Introduction: Sequencing therapy for Crohn’s disease (CD) is currently being intensively discussed due to the development of novel drugs and lack of standardized criteria for drug positioning in first- and further-line treatment. The aim of this study was to compare the efficacy of a second-line advanced therapy in Romanian patients with CD who have failed an anti-TNF agent. Methods: We performed a multicenter retrospective study that included adult patients with CD who had secondary loss of response after an initial response with an anti-TNF drug. The main outcome was clinical remission at 12 weeks of second-line treatment (CDAI < 150). The secondary outcomes included clinical response (decrease in CDAI ≥ 70 points), persistence of therapy at 1 year and rates of adverse events. Results: From 2008 to 2024, 216 patients were either switched to another anti-TNF or swapped to another therapeutic class, due to the failure of a first anti-TNF drug. Secondary lines of treatment included infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST). The highest rate of clinical remission (81%) was obtained with the sequence ADA-IFX in 26/32 (81%) patients and ADA-UST in 62/82 (76%) patients, followed by IFX-UST in 22/33 (67%) and IFX-ADA 34/51 (67%). Persistence in therapy at 1 year was better for the sequence ADA-UST (73%) and IFX-UST (67%) and ADA-IFX (63%) compared to IFX-ADA (59%) and IFX-VDZ (44%) (p < 0.001). Conclusions: There were significant baseline differences between the treatment groups, so this study represents an unadjusted comparison between the results obtained with different biologics in second-line treatment for Crohn’s disease. In patients with CD who have failed a first anti-TNF, the highest rate of clinical remission at 12 weeks was obtained with second-line IFX and UST whilst vedolizumab showed lower efficacy. UST demonstrated the most favorable long-term treatment persistence at 1 year.

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC), chronic immune-mediated conditions of the gastrointestinal tract characterized by alternating periods of disease activity and remission with a complex multifactorial pathogenesis. Persistent intestinal inflammation in IBD is a key driver of disease progression and is strongly associated with the development of complications such as dysplasia, colorectal cancer (CRC), intestinal strictures, and fistulas. It may also result in changes in anorectal function, identifiable and classifiable using high-resolution anorectal manometry. Histologic and endoscopic assessments are essential for the evaluation of intestinal inflammation. Cumulative inflammatory burden (CIB) is an important concept that quantifies inflammatory exposure in IBD over time by integrating the severity and duration of histologic inflammation across the disease course, highlighting the importance of long-term inflammatory activity in the development of CRC. Histologic healing may be an important therapeutic target in IBD to reduce the risk of long-term complications. In parallel, emerging precision medicine approaches aim to improve risk stratification and enable early, individualized interventions to reduce disease-related outcomes. Endoscopy also plays a fundamental role in monitoring high-risk patients and guiding treatment decisions. This review aims to characterize the main intestinal complications extending beyond the mucosa that are associated with cumulative chronic inflammation in patients with IBD, including dysplasia, CRC, strictures, fistulas, and anorectal dysfunction in an era increasingly focused on achieving complete mucosal healing. Particular attention is drawn to the significant role of persistent histologic and endoscopic inflammation in disease progression and development of complications, highlighting the specific features and associated risk factors of these disease-related outcomes. Throughout, this review emphasizes the fundamental role of endoscopy in the timely detection, monitoring, and therapeutic management of IBD-related complications, thereby reinforcing its role in comprehensive patient care.

