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Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Abstract Dietary therapy is increasingly recognized for the management of Crohn’s disease (CD) over recent years, including the use of exclusive enteral nutrition (EEN) as first-line therapy for pediatric CD according to current guidelines. The Crohn’s disease exclusion diet (CDED) is a whole-food diet designed to reduce exposure to dietary components that are potentially pro-inflammatory, mediated by negative effects on the gut microbiota, immune response, and the intestinal barrier. The CDED has emerged as a valid alternative to EEN with cumulative evidence, including randomized controlled trials, supporting use for induction of remission and possibly maintenance in children and adults. We gathered a group of multidisciplinary experts, including pediatric and adult gastroenterologists, inflammatory bowel diseases (IBD) expert dietitians, and a psychologist to discuss the evidence, identify gaps, and provide insights into improving the use of CDED based on a comprehensive review of CDED literature and professional experience. This article reviews the management of CDED in both children and adults, long-term aspects of CDED, indications and contraindications, selecting the best candidates, identifying challenges with CDED, globalization, the role of the multidisciplinary team, especially of dietitian, and future directions. We concluded that CDED is an established dietary therapy that could serve as an alternative to EEN in many pediatric and adult cases, especially with mild to moderate disease. In severe disease, complicated phenotypes, or with extraintestinal involvement, CDED should be considered on a case-by-case basis, according to physician and dietitians’ discretion. More studies are warranted to assess the efficacy of CDED in different scenarios. Lay Summary The Crohn’s disease exclusion diet (CDED) has emerged as an alternative to exclusive enteral nutrition for the treatment of pediatric Crohn’s disease. In this review, we summarize data on efficacy and challenges and identify research priorities, clinical gaps, and opportunities.

Introduction Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based cohort. Methods 48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979–2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-α (TNF-α) blockers, and of first minor or major surgery according to period of diagnosis, was estimated. Medication use and risk of surgery was examined by Cox regression. Results 5-year cumulative probability of first major surgery decreased from 44.7% in cohort (1979–1986) to 19.6% in cohort (2003–2011) (p < 0.001) for CD, and from 11.7% in cohort (1979–1986) to 7.5% in cohort (2003–2011) (p < 0.001) for UC. Minor surgery risk decreased significantly in CD. From cohort (1995–2002) to cohort (2003–2011), a significant increase in use of thiopurines and TNF-α blockers was observed, paralleled by a significant decrease in use of 5-ASA and corticosteroids. Comparing use of azathioprine (or oral corticosteroids) to never-use, no convincing surgery-sparing effect was found. Comparing use in 3+ months of a given drug with use <3 months, only 3+ months use of oral corticosteroids reduced the risk of surgery in patients with disease duration of >1 year. Conclusions Parallel to an increasing use of thiopurines and TNF-α blockers in IBD over time, a persistent significant decrease in surgery rates was observed along with a significant decrease in use of 5-ASA and corticosteroids. However, no convincing surgery-sparing effect of newer medications was found.

ObjectiveTo review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD).MethodsData were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported.ResultsOf 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data.ConclusionThis extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn’s Disease. Methods: 18 patients with mild/moderate CD (PCDAI 15–45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. Results: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. Conclusions: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.

Intestinal penetrating complications of Crohn's disease (CD) are challenging issues, but it is difficult to decide between medical treatment and surgery. This study aimed to evaluate the outcomes of medical and surgical therapy in patients with non-perianal fistulizing CD. Our study aimed to evaluate and compare the effectiveness of surgery and medical treatment in CD patients with non-perianal fistulas. This retrospective study included all CD patients with non-perianal fistulas. We evaluated the outcomes of medical and surgical therapy. Fistula closure was identified with radiological examinations or ultrasound. Cox regression analysis was subsequently performed. Sixty patients (37 male) were included. 43.3% of the patients received biological agents as the first therapy, whereas 55% required surgery as the initial therapy, and the remaining 1 patient received azathiopurine alone. 71.7% of the patients achieved fistula closure, with a median follow-up of 32 months. Among the patients who received biologics as the initial treatment, 38.5% achieved fistula closure without the need for surgery, and 50% of the patients underwent surgery. Fistula closure was observed in 69.7% of the patients who underwent surgery as the initial treatment. Enteral nutrition before initial treatment was independently associated with fistula closure. Although surgery occupies a crucial role in the treatment of patients with non-perianal fistulizing CD, biologics are also effective. Enteral nutrition may increase the probability of fistula closure, especially in patients who undergo surgery as the initial therapy.

Background/Objectives: Limited data exist on the epidemiology and clinical management of short bowel syndrome (SBS) and chronic intestinal failure (CIF) in Crohn’s disease (CD). This study aimed to evaluate these aspects in Italy. Methods: Members of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) were invited to complete a cross-sectional web survey. A subgroup analysis examined the influence of different clinical settings on SBS and CIF management in CD. Results: A total of 47/128 (36.7%) IG-IBD centers participated. Among them, 31.9% were teduglutide (TED) prescribers, and 48.9% were academic centers. The median estimated prevalence of CIF among small bowel CD patients was 1%, and it was significantly higher in academic centers (2.0% [IQR 1–5%] vs. 0.13% [IQR 0–1%], p = 0.02). Seventy-eight percent of centers managed fewer than 10 SBS and CD patients. Routine small bowel measurement and nutritional assessment were performed in only 15% and 42.6% of centers, respectively. TED was prescribed by 12 centers to 35 patients, with a treatment success rate exceeding 50% in 81.8% of centers. Conclusions: The estimated prevalence of CIF in CD patients with small bowel involvement in Italy is 1%. The diagnosis and management practices for SBS and CIF are suboptimal, and TED use is limited.

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).

INTRODUCTION:There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch.METHODS:This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch.RESULTS:One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status.DISCUSSION:Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Crohn’s disease (CD) is an immune-mediated inflammatory bowel disease (IBD) with a multifactorial pathogenesis involving genetic predisposition, immune dysregulation, and environmental triggers. Dietary patterns have recently garnered growing attention for their potential benefits and risks in patients with IBD. Nutritional therapy has been established as an effective option in pediatric populations, but its role in adults remains less defined. The available studies indicate that while no single diet can be universally recommended, adherence to a Mediterranean diet is associated with multiple health benefits. Nutritional therapy appears promising in inducing clinical remission in adults with mild to moderate CD, particularly when partial enteral nutrition is combined with food-based modifications. Tailoring these strategies to cultural contexts and providing support from qualified dietitians may improve adherence, clinical outcomes, and overall quality of life. This review highlights the growing role of nutritional therapy in adult CD and its potential integration into routine management alongside conventional treatments.