Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns in patients with inflammatory bowel disease (IBD), not only due to consequences of coronavirus disease 2019 itself but also as a possible cause of IBD relapse. The main objective of this study was to assess the role of SARS-CoV-2 in IBD clinical recurrence in a cohort of patients undergoing biological therapy. Second, we evaluated the difference in C-reactive protein (CRP) levels between the start and end of the follow-up period (ΔCRP) and the rate of biological therapy discontinuation. Patients with IBD positive for SARS-CoV-2 infection were compared with non-infected patients. IBD recurrence was defined as the need for intensification of current therapy. We enrolled 95 IBD patients with SARS-CoV-2 infection and 190 non-infected patients. During follow-up, 11 of 95 (11.6%) SARS-CoV-2-infected patients experienced disease recurrence compared to 21 of 190 (11.3%) in the control group (p = 0.894). Forty-six (48.4%) SARS-CoV-2-infected patients discontinued biological therapy versus seven (3.7%) in the control group (p < 0.01). In the multivariate analysis, biological agent discontinuation (p = 0.033) and ΔCRP (p = 0.017), but not SARS-CoV-2 infection (p = 0.298), were associated with IBD recurrence. SARS-CoV-2 infection was not associated with increased IBD recurrence rates in this cohort of patients treated with biological agents.

Interleukin-23 (IL-23) is a key cytokine involved in the pathogenesis of various immuno-mediated inflammatory diseases. In recent years, several drugs selectively targeting IL-23 have been developed and three of them (mirikizumab, risankizumab and guselkumab) were successfully investigated in clinical trials for ulcerative colitis (UC). All of them showed a good profile for efficacy, alleviating symptoms, and inducing endoscopic and histologic improvement, with very low incidence of adverse events. Bowel urgency also emerged as a crucial outcome from patients’ perspective in the mirikizumab trials. The correct positioning of IL-23 inhibitors in the therapeutic algorithm for UC represents a new challenge for physicians, especially because it is not guided by biomarkers or predictors of effectiveness. Moreover, no comparative clinical data exist among the available IL-23 inhibitors, although molecular differences might potentially impact their effectiveness. A role for IL-23-inhibitors may also lie in combination with drugs with different mechanisms of action for complex, multi-refractory patients. This review, focusing on UC, summarizes all the clinical data available on IL-23 inhibitors and provides a perspective on the best clinical scenarios to maximize their effectiveness.

Ulcerative colitis (UC) is a chronic progressive inflammatory bowel disease, with evolutive potential for extension to the entire colon, development of complications and need for colectomy. Therapeutic goals in UC have moved from symptom control to more stringent outcomes such as endoscopic and histologic remission, which have been observed to correlate with improved long-term outcomes. Disease clearance, a composite endpoint simultaneously including clinical remission, endoscopic and histologic healing, has been recently proposed as the ultimate target. A treat-to-target approach, as endorsed by the STRIDE II consensus, with a tight monitoring and treatment escalation when predefined endpoints are not reached, is proposed as a strategy to achieve complete disease control. However, unlike Crohn’s disease (CD), the evidence supporting this approach for the management of UC is limited and its implementation in routine clinical practice is not widely diffused. Recent real-life data show that almost half of UC patients are not adequately controlled with current therapies according to STRIDE II criteria, due to steroid overuse, persistent signs of inflammation, active extra-intestinal manifestations and impaired quality of life. This perspective paper explores current evidence and future directions on treat-to-target strategies in UC for clinical research and practice.

