Background: Real-world data on outcomes of patients with newly diagnosed Crohn’s disease (ndCD) is limited. We aimed to assess the achievement of corticosteroid-free clinical remission (CS-free CR) and other therapeutic targets 1 year after diagnosis in a cohort of patients with ndCD treated by a multidisciplinary team (MDT). Methods: A prospective observational cohort study was conducted on consecutive treatment-naïve adults with ndCD. Patients received management at the treating physician’s discretion, along with a tailored nutritional plan provided by an inflammatory bowel disease (IBD)-oriented dietitian. Patients were guided and educated by an IBD nurse, with flexible communication access to the IBD team. Therapeutic targets were assessed at 1 year. Multivariable logistic regression was used to evaluate predictors of CS-free CR. Results: Seventy-six patients (50% female) with a median age of 27 (22–39) years were eligible. Over 75% of patients were assessed by IBD-oriented dietitians and the IBD nurse. Within a median of 4.3 (2.5–6.7) months from diagnosis 60.5% initiated biologics (96% anti- tumor necrosis factor). Dietary intervention was applied to 77.6% of the cohort, either monotherapy (33.9%) or add-on (66.1%). At 1 year, 64.5% of patients achieved sustained CS-free CR, 56.6% biochemical remission, 55.8% endoscopic response, 44.2% endoscopic remission, 30.8% deep remission, and in 39.5% there was an improvement in health-related quality of life (HRQoL). Predictors for CS-free CR were uncomplicated phenotype (B1/P0), lower body mass index, and lower patient-reported outcome 2 scores at diagnosis. Conclusions: In a real-world setting at a tertiary medical center, a cohort of ndCD patients treated by an MDT resulted in favorable 1-year outcomes. Over 60% achieved CS-free CR, along with significant improvements in biomarkers and HRQoL.

Background: The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn’s disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16–22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. Results: Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16–22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). Conclusion: Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line.

INTRODUCTION: The gut microbiome in Crohn's disease (CD) shows variability and conflicting associations with disease activity. We aimed to assess microbial and clinical trajectories in newly diagnosed CD (ndCD) over 1 year. METHODS: This prospective longitudinal inception cohort study followed treatment-naive patients with ndCD for 1 year. The primary outcome was sustained corticosteroid-free clinical remission (CSFR) after 1 year. Paired fecal samples were collected at diagnosis and 1 year later, analyzed using bacterial 16S rRNA gene high-throughput sequencing. Microbial composition changes were compared between baseline and 1-year follow-up and between biologics-treated and conservatively managed patients. Fecal samples from healthy volunteers served as controls. RESULTS: Seventy-three patients participated; 64.4% achieved sustained CSFR after 1 year. During follow-up, 60.3% had moderate-to-severe disease activity and received biologics (95.5% anti-tumor necrosis factor), whereas 39.7% were managed conservatively. Significant microbial improvements, including increased Shannon diversity and decreased microbial dysbiosis index, were observed only in patients achieving sustained CSFR (both P < 0.001). Biologic-treated patients had more disrupted baseline microbiome composition than conservatively managed ones (Shannon, P = 0.04; microbial dysbiosis index, P = 0.03); they showed significant microbial improvement regardless of clinical success, shifting toward a healthier microbiome profile. Changes in clinical outcomes over 1 year correlated with microbial alterations. DISCUSSION: Over 1 year, treatment-naive patients with ndCD showed microbial improvements paralleling clinical outcomes, with shifts toward a healthier state. Biologic therapy enhanced microbial profiles, likely due to greater baseline disruption in these patients. These findings suggest that the microbiome is a marker of inflammation and a modifiable factor in CD management.

Background: Ocular manifestations (OMs) are recognized extraintestinal complications in inflammatory bowel disease (IBD), but their incidence remains understudied. We aimed to evaluate the incidence and trends of OM in a large population-based cohort of adults with newly diagnosed IBD over the past 2 decades. Methods: We conducted a retrospective cohort study including all adult-onset IBD patients between 2005 and 2024 in a large health maintenance organization. Patients with pre-existing OM diagnoses were excluded. The primary outcome was incident OM (uveitis, episcleritis/scleritis, or orbital inflammation) after IBD diagnosis. Annual incidence trends were assessed using the Cochran-Armitage test. Risk factors were analyzed via multivariable Cox regression, stratified by IBD type. Results: Among 15 035 newly diagnosed IBD patients (51.8% Crohn’s disease [CD], 48.2% ulcerative colitis [UC]), 349 developed an OM over 119 669 person-years (incidence: 2.9 per 1000 person-years; 95% confidence interval [CI], 2.62-3.24). OM incidence was higher in CD than UC (log-rank P < .001) and remained stable over time (P = .125). The median time to OM was 45 months. In CD, female sex (hazard ratio [HR], 1.62; 95% CI, 1.24-2.13) and systemic corticosteroid use (HR, 1.62; 95% CI, 1.18-2.22) were significant risk factors. In UC, corticosteroids (HR, 2.17; 95% CI, 1.40-3.37) and intestinal surgery (HR, 3.50; 95% CI, 1.69-7.28) were associated with increased OM risk. Conclusion: OMs in adult-onset IBD are infrequent but clinically relevant, particularly among CD patients and those with markers of severe disease. Clinician awareness and early referral remain essential for prompt diagnosis and management.

Background: Crohn’s disease (CD) incidence is rising in India. However, features of newly diagnosed patients with CD in this population are largely unknown. The Indo-Israeli IBD GastroEnterology paRtnership (TiiiGER) aimed to investigate differences in presentation among patients with newly diagnosed CD in India and Israel, and to explore phenotype–serotype correlations. Methods: A prospective observational cohort study of consecutive adults (>18 years) conducted in two large referral centers in India and Israel (2014–2018). Clinical data, an antiglycan serological panel, and 20 CD-associated genetic variants were analyzed. Outcomes: complicated phenotype at diagnosis and early complicated course (hospitalizations/surgeries) within 2 years of diagnosis. Results: We included 260 patients (104, Indian (65.4%, male; age, 37.8); 156 Israeli (49.4%, male; 31.8, age)). Median lag time from symptoms onset to diagnosis was 10.5 (IQR 3–38) vs. 3 (IQR 1–8) months in Indian vs. Israeli patients (p < 0.001). Complicated phenotype at diagnosis was observed in 48% of Indian and 30% of Israeli patients (p = 0.003). Complicated phenotype was associated with higher anti-Saccharomyces cerevisiae antibody (ASCA) seropositivity rate among Israeli patients (p < 0.001), but not among Indian patients. Antiglycan serology did not correlate with the tested genetic variants. Early complicated course occurred in 28 (18%) Israeli and 13 (12.5%) Indian patients. The time from diagnosis to complication was comparable (log rank p = 0.152). Antiglycan serology did not correlate with a complicated early course in either cohort. Conclusions: There are significant differences in patients presenting with newly diagnosed CD in India and Israel, including phenotype and distinct biomarkers at diagnosis. These differences suggest different genetic and environmental disease modifiers.