Ileocaecal resection versus infliximab for ileal Crohn's disease: retrospective 10-year follow-up of the LIR!C trial.

Crohn's disease (CD) in children poses a growing clinical challenge, with increasing incidence and variable response to biologic therapies such as infliximab (IFX). While gut bacterial dysbiosis has been extensively studied, the role of the gut virome in pediatric CD remains largely unexplored. This study provides the first longitudinal characterization of the fecal virome in children with CD undergoing IFX therapy. We reveal distinct viral community patterns, functional alterations, and virus-bacteria interactions in pediatric CD patients. Notably, integration of virome and bacteriome profiles enhances diagnostic accuracy, offering a promising avenue for predictive biomarker development. Furthermore, virome changes may be associated with the IFX treatment outcomes in children with CD. These findings highlight the gut virome as a critical but overlooked dimension of host-microbiome interactions in pediatric CD, with potential implications for personalized therapy and mechanistic understanding of treatment resistance.

Background/Objectives: Infliximab (IFX) is commonly used in chronic inflammatory conditions of the ileo-anal pouch. A subcutaneous (SC) formulation has been developed, with studies in inflammatory bowel disease (IBD) patients showing that switching from intravenous (IV) to SC IFX is safe with a low risk of relapse. However, so far, it has not been specifically investigated in chronic inflammatory pouch conditions. The aim of our study was to evaluate the effectiveness and safety of SC IFX in patients with chronic inflammatory pouch conditions. Methods: This was an observational retrospective study. We included patients with chronic inflammatory pouch conditions, initially treated with IV IFX and subsequently switched to SC IFX, who had a follow-up of at least 1 year. The primary outcome was SC IFX treatment persistence, defined as continuation of SC IFX throughout the study period. The secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results: A total of seven patients were included. The mean age was 50.6 years. The average follow-up length was 101.3 months (range 70.4-132.6 months). All seven patients continued SC IFX throughout the study period. No patient experienced pouch failure. The median IFX serum concentration was 18.1 mg/L. There were no cases of serious infections or malignancy. Conclusions: Switching clinically stable patients with chronic inflammatory pouch conditions from IV to SC IFX formulation appears feasible. These findings warrant confirmation in larger patient cohorts.

This study aimed to develop a predictive model for how patients with inflammatory bowel disease (IBD) respond to infliximab (IFX) treatment. One hundred adult IBD patients admitted to Shulan (Hangzhou) Hospital from August 2023 to November 2024 were included and divided into response and non-response groups based on their reaction to IFX. The response group consisted of 57 patients (57.0%), while the non-response group had 43 patients (43.0%). Clinical data, including gender, age, BMI, disease type (Crohn’s disease/ulcer-ative colitis), disease activity indices (CDAI/UCAI), history of IFX treatment, and infusion reactions, were collected and compared between the two groups. Additionally, biomarker levels, such as TNF-α, CRP, calprotectin, anti-infliximab antibody (ATI), IL -6, and IL -8, were measured during the midcourse of IFX treatment. Single-factor analysis identified variables that differed, and logistic regression showed that calprotectin level (OR=1.099, 95%CI=1.039-1.163), ATI (OR=3.756, 95%CI=1.222-11.546), IL -6 (OR=1.261, 95%CI=1.069-1.488), and IL -8 (OR=1.014, 95%CI=1.004-1.024) were key factors influenc-ing treatment response (p < 0.05). A nomogram was created using these fac-tors to predict treatment response in IBD patients. ROC analysis showed AUC values of 0.809, 0.762, 0.850, and 0.775 for calprotectin, ATI, IL -6, and IL -8, respectively, with corresponding 95% confidence intervals. The calibration curve indicated good model fit. These findings underscore the important roles of these cytokines in IBD pathogenesis and the action of IFX, as well as the high predictive power of the nomogram model.

Fulminant central demyelinating lesions associated with infliximab treatment in a child with Crohn's disease: A case report

To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.