Background/Objectives: Crohn’s disease (CD) is one of the most frequent causes of short bowel syndrome (SBS), a severe clinical condition with huge morbidity and social costs. SBS occurs when, following intestinal resections, the remaining small bowel in continuity is less than 200 cm in length. Intestinal failure (IF) can complicate SBS when intravenous nutritional or electrolyte supplementation is required to maintain dietary needs. The primary aim of this study was to identify clinical predictive factors of SBS in a cohort of outpatients with CD. Methods: We conducted a prospective, single-center, cohort study enrolling consecutive CD outpatients at a tertiary-level inflammatory bowel disease center. Detailed demographic and clinical features were collected. Significant factors associated with the onset of SBS in the univariate analysis were input into a multivariate logistic regression model to identify independent predictors of SBS. Results: In total, 232 CD patients (52.6% male, median age 49 years [IQR 37–60]) were included: 24.6% of them were smokers; extraintestinal manifestations (EIMs) were present in 21.6% of patients; and 67.7% of patients had at least one intestinal resection (27% of them with more than one surgical intervention). At enrollment, 96.1% of patients were on advanced therapies, and considering the course of the disease, 24.6% of patients were exposed to ≥3 different advanced therapies. A total of 18 patients had SBS and 9 had IF. In univariate analysis, the following variables were statistically associated with the risk of developing SBS: disease duration (p < 0.001), upper gastrointestinal disease localization (L4) (p < 0.001), penetrating behavior (p = 0.023), perianal disease (p = 0.036), length of first intestinal resection (p < 0.001), shorter time elapsing from CD diagnosis to start the first advanced therapy (p < 0.001), and treatment with advanced therapy after first intestinal resection (p < 0.001). In multivariate analysis, disease duration (OR 1.083, 95% C.I. 1.025–1.145, p = 0.005) and L4 (OR 20.079, 95% C.I. 2.473–163.06, p = 0.005) were independently associated with the development of SBS. Conversely, the number of different advanced therapies before the onset of SBS was independently associated with a reduced risk of developing SBS (OR 0.247, 95% C.I. 0.107–0.58, p = 0.001). Conclusions: Our data identifies several clinical features that could possibly predict the development of SBS in CD. Further studies with a larger sample size are needed to confirm our findings.

Vedolizumab has demonstrated efficacy in randomized trials on postoperative Crohn's disease; however, real-world data on both prophylaxis and treatment of recurrence are limited. In this retrospective multicenter study, patients with Crohn's disease treated with vedolizumab after ileocolonic resection (2018-2024) were included. Patients were stratified into a prophylaxis cohort and a recurrence-treatment cohort. Severe endoscopic recurrence (Rutgeerts ≥i3) at 6-12 months was the primary endpoint in the prophylaxis cohort. Endoscopic response (≥1-point Rutgeerts reduction) at a follow-up colonoscopy within 2 years, was evaluated in the treatment cohort. Treatment failure was defined as discontinuation of vedolizumab due to any reason. Treatment persistence was analyzed using Kaplan-Meier and multivariable Cox regression models. A total of 108 patients were included; 50 received vedolizumab as postoperative prophylaxis. Severe endoscopic recurrence occurred in 22% of prophylaxis patients. Prior intestinal resection (OR 5.24, 95% CI 1.03-26.61; p = 0.046) and younger age at surgery (OR 0.93, 95% CI 0.87-0.99; p = 0.042) were independently associated with severe recurrence. In the recurrence cohort (n = 58), endoscopic response was 44.8%. Overall VDZ failure occurred in 31.5%. Prophylactic use was independently associated with reduced failure (HR 0.17, 95% CI 0.05-0.53; p = 0.002). Vedolizumab showed sustained effectiveness for postoperative prophylaxis and more modest effectiveness in established recurrence.

Background: Surgical management of hemorrhoidal disease (HD) in patients with IBD remains controversial because of concerns about impaired outcomes. This study aimed to evaluate the safety and IBD-related outcomes of surgical treatments for HD in patients with IBD and to explore factors potentially associated with postoperative complications and IBD flare. Methods: HEAD-IBD is a retrospective cohort study promoted by the Italian Group for the study of IBD (IG-IBD). Adults with established ulcerative colitis (UC) or Crohn’s disease (CD) who underwent surgery for HD between 2004 and 2024 and had at least 12 months of follow-up were included. Surgical techniques, 1-, 6-, and 12-month complications, IBD flares (6 months), new onset perianal disease, and continence outcomes were analyzed. Results: A total of 38 patients were included (21 UC, 17 CD), 55% male. Clinically active disease at the last gastroenterology visit prior to surgery was present in 24% of UC and 41% of patients with CD. Open excisional hemorrhoidectomy was the most frequently performed procedure in both groups (66% UC, 73% CD), while non-excisional techniques were used in approximately one-third of cases. No 30-day or 6-month surgical complications occurred in patients with CD. Postoperative surgical complications were observed exclusively in patients with UC (5/21, 24%) and were mostly mild. Within 6 months after surgery, IBD flares occurred in 6 patients (16%), proportionally comparable between CD and UC. During overall follow-up, new-onset perianal disease developed in 5 patients (13%), predominantly in CD (4/5 cases), while new-onset incontinence was observed in 2 (5%) patients, both managed conservatively. Conclusions: In this largest European multicenter cohort, surgical treatment of HD in IBD was associated with low morbidity and preservation of anorectal function. These findings support a more individualized approach and underscore the need for prospective studies.