Background: Small-bowel bleeding accounts for a minority of gastrointestinal hemorrhage and may pose a diagnostic challenge after negative bidirectional endoscopy. Malignant melanoma involving the small intestine is usually metastatic, whereas a true primary small-bowel melanoma is exceptionally rare and remains controversial. Case Report: We report the case of a 76-year-old female patient who presented with severe symptomatic iron-deficiency anemia and recurrent overt gastrointestinal bleeding. Esophagogastroduodenoscopy and colonoscopy did not identify a bleeding source. Cross-sectional imaging demonstrated a large necrotic mass in the inter-gastro-jejunal region, initially interpreted as a possible gastrointestinal stromal tumor (GIST). Endoscopic ultrasound showed a heterogeneous lesion exceeding 100 mm and enabled fine-needle biopsy. Histopathology demonstrated a malignant epithelioid amelanotic melanoma with diffuse SOX10, S100, and Melan-A expression and a high proliferative index. Concomitant CD117 positivity represented a potential diagnostic pitfall given the initial suspicion of a GIST. Enteroscopy subsequently documented a large ulcerated jejunal lesion with friable mucosa and stigmata of recent bleeding, demonstrating luminal involvement and ascertaining it as the likely source of blood loss. Dermatologic and ophthalmologic examinations revealed no alternative primary melanoma. Conclusions: This case illustrates the complementary roles of cross-sectional imaging, EUS-guided tissue acquisition, and enteroscopy in a tumor that mimicked a GIST, while emphasizing that absence of an identifiable extraintestinal primary does not by itself prove a primary intestinal origin.

Introduction: Sequencing therapy in CD is currently intensively discussed due to the development of novel drugs and lack of standardized criteria for drug positioning in first and further treatment lines. The aim of this study was to compare the efficacy of a second line advanced therapy in Romanian patients with CD who have failed an anti-TNF agent. Methods: We performed a multicenter retrospective study that included adult patients with CD who had secondary loss of response after an initial response with an an-ti-TNF drug. The main outcome was clinical remission at 12 weeks of second-line treatment (CDAI < 150). Secondary outcomes included clinical response (decrease of CDAI ≥ 25%), persistence of therapy at 1 year and rates of adverse events. Results: From 2008 to 2024, 216 patients were either switched to another anti-TNF or swapped to another therapeutic class due to failure of a first anti-TNF drug. Secondary lines of treatment in-cluded infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST). The highest rate of clinical remission (81%) was obtained with the sequence ADA-IFX in 26/32(81%) patients and ADA-UST in 62/82(76%) patients, followed by IFX-UST in 22/33(67%) and IFX-ADA 34/51(67%). Persistence on therapy at 1 year was better for the sequence ADA-UST(73%) and IFX-UST(67%) and ADA-IFX(63%) compared to IFX-ADA(59%) and IFX-VDZ(44%)(p< 0.001). Conclusions: In patients with CD who have failed a first anti-TNF, the highest rate of clinical re-mission at 12 weeks was obtained with second line IFX and UST whilst vedolizumab showed lower efficacy. UST demonstrated the most favorable long-term treatment persistence at 1 year.

Background and Objectives: Biologic agents have emerged as the most important therapeutic weapon in the treatment of Crohn’s disease (CD). The aim of this study is to describe the population of patients who received different molecules as first-line therapy and their persistence on first-line therapy. Materials and Methods: 622 patients from six gastroenterology departments from Bucharest, Iasi and Cluj treated between 2006 and 2024 were included in the study. A total of 87 (14%) were excluded because they received only mesalazine. A total of 535 were included in the final analysis. The main outcomes were clinical response and remission at 12 weeks of treatment and serious adverse events. Results: Three groups of patients were identified based on the first-line treatment: 45% of patients received adalimumab, 40% were treated with infliximab, and in 12.6% ustekinumab was given. Regarding the clinical and demographic characteristics, there are significant differences among the three patient groups in terms of age, disease extent, disease phenotype, proportion of individuals with perianal fistulas, clinical severity and the proportion of patients who underwent surgery. Median therapy duration was 48 months (6 ÷ 330). The three biologics studied (adalimumab, infliximab and ustekinumab) had a similar rate of clinical remission of 80%, the non-response rate also being similar (6.5%), but persistence on therapy at 2 years was better for adalimumab (66%) and infliximab (60%) compared to ustekinumab (45%) (p = 0.06). Serious adverse events leading to therapy discontinuation were more frequent in those treated with infliximab (10%) compared to adalimumab (3%) and ustekinumab (6%) (p = NS). Conclusions: There were significant baseline differences between the treatment groups, so this study represents an unadjusted comparison between the results obtained with different biologics in first-line treatment for Crohn’s disease. All three biological agents used in real life for Crohn’s disease therapy show similar efficacy, with an early clinical remission rate of approximately 80% and a non-response rate of 6.5%.