BACKGROUNDLow drug concentrations have been linked to antidrug antibody (ADA) formation. High clearance is a major reason for low drug levels leading to treatment failure in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX).AIMTo explore the predictive value of initial IFX clearance on outcomes and assess the impact of Bayesian model (iDose)-guided IFX dosing on clearance and outcomes during induction and early maintenance treatment.METHODSData from a Phase 3 study of 220 CT-P13/originator IFX-treated patients with Crohn’s disease were used to develop probability models for outcomes including mucosal healing (MHEAL), biomarker response [C-reactive protein (CRP)], ADA development, a composite endpoint and time to first ADA formation, based on initial clearance. Subsequently, patients with characteristics suggesting rapid initial clearance were enrolled in a ≤ 120-day (October 2018 to December 2019) compassionate use program of iDose-guided IFX treatment as a proof of concept to determine if the probabilities from initial clearance could be improved with individualized therapy. Serial serum IFX concentrations, clearance, outcome probabilities, and treatment outcomes were analyzed.RESULTSIn the CT-P13 study, population pharmacokinetic was consistent with previously published models. Initial clearance was a significant predictor of several outcomes including MHEAL, CRP normalization, a compositeendpoint ((1) CDAI at week 54 was at least 150 points less than baseline; (2) MHEAL at week 54; (3) CRP was in normal range at week 54; and (4) FCP was less than 250 at week 54) and ADA formation. In the proof-of-concept study, 10 patients received iDose-guided IFX treatment. Initial clearance ranged from 0.017 L/day to 1.11 L/day, prompting up to three IFX infusions within the first 2 weeks. Two patients were discontinued due to ADA. Generally, clearance slowed over time and inflammatory biomarker levels improved. There were no adverse effects.CONCLUSIONInitial IFX clearance correlates with efficacy metrics and ADA formation. These probability curves may be useful to identify patients at risk of treatment failure or ADA who may benefit from individualized therapy. iDose-guided treatment successfully achieved targeted serum IFX concentrations, reducing risk of ADA formation. Proactive therapeutic drug monitoring and targeted dosing based on early IFX clearance may improve treatment outcomes for patients with IBD.

Specific human leukocyte antigen (HLA) genotypes, particularly HLA-DQA1*05, have been proposed as predictors for infliximab (IFX) treatment response and immunogenicity in Western populations. However, the evidence regarding the effect of HLA-DQA1*05 remains limited in East Asian populations, including in Japan. Moreover, HLA-DQA1*05 frequency differs substantially from those in Western populations. Comprehensive analyses of the association between HLA alleles and IFX treatment outcomes may contribute to the identification of novel prognostic markers for IFX therapies. We retrospectively analyzed 301 biologic-naïve Japanese patients with inflammatory bowel disease (IBD). IFX persistence was assessed at both 2-digit and 4-digit HLA allele resolutions, and associations with anti-drug antibody levels at 1year after the initiation of IFX therapy were evaluated. At the 2-digit resolution analysis, HLA-DQB1*03 (hazard ratio [HR] = 2.39, p = 1.89E-06) and HLA-DQA1*05 (HR = 1.99, p = 3.91E-04) were significantly associated with early IFX discontinuation. At the 4-digit resolution analysis, HLA-DQB1*03:01 (HR = 2.03, p = 9.42E-05) and HLA-DQA1*05:05 (HR = 2.18, p = 4.42E-05) showed similar associations. All HLA-DQA1*05:05 alleles formed haplotypes with HLA-DQB1*03:01. Importantly, HLA-DQB1*03:01 was also associated with early discontinuation of IFX even when it formed haplotypes with alleles other than HLA-DQA1*05:05. Both HLA-DQB1*03:01 and HLA-DQA1*05:05 were significantly associated with elevated anti-drug antibody levels (p = 3.23E-03 and 3.54E-03, respectively). HLA-DQB1*03:01 encompasses the information of HLA-DQA1*05:05 and serves as a strong genetic predictor of IFX treatment persistence and immunogenicity in Japanese patients with IBD, offering a potential biomarker for personalized therapy.

ABSTRACT Background While clinical trials have demonstrated that approximately 50% of patients with Crohn’s disease (CD) maintain clinical remission at 1 year with infliximab (IFX), the outcomes of long-term IFX treatment in CD are still under scrutiny. Research design and methods This retrospective cohort study analyzed 113 patients with CD from September 2010 to July 2025 to evaluate adherence and clinical remission rates, as well as to identify factors associated with treatment adherence. Results The median duration of IFX treatment was 61.7 months. At the 72-month follow-up (M72), patients were categorized into M72-remission (44.2%) and M72-non-remission (55.8%) groups. The M72-remission group had a significantly higher baseline Crohn’s disease activity index score than the M72-non-remission group (p = 0.003). However, this difference was no longer significant at the 72-month follow-up (p = 0.254). At the final follow-up, 67.3% of patients continued to receive IFX treatment. Both the adherence rate to IFX (p = 0.012) and the clinical remission rate (p = 0.030) were significantly higher in patients with no surgery compared to those with surgery prior to IFX treatment. Conclusions Early clinical remission was not associated with the adherence to IFX treatment. Previous surgery may be an independent risk factor for long-term IFX treatment failure.

