malignant biliary obstruction (DMBO) after failed endoscopic retrograde cholangiopancreatography (ERCP). Particularly, this review will focus on EUS-BD performed with the use of lumen apposing metal stent (LAMS). The introduction of these innovative devices, followed by the advent of electrocautery-enhanced LAMS (EC-LAMS), gave the procedure a great technical implementation and a widespread application.

Mental Illnesses in Inflammatory Bowel Diseases: mens sana in corpore sano.

Background and aims: Inflammatory bowel diseases (IBD) are chronic disorders associated with a reduced quality of life, and patients often also suffer from psychiatric comorbidities. Overall, both mood and cognitive disorders are prevalent in chronic organic diseases, especially in the case of a strong immune component, such as rheumatoid arthritis, multiple sclerosis, and cancer. Divergent data regarding the true incidence and prevalence of mental disorders in patients with IBD are available. We aimed to review the current evidence on the topic and the burden of mental illness in IBD patients, the role of the brain-gut axis in their co-existence, and its implication in an integrated clinical management. Methods: PubMed was searched to identify relevant studies investigating the gut-brain interactions and the incidence and prevalence of psychiatric disorders, especially of depression, anxiety, and cognitive dysfunction in the IBD population. Results: Among IBD patients, there is a high prevalence of psychiatric comorbidities, especially of anxiety and depression. Approximately 20-30% of IBD patients are affected by mood disorders and/or present with anxiety symptoms. Furthermore, it has been observed that the prevalence of mental illnesses increases in patients with active intestinal disease. Psychiatric comorbidities continue to be under-diagnosed in IBD patients and remain an unresolved issue in the management of these patients. Conclusions: Psychiatric illnesses co-occurring in IBD patients deserve acknowledgment from IBD specialists. These comorbidities highly impact the management of IBD patients and should be studied as an adjunctive therapeutic target.

Artificial intelligence and inflammatory bowel disease: Where are we going?

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, are chronic and relapsing conditions that pose a growing burden on healthcare systems worldwide. Because of their complex and partly unknown etiology and pathogenesis, the management of ulcerative colitis and Crohn's disease can prove challenging not only from a clinical point of view but also for resource optimization. Artificial intelligence, an umbrella term that encompasses any cognitive function developed by machines for learning or problem solving, and its subsets machine learning and deep learning are becoming ever more essential tools with a plethora of applications in most medical specialties. In this regard gastroenterology is no exception, and due to the importance of endoscopy and imaging numerous clinical studies have been gradually highlighting the relevant role that artificial intelligence has in inflammatory bowel diseases as well. The aim of this review was to summarize the most recent evidence on the use of artificial intelligence in inflammatory bowel diseases in various contexts such as diagnosis, follow-up, treatment, prognosis, cancer surveillance, data collection, and analysis. Moreover, insights into the potential further developments in this field and their effects on future clinical practice were discussed.

Advancements in Endoscopic Resection for Colitis-Associated Colorectal Neoplasia in Inflammatory Bowel Disease: Turning Visible into Resectable.

Patients suffering from inflammatory bowel disease (IBD) face a two to three-fold higher risk of developing colorectal cancer (CRC) compared to the general population. In recent years, significant progress has been made in comprehending the natural history of IBD-associated CRC (IBD-CRC) and refining its treatment strategies. The decreased incidence of IBD-CRC can be attributed to improved therapeutic management of inflammation, advancements in endoscopy, and early detection of precancerous lesions via surveillance programs. Advanced imaging technologies have made previously undetectable dysplasia visible in most cases, allowing for a much more precise and detailed examination of the mucosa. Additionally, new tools have facilitated the endoscopic resection (ER) of visible lesions in IBD. Particularly, the key to effectively manage colitis-associated colorectal neoplasia (CAN) is to first identify it and subsequently guarantee a complete ER in order to avoid surgery and opt for continuing surveillance. Advanced ER techniques for CAN include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and hybrid ESD-EMR (h-ESD). This narrative review aims to consolidate the current literature on IBD-CRC, providing an overview of advanced techniques for ER of CAN in IBD, with a particular emphasis on the impact of ESD on the long-term outcomes of IBD patients.

Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease.

OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

SPOSAB ABP 501: A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501.

BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Perception of the Role of Food and Dietary Modifications in Patients with Inflammatory Bowel Disease: Impact on Lifestyle.

BACKGROUND: Diet has a relevant role in triggering symptoms in inflammatory bowel disease (IBD) from the patients' perspective, but there is gap the between patients' and doctors' perceptions. Few studies have addressed this topic. The aim of this study was to evaluate food habits and nutrition knowledge in a homogeneous cohort of patients with IBD from southern Italy. METHODS: 167 consecutive patients with IBD were recruited. The survey was based on the administration of a semi-structured questionnaire assessing demographics, disease features, dietary behavior, and food intolerance. RESULTS: The majority of patients did not consider food a cause of their disease. However more than 80% changed their diet after the diagnosis and most report an improvement in symptoms. Spiced and seasoned foods, dairy products, vegetables, and fruit were often avoided. A dairy-free diet was adopted by 33.7%. Food choices were based on self-experience and not on medical counselling. Dietary modifications deeply impact on lifestyle. CONCLUSIONS: Most of the patients with IBD set diet and lifestyle on self-experience and give up many foods. This has an impact on psychosocial functioning and can lead to nutritional deficiencies. High quality studies are warranted to assess evidence-based dietary strategies and develop patient-targeted dietary recommendations.