Real-world data regarding subcutaneous infliximab (SC-IFX) in patients with pediatric inflammatory bowel disease IBD (PIBD) is scarce. We evaluated SC-IFX as maintenance therapy in PIBD patients who switched to SC-IFX from intravenous infliximab (IV-IFX) treatment. In this retrospective multicenter study we identified PIBD patients who switched to SC-IFX. The primary outcome was treatment persistence at up to 12 months post-switch. Secondary outcomes included relapse rate (defined as Pediatric Ulcerative Colitis Activity Index [PUCAI] ≥10/ weighted PCDAI ≥ 12.5 with biochemical/endoscopic evidence of disease activity), IFX trough levels, immunogenicity, safety, and acceptance. Sixty-six patients switched to SC-IFX (48% males; median switch-age, 16.5 years; IQR, 14.9-17.3 years; median switch-weight, 60 kg; range, 13-102 kg), 41/66 (62%) with Crohn Disease. Pre-switch, the median IV-IFX maintenance dose was 10 mg/kg every 6 weeks; 58/66 patients (88%) were in clinical remission. The initial SC-IFX regimen was 120 mg every other week in 62/66 patients (94%). SC-IFX persistence was 78% (95% CI, 66-91) at 12 months post-switch, with 89% of patients persisting on IFX, either intravenous (IV) or subcutaneous (SC), at the end of follow-up. Relapses were observed in 11/66 patients (17%) over a median follow-up of 11.0 months (IQR, 5.1-12.0); 6 patients underwent SC-IFX dose intensification, with 3 successfully regaining clinical response. Regarding anti-drug antibodies (ADA), 3 out of 4 patients who were ADA positive on IV-IFX resolved post-switch. Overall, 19/66 patients (29%) reported 21 adverse events (AEs), including 3/21 severe AEs. The majority (53/66 patients; 80%) expressed a positive attitude toward SC-IFX. The largest documented PIBD cohort switching to SC-IFX to date showed high treatment persistence at 1 year, confirming SC-IFX as an effective and safe maintenance alternative to IV-IFX.

Background: Inflammatory activity in rheumatoid arthritis can be determined by normal blood count ratios such as Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammation Index (SII), and C-reactive Protein (CRP). Objective: The aim of this research is to determine how these markers change after therapy and whether their pre- and post-treatment differences follow patterns that allow for simple parametric analyses. Methods: A prospective cohort of 52 RA patients (30 females and 22 males) was examined. The patients' blood samples were tested at baseline and at the end of their 6-month Infliximab treatment. Hematologic markers such as NLR, PLR, and SII were calculated from the complete blood count (CBC), and CRP levels were measured. The statistical methods of Shapiro-Wilk (SW), Kolmogorov-Smirnov (KS), and Anderson-Darling (AD) were used, and later, paired t-tests were used to generate statistics where necessary. Results: Post-treatment measurements were consistently lower for all four biomarkers. QQ-plots and formal tests revealed that the differences between findings were essentially normal, allowing for paired t-tests. The mean decreases were as follows: NLR -1.10 (95% CI -1.48 to -0.71), PLR -43.0 (-55.4 to -30.7), SII -299 (-388 to -211), and CRP -11.36 (-13.18 to -9.54), all p < 0.001. CRP showed the greatest drop, with significant decreases in PLR and SII and a moderate decline in NLR, indicating therapy-related attenuation of systemic inflammation. Conclusions: The study shows that six months of infliximab therapy results in a consistent post-treatment decrease in all four biomarkers: NLR, PLR, SII, and CRP. Because the pre-post differences were roughly normal, CRP revealed the greatest decrease, with significant decreases in PLR and SII and a moderate decrease in NLR, consistent with systemic inflammation reduction. When combined, the CBC-derived indices track with CRP and can serve as practical, low-cost markers for monitoring therapy response in RA, despite the single-arm design.

Abstract BACKGROUND In pediatric inflammatory bowel disease (IBD), proactive therapeutic drug monitoring (TDM) involves measuring infliximab (IFX) trough levels at pre-specified time points or intervals. Existing literature suggests that optimizing IFX dosing in response to levels at week 14, prior to the start of maintenance infusions, offers clinical benefit at 52 weeks. There has been growing interest in beginning proactive TDM earlier, prior to the 3rd and final induction infusion. We hypothesize that early proactive TDM prior to the 3rd versus 4th IFX infusion improves clinical outcomes in children with IBD. METHODS A retrospective cohort analysis included children with IBD receiving IFX treatment between January 1, 2020 and December 31, 2023. This study compared patients who underwent proactive TDM of IFX prior to the 3rd infusion (early group) versus those whose levels were first measured prior to the 4th infusion (later group). Propensity score matching was used to match patients based on gender, disease, and age at IFX start. Clinical and laboratory data, along with Physician Global Assessment (PGA), were collected at baseline and for one year following initiation of IFX and compared between the early and later groups. The primary outcomes were time to clinical remission based on PGA and therapeutic maintenance IFX levels (&amp;gt;5 μg/ml), IBD-related hospitalizations and surgeries, and discontinuation of IFX. Secondary outcomes evaluated clinical outcomes at 6- and 12-months post-IFX initiation in both groups. Time to event analysis including Kaplan Meier plots and log-rank tests were used to compare time to therapeutic maintenance between study groups. RESULTS In total, 68 patients from each group were matched. Patients from the early group experienced a faster median time to clinical remission of 140 days (95% CI: 108, 167) versus 203 days (95% CI: 167, 232) in patients from the later group (p &amp;lt; 0.05). While time to therapeutic maintenance IFX levels did not significantly differ across the entirety of both groups, 75% of patients from the early group achieved therapeutic levels in a median of 134 days (95% CI: 114, 182) versus 183 days (95% CI: 153, 224) in the later group. There were no significant differences in IFX discontinuation, hospitalizations, IBD-surgeries, or clinical outcomes at 6- and 12-months post-IFX initiation between the groups. CONCLUSIONS Early proactive TDM of IFX prior to the 3rd infusion may significantly accelerate time to clinical remission compared to later proactive TDM. It is suspected that measuring IFX trough levels earlier prior to the third infusion enables timely dose adjustments and promoted faster clinical improvement. Given its potential to enhance outcomes, early proactive TDM prior to the third infusion should be considered a valuable strategy in the clinical management of children with IBD.

IntroductionChronic exogenous exposures related to perianal fistula care may lead to systemic effects in patients with Crohn’s disease and require a multisystemic evaluation. In this case, we aimed to raise awareness by presenting a rarely encountered treatment-related complication in a patient with Crohn’s diseaseClinical CaseA 22year-old female with history of ileocolonic, fistulizing Crohn’s disease had previously undergone right hemicolectomy and enterovesical fistula repair. The patient, who had prior exposure to adalimumab and ustekinumab, was most recently on upadacitinib, which had been discontinued 2 months earlier due to the development of a perianal fistula under treatment. Because of recurrent perianal fistulas, she had been under follow-up by general surgery. She was admitted to the gastroenterology clinic for further evaluation due to anal pain and elevated acute phase reactants.On admission, physical examination revealed complaints of hot flashes, sweating, and hand tremors. Tenderness in the perianal region and an active fistula tract were observed. Laboratory tests showed CRP 124 mg/L, TSH <0.01 mIU/L, fT3 >30.80 pmol/L, and fT4 >154.80 pmol/L. Thyroid ultrasonography(USG) was normal, while Tc-99m pertechnetate uptake was measured at 0.15% with a scintigraphic pattern reported as “compatible with exogenous iodine exposure/thyroiditis.” Thyroid antibody profile was negative. Spot urine iodine was 57 µg/L. Upon re-evaluating the history, it was learned that the fistula tract had been irrigated regularly with povidone-iodine for the past three months. With elevated urinary iodine levels and regular povidone-iodine exposure, the patient was diagnosed with iodine-induced thyrotoxicosis.Endocrinology consultation recommended initiation of methimazole 30 mg/day and propranolol 20 mg twice daily, with beta-blocker dose titrated according to symptoms. The patient was monitored daily for thyroid storm.Corticosteroid therapy was not initiated due to the presence of active perianal fistula and abscess. During this period, infection control was achieved with parenteral antibiotics, surgical drainage and seton placement, as well as initiation of infliximab therapy.The patient achieved control of the perianal infection, and Infliximab treatment was given for Crohn's. With antithyroid and symptomatic treatment, thyrotoxic manifestations were stabilized.ConclusionThis case demonstrates that chronic exogenous iodine exposure during perianal fistula care in Crohn’s disease may lead to systemic thyroid dysfunction. In the literature, iodine toxicity has been reported to cause various thyroid disorders. For the diagnosis; thyroid function tests, spot urinary iodine measurement, and thyroid scintigraphy are of particular importance. In conclusion, systemic effects of iodine-containing antiseptics used during perianal fistula care in Crohn’s patients should be carefully considered, and thyroid functions should be monitored regularlyTable 1:Follow-up of the patient's thyroid function test results

Background/Objectives: There is limited data regarding the association of anti-drug antibody (ADA) levels with the efficacy of anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). We aimed to investigate the association between antibody to adalimumab (ATA) and antibody to infliximab (ATI) levels and treatment failure in IBD. Methods: This single-center, retrospective cohort study included consecutive IBD patients with ADA evaluated with a drug-tolerant assay between September 2012 and February 2023. A time-to-event analysis was performed for treatment failure, defined as the need for drug discontinuation due to primary non-response, loss of response, a serious adverse event, or an IBD-related surgery. Patients were followed from first positive ADA until treatment failure or the end of the follow-up (May 2024). Results: The study population consisted of 134 patients with IBD [n = 58 (43%) on adalimumab; n = 86, (64%) with Crohn’s disease]. Multiple COX regression analysis identified higher ADA levels to be associated with treatment failure (HR: 1.034, 95%CI: 1.024–1.045, p < 0.001). A ROC analysis identified an ATA and ATI level threshold of 5.2 U/mL (AUC: 0.705; 95%CI: 0.569–0.841; p = 0.003; sensitivity: 64%; specificity: 82%) and 8.8 U/mL (AUC: 0.809; 95%CI: 0.713–0.906; p < 0.001; sensitivity: 69%; specificity: 93%), respectively, to distinguish patients with or without treatment failure. Conclusions: In this large retrospective cohort study, higher levels of ADA were associated with treatment failure to anti-TNF therapy in IBD. Moreover, we identified ATA and ATI level thresholds of 5.2 U/mL and 8.8 U/mL, respectively, to be associated with treatment failure.