Systemic therapies for hepatocellular carcinoma: the present and the future.

Hepatocellular carcinoma is diagnosed in more than half of all cases at unresectable stage when no potentially curative treatments are feasible. Since 2008, sorafenib had represented the only effective first line systemic therapy over the last decade until the approval of lenvatinib, who showed to be non-inferior to sorafenib. Recently, for the first time, a combination of immunotherapy and antiangiogenic drug, atezolizumab plus bevacizumab, was associated with a significantly longer overall survival and progression free survival compared to sorafenib, becoming the new best performing first-line approach for unresectable HCC. After several randomized controlled trials (RCTs) that have attempted to find an effective second-line therapy, regorafenib, cabozantinib, ramucirumab, nivolumab and pembrolizumab represent approved treatments for patients who failed first-line treatment. However, inclusion criteria of second-line RCTs are quite heterogeneous and no direct comparisons exist among these agents. Exciting opportunities have been found either in the combination or in the sequencing of these agents, but the optimal therapeutic strategy for these patients remains elusive. Moreover, the coexistence of cirrhosis and the competing risk of liver decompensation increase the complexity of the assessment of the net health benefit of the available therapeutic approaches. The aim of this review is to summarize the evidence on systemic treatments for unresectable HCC and to explore the future perspectives on this topic.

Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

BACKGROUND& AIMS: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. METHODS: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS were evaluated by the coefficient of determination R2 . RESULTS: We identified 13 studies comparing TACE vs systemic therapy or vs TACE plus systemic therapy and including 1932 TACE-treated patients. Pooled median OS was 11.2 months (95% confidence interval [95%CI] 7.9-17.8), and pooled median TTP was 5.4 months (95%CI 3.8-8.0). Heterogeneity among studies was highly significant for both outcomes. The correlation between HR TTP and HR OS was moderate (R2  = 0.65. 95%CI 0.08-0.81). R2 value was 0.04 (95%CI 0.00-0.35) between median TTP and median OS. CONCLUSION: In studies of TACE for u-HCC, the surrogate relationship of radiology-based endpoints with OS is moderate. Multiple endpoints including hepatic decompensation, macrovascular invasion and extrahepatic spread are needed for future trials comparing systemic therapies or combination of TACE with systemic therapies vs TACE alone.

A propensity score weighted comparison of vedolizumab and adalimumab in Crohn's disease.

BACKGROUND AND AIM: There are no head-to-head randomized controlled trials between biologics in Crohn's disease (CD). We aimed to perform a multicenter, real-life comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD. METHODS: Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. The effectiveness was evaluated at 12, 52 weeks, and as failure-free survival at the end of follow up. Propensity score analysis was performed using the inverse probability of treatment weighting method. RESULTS: Five hundred eighty-five treatments (VDZ: n = 277; ADA: n = 308) were included (median follow-up: 56.0 weeks). After 12 weeks, a clinical response was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.38-1.10, P = 0.107), while at 52 weeks, a clinical response was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (OR 0.77, 95% CI 0.45-1.31, P = 0.336). Cox survival analysis weighted for propensity score showed no significant difference in the probability of failure-free survival between the two drugs (hazard ratio = 1.20, 95% CI 0.83-1.74, P = 0.340). Post-treatment endoscopic response and mucosal healing rates were similar between the two groups (endoscopic response: 35.3% for VDZ and 25.5% for ADA, P = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, P = 0.85). CONCLUSIONS: In the first study comparing VDZ and ADA in CD via propensity score analysis, the drugs showed comparable effectiveness and a similar safety profile.

Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma.

BACKGROUND: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. METHODS: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan-Meier curves. Summary median PFS and OS data were obtained from random-effect model. The surrogate relationships of median PFS, first quartile (Q1), third quartile (Q3), and restricted mean survival time (RMST) for OS were evaluated by the coefficient of determination R2. Heterogeneity was explored by meta-regression. RESULTS: We identified 49 trials, 11 assessing immune-checkpoint inhibitors (ICIs) and 38 multikinase inhibitors (MKIs). Overall, the correlation between median PFS and median OS was weak (R2 = 0.20. 95% Confidence Intervals [CI]-0.02;0.42). Surrogacy robustness varied between treatment classes and PFS endpoints. In ICI trials only, the correlations between Q1-PFS and Q1-OS and between 12-month PFS-RMST and 12-month OS-RMST were high (R2 = 0.89, 95%CI 0.78-0.98, and 0.80, 95% CI 0.63-0.96, respectively). Interaction p-values obtained by meta-regression confirmed the robustness of results. CONCLUSIONS: In trials of systemic therapies for advanced HCC, the surrogate relationship of PFS with OS is highly variable depending on treatment class (ICI or MKI) and evaluation time-point. In ICI trials, Q1-PFS and 12-month PFS-RMST are robust surrogate endpoints for OS.