The early prediction of secondary loss of response (SLOR) after infliximab (IFX) treatment in Crohn's disease (CD) patients can help optimize treatment strategies. This study developed and validated a multimodal deep learning model that uses baseline endoscopic ulcer lesions to predict SLOR. Additionally, a deep learning-based ulcer detection model was established to automatically identify ulcer lesions. A total of 385 CD patients from three centers were retrospectively analyzed. An ulcer detection model was developed to identify endoscopic ulcer lesions from 12,092 endoscopic images. Following lesion localization, 2189 ulcer images were selected and used to train feature fusion models, while clinical data were incorporated to construct a multimodal model for SLOR prediction. These models were validated in two external test cohorts. The ulcer detection model achieved precision values of 0.853 in the validation cohort. The multimodal model outperformed the clinical model in predicting SLOR with areas under the ROC curve (AUCs) of 0.892, 0.847, and 0.824 in the internal validation cohort, external test cohort 1, and external test cohort 2, respectively. Gradient-weighted class activation mapping (Grad-CAMs) revealed highly pronounced activation of the ulcerated area in SLOR patients in the model, providing crucial support for model prediction. The ulcer detection model effectively identifies ulcer lesions, increasing diagnostic efficiency. The multimodal model, which integrates baseline endoscopic images and clinical data, offers a potential tool for early SLOR prediction.

Abstract Background To investigate the clinical characteristics of Ulcerative colitis (UC) patients receiving Infliximab (IFX) or Vedolizumab (VDZ) treatment, as well as the risk factors for concurrent Clostridium difficile infection (CDI). Methods Patients hospitalized in the Department of Gastroenterology, Shengjing Hospital of China Medical University, who were clearly diagnosed with UC and received IFX or VDZ treatment between January 2019 and May 2025 were enrolled in this study. Data collected included patients’ general information, laboratory test results, disease-related data, information on combined medication use within 2 months before admission, and therapeutic medications for patients with CDI during hospitalization. The clinical characteristics of the patients were analyzed, and the risk factors for CDI in the patients were identified. Results A total of 110 patients with UC were enrolled in this study. The positive rate of Clostridioides difficile (C. diff) was 28.2%, among which the CDI rate was 23.6% and the C. diff colonization rate was 4.5%. Results of univariate logistic analysis showed that a positive purified protein derivative (PPD) test, concurrent Epstein-Barr virus (EBV) infection, a modified Mayo score ≥11 points, and a history of hormone use within 2 months before admission were associated with an increase the risk of CDI; For UC patients receiving IFX or VDZ treatment, concurrent CDI were associated with fever or prolonged hospital stay (all P &amp;lt; 0.05). Multivariate logistic regression analysis revealed that concurrent EBV infection, a modified Mayo score ≥11 points, and a history of hormone use within 2 months before admission were likely independent risk factors for concurrent CDI in UC patients treated with IFX or VDZ (P &amp;lt; 0.05). Indication of inter-group comparison: in the IFX group, the C. diff positive rate was 23% and the infection rate was 18%; in the VDZ group, the C.diff positive rate was 34.7% and the infection rate was 30.6%. But no statistically significant differences were observed in the positive rate or infection rate between the two groups (positive rate: P = 0.174; infection rate: P = 0.123). Analysis of the onset time of CDI in patients from both groups indicated that among UC patients who initiated biological agent (VDZ/IFX) treatment, the proportion of CDI cases occurring within 0-3 months was the highest, but this difference was not statistically significant. Conclusion Concurrent EBV infection, a modified Mayo score ≥11 points, and a history of hormone use within 2 months before admission may be independent risk factors for CDI in UC patients receiving IFX or VDZ treatment. Conflict of interest: Xu, Tingting: No conflict of interest Tian, Feng: No conflict of interest Xie, Ying: No conflict of interest

Abstract Background The gut microbiota has been implicated in the pathogenesis of Crohn’s disease (CD), and infliximab (IFX) is commonly being utilized as a therapeutic option for pediatric CD patients. However,it remains unclearwhether the fecal virome is modified during IFX treatment. This study aims to characterize the alterations in the fecal virome among pediatric patients with CD and to evaluate how IFX therapy affects these changes. Methods Metagenomic sequencing of fecal viral-like particles was applied todetermine the compositions of virome communities in fecal samples. The composition and function of the fecal virome were compared between CD patients(n = 60) and healthy controls(n = 25). Among these patients, 53 received at least three IFX treatments,and 41 of them achieved remission (IFX-R), while 12 did not (IFX-NR). Results Compared with controls, CD subjects exhibited significantly lower viral richness (measured by the Chao1 index). Patients in the baseline CD remission group (Baseline-R) demonstrated significantly elevated linear discriminant analysis (LDA) scores for Anelloviridae compared to other subjcets. Conversely, Microviridae manifested higher LDA scores in healthy control subjects, while Caudovirales displayed elevated LDA scores at the baseline level of the non-remission group (Baseline-NR). Following treatment with IFX, the IFX-R group exhibited a more diverse composition of dominant viral taxa, indicating potential remodeling of the gut virome during remission. Additionally, CD patients exhibited differences in various viral functions in terms of Gene Ontologyfunctions compared with healthy controls. Moreover, the combined fecal virome and bacterial markers demonstrated diagnostic potential for CD, with AUC of 89.3%. Conclusion Fecal virome in pediatric CD is characterized by a significant decrease in fecal viral diversity, changes in specific virus taxa, and a loss of multiple viral functions. Certain patterns in the fecal virome and fecal microbiome may be predictive for diagnosis of pediatric CD. Conflict of interest: Ge, Ting: No conflict of interest Ruan, Yangming: No conflict of interest Ye, Lin: No conflict of interest Xiao, Fangfei: No conflict of interest Prof. Dr. Zhang, Ting: No conflict of interest

Abstract Background This study aimed to describe the occurrence of adverse events (AEs) among individuals with inflammatory bowel disease (IBD) treated with infliximab (IFX) and to compare the risk of infection between those receiving biosimilar (IFX-B) versus originator (IFX-O). Methods Prospective and retrospective data on individuals with Crohn’s disease (CD) or ulcerative colitis (UC) who initiated IFX-B or IFX-O between 2018 and 2024 were obtained from seven IBD clinical centres contributing to CAN-AIM’s pan-Canadian clinical registry of biosimilar/bio-originator users. Participants were followed from IFX initiation until death, or last visit before discontinuation/switching, whichever came first. AEs occurring during infliximab treatment were summarized by affected organ system and severity (mild, moderate, or severe, as assessed by the treating physician). Incidence rates (IRs) of infection (per 100 person-years [PY], with 95% confidence intervals [CI]) were estimated, comparing IFX-B versus IFX-O. Multivariate hazard regression assessed time to first infection, comparing IFX-B versus IFX-O. The model was adjusted for sex, age, IBD type (CD or UC), IBD duration, prior/current corticosteroid use, and prior use of other biologics. Results A total of 208 individuals (117 CD, 91 UC) were included; 49% were female, and the mean age at infliximab initiation was 40 years. Most (75%) were biologic-naïve, and 58% started on IFX-B (Table 1). Overall, 232 AEs were reported among 108 individuals, most frequently infections (28%), gastrointestinal disorders (including nausea and abdominal pain, with 9%), and skin/subcutaneous tissue disorders (including rash and local skin reaction, with 17%). Approximately 10% of AEs were classified as severe. Over a median follow-up of 1.7 years (interquartile range 0.6–4.0), 33 individuals experienced a first infection, corresponding to an overall IR of 5.3 events/100 PY (95% CI 3.8–7.4). The IR was 10.6 (95% CI 6.7–16.9) among IFX-B users and 3.3 (95% CI 2.0–5.5) among IFX-O users. No significant difference in the adjusted hazard ratios (aHRs) were observed when comparing IFX-B versus IFX-O (aHR 1.84 (95% CI 0.74-4.55). Conclusion In this multicentre Canadian cohort of IBD patients treated with infliximab, infections were the most frequently reported adverse events. Despite numerically higher crude infection rates among IFX-B users, adjusted analyses were unable to demonstrate a significant difference in the risk of infection between infliximab biosimilar and originator users. Conflict of interest: Moura, Cristiano S: No conflicts Berger, Claudie: I have no conflict of interest. Lukusa, Luck: N/A Singh, Harminder: Harminder Singh has been on advisory boards or consulted for Pendopharm, Amgen Canada, Abbvie Canada, Pfizer Canada, Organon Canada, Takeda Canada, Innomar Strategies, Eli Lily Canada and Guardant Health, Inc consulted for the Canadian Agency for Drugs and Technology in Health has received research funding for an investigator-initiated study from Pfizer and holds shares of VasCon. recieved educational grants from Pfizer Canada, Organon Canada in kind research funding from Pendopharm Narula, Neeraj: Grant: Takeda, Pfizer, Abbvie Personal Fees: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Sandoz, Iterative Health, Innomar Strategies, Fresinius Kabi, Viatris, Celltrion, Organon, Eli Lilly, Ferring Non-financial Support: Abbvie, Janssen, Takeda, Pfizer, Ferring Targownik, Laura: Dr. Targownik reports personal fees and non-financial support from Abbvie Canada, personal fees and non-financial support from Johnson+Johnson Innovative Medicine, personal fees from Takeda Canada, personal fees from Amgen Canada, personal fees from Merck Canada, personal fees from Organon Canada, personal fees from Pfizer Canada, personal fees from Lilly Canada, personal fees from Bristol Myers Squibb Canada, outside the submitted work . Leung, Yvette: Dr. Leung reports personal fees and other from cellltrion, personal fees from abbvie, personal fees from janssen, personal fees from eli lilly, personal fees from takeda, non-financial support from takeda, non-financial support from pfizer, personal fees from pfizer, outside the submitted work . Zezos, Petros: None Polewiczowska-Nowak, Beata: Nothing to disclose. Baumgart, Daniel C.: Past 12 Months. Scientific Advisory Boards: AbbVie, Alfasigma, Eli Lilly Fresenius Johnson &amp; Johnson Pfizer Roche Takeda. Travel Support: Afa Sigma, AbbVie, Eli Lilly, Johnson &amp; Johnson Pfizer, Takeda. Education or Research Grants: AbbVie, Alfasigma, Amgen, AstraZeneca, Boston Scientific, Biogen, Canon Medical Systems, Celltrion, Dr. Falk, Ferring, Fresenius Kabi, Gilead Sciences, Ipsen, Janssen-Cilag GmbH (Johnson &amp; Johnson), Lilly. Nestlé Health Science, Pfizer. Afif, Waqqas: Grant: Abbvie, Takeda, Pfizer, Janssen Personal Fees: Advisory Boards: Abbvie, Amgen, BMS, Eupraxia, Eli-Lilly, GSK, Janssen, Innomar, Merck, Pfizer, Sandoz, Sanofi, Takeda Dr. Bernatsky, Sasha: No conflict of interest

Abstract Background Patients (pts) with Crohn’s disease (CD) or ulcerative colitis (UC) receiving infliximab (IFX) may undergo a treatment interruption (‘drug holiday’) for clinical or non-clinical reasons.1,2 Upon disease recurrence, reinitiating IFX intravenously (IV) may be considered with caution, but there are no data on starting subcutaneous (SC) IFX treatment after a drug holiday. This analysis evaluated the efficacy and safety of starting IFX SC in pts randomised to the placebo (PBO) maintenance arm in the Phase 3 LIBERTY studies who had previously completed IFX IV induction and subsequently experienced a ≥ 16-week drug holiday before starting IFX SC due to disease progression. Methods In LIBERTY-CD and -UC, responders to IFX IV induction were randomised at Week (W) 10 to receive either IFX SC 120 mg or PBO every other week up to W54.3 From W22, pts could receive IFX SC 240 mg through W102 if they lost response or at physician’s discretion. Data were aligned to IFX SC start (time zero). Clinical, biochemical, and endoscopic endpoints, treatment persistence, serum IFX levels, immunogenicity, and treatment-emergent adverse events were evaluated throughout the treatment period. Multivariable regression was used to identify potential predictors of response following IFX SC start in 51 CD and 77 UC pts from the PBO arms. Results The median (IQR) time from the last IFX IV induction to IFX SC start was 16 (16–24) weeks in both CD and UC. Early clinical responses were observed by 8±2 weeks after IFX SC start and maintained throughout the study (CD, 92.3%; UC, partial clinical response, 96.6%). Faecal calprotectin remission and endoscopic response/improvement were achieved in 61.1%/64.0% of CD and 65.2%/68.8% of UC, respectively, at the end of treatment. Persistence at treatment end was 72.3% in CD and 61.9% in UC. Serum IFX levels notably increased after IFX SC initiation compared to preinitiation trough levels and remained stable through W102. Among pts who were ADA-positive prior to IFX SC start, 68.2% (CD) and 61.9% (UC) remained on therapy through study end, compared with 83.6% and 50.0% of ADA-negative pts, respectively. In CD, predictors of clinical remission at 24±2 weeks after IFX SC start included clinical remission at W10 and IFX ≥20 μg/mL at 16 weeks after IFX SC start. In UC, predictors of partial clinical remission at 40±2 weeks after IFX SC start included lower partial Mayo score at W10, lower C-reactive protein at IFX SC start, and IFX ≥22 μg/mL at 8 weeks after IFX SC start. No significant safety concerns were observed after IFX SC start. Conclusion IFX SC 240 mg restored and maintained response in most CD and UC pts with sustained efficacy, safety, and persistence through W102. Early remission and higher IFX levels predicted success.

Abstract Background Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial chronic inflammatory disorder driven by dysregulated immune-microbiota interactions. Response to targeted therapies such as anti-TNF varies widely, with nearly one-third of patients failing to achieve remission. This variability not only affects patient outcomes but also leads to high costs and risks due to unnecessary drug exposure. Therefore, it is critical to identify early factors or biomarkers that can predict treatment response at an early stage. While early blood-based predictors have been studied, the role of the gut microbiome in early therapeutic outcomes remains unclear. In this work, we aim to identify early taxonomic and metabolic functions as potential biomarkers of remission in UC and CD patients treated with infliximab. Methods Metagenomic sequencing was performed on stool samples collected from 85 IBD patients (47 UC, 38 CD) enrolled in the GUIDE-IBD Clinical trial cohort at weeks 0, 2, and 14 of anti-TNF (infliximab) treatment. First, we characterized longitudinal microbial diversity and community composition. Then, a differential abundance analysis using mixed-effect linear models allowed us to identify taxa associated with different remission calls at week 14 (Clinical, Endoscopic, and Biochemical remission). Results At baseline, UC patients who achieved remission at week 14 showed lower microbial diversity compared to non-remitters, but alpha diversity increased by week 2, approaching the profiles of healthy-like microbiota by week 14 (Shannon index p &amp;lt; 0.05). This trend in alpha diversity was not observed in CD individuals. In addition, beta-diversity analysis confirmed distinct compositional trajectories between remitters and non-remitters (PERMANOVA F = 5.18, p = 0.00009) in both CD and UC. Overall, early enrichment of butyrate-producing taxa, including Faecalibacterium group (F. prausnitzii, F. duncaniae, F. intestinalis), Blautia sp., and Odoribacter splanchnicus, characterized remitters at baseline, whereas non-remitters showed dominance of proteobacteria taxa such as Mesosutterella massiliensis. This was reflected by the enrichment of metabolic functions in relation to SCFA synthesis and branched-chain amino acids, which are known to support intestinal homeostasis. Conclusion Our longitudinal metagenomic analysis shows that the early increase of short-chain fatty acid-producing bacteria during anti-TNF is a hallmark of successful therapy. These microbial changes precede clinical improvement, highlighting their potential as early, non-invasive biomarkers to guide therapeutic decision-making in IBD. Conflict of interest: Dr. Lopez Agudelo, Victor Alonso: No conflicts Tran, Florian: Grant: Sanofi/Regeneron Personal Fees: Speaker’s fees: Abbvie, Bristol-Myers-Squibb, Celltrion Healthcare, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, J&amp;J, Sanofi, Takeda Consulting honoraria: AbbVie, J&amp;J, Takeda Non-financial Support: Sanofi for statistical analysis Florea, Marina: Takeda Pharma Vertrieb GmbH, Abbvie, Dr. Falk Pharma, Galapagos Biopharma Germany GmbH/Alfasigma, Janssen Pharmaceutica Wiestler, Miriam: Financial compensation for lectures, advisory boards, other medical-scientific services by: AbbVie, Alfasigma, CED Service, Dr. Falk Pharma, FomF Forum für medizinische Fortbildung, FORUM Institut für Management GmbH, Johnson &amp; Johnson, Lilly Deutschland GmbH, Pfizer, Takeda Pharma. Rühlemann, Malte: No conflicts Moitinho E Silva, Lucas: No conflicts Groussin, Mathieu: No conflicts Waschina, Silvio: No conflicts Wacker, Eike Matthias: No conflicts Meneses, Rui: No conflicts Verspecht, Chloë: No conflicts Reniers, Iris: No conflicts Ekhlas, Daniel: No conflicts Raes, Jeroen: JR has received grants from Beneo, Cargill, Colruyt group, Danone, DSM, J&amp;J, MRM/Prodigest, Nestle, Pfizer, Takeda and VectivBio and has received consulting and/or speaking fees from Aphea, Biofortis, DSM-Firmenich, Ferring, GSK, Janssen Pharmaceuticals, Metagenics, MSD, MRM/Prodigest, Nutricia, Takeda, Tsumura Huber, Samuel: SH received personal compensation and fees for lectures and consultations as well as travel costs from Janssen Cilag, AbbVie, Ferring, Falk Foundation, Galapagos, Lilly, Bristol-Myers Squibb, and Ardeypharm GmbH Seidler, Ursula: No conflict of interest Aden, Konrad: Personal Fees: Lecture fee: Takeda, Janssen, Lilly, Abbvie Consulting fee: Takeda, Jannsen, Lilly, Guidepoint Schreiber, Stefan Wolfgang: Personal Fees: AbbVie, Alfasigma, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Celltrion, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Protagonist, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Rosenstiel, Philip: stock ownership Gerion