anti-TNF Therapy Research Articles

P535 Effectiveness of upadacitinib in patients with Ulcerative Colitis: a real-life, multicenter, Italian report

Abstract Background Upadacitinib (UPA) is an oral, selective JAK inhibitor, that has recently received approval in Italy for the treatment of Ulcerative colitis (UC). To our knowledge, only few data of real-life studies are available. The aim of our observational data collection is to report the first real-life experiences with UPA in UC in terms of effectiveness and safety. Methods These data come from four Italian IBD centers. Adult patients with a diagnosis of UC, who have been prescribed UPA for active disease, after failure of at least one anti-TNF therapy, were enrolled. After an induction period of 8 weeks with a 45 mg daily dosage, treatment efficacy were assessed using the partial Mayo score (pMS) and the fecal calprotectin levels (CP). Treatment-related adverse events were also recorded. Results Among 20 patients who started UPA, 12 have completed the induction and were therefore enrolled and evaluated before starting UPA and at the end of the 8 weeks induction period. 83% (10 patients) had previously failed two or more biological therapies, including tofacitinib (3 patients, 25%). 3 patients (25%) were tapering systemic corticosteroids and 3 patients (25%) were receiving topical steroids when they started UPA. In the pre-treatment evaluation, the mean pMs was 5,25 (SD 2,26) and the median CP was 1270 ug/g (411- 3152). At the end of induction (week 8), 10 patients (83%) achieved clinical remission and one patient showed clinical response with a decrease of 6 points of pMS. One patient underwent colectomy after 4 weeks of ineffective therapy. The mean pMS at week 8 was 0 (SD 0,92) (Fig. 1), with a median CP of 88 ug/g (5-4639). Reported adverse events, that however did not cause drug discontinuation, were one case of leukopenia and one case of acne. To the date of the last evaluation, all patients maintained the achieved results, with a mean follow-up period of 92 days. A further analysis excluding the physician global assessment from pMS has been performed, to obtain a sort of patient-reported outcome 2 (PRO-2): the results, in terms of percentage reduction of the scores, were in line with the presented data. Despite the limited number of patients who completed the induction (11), we observed statistical significance in the difference between pretreatment and post-induction values of all the measured variables (Tab. 1, Fig. 1). Conclusion With this first Italian report in a real-life setting, UPA showed promising effects in rapidly inducing clinical remission and in normalizing a sensitive marker of intestinal inflammation. Moreover, it seems to be well tolerated. Long-term real-life studies, including endoscopic and histologic evaluations, are needed to confirm efficacy and safety of UPA in maintaining stable remission in UC patients.

OP04 Endoscopic healing in paediatric IBD perpetuates a persistent signature characterized by pathogenic Th17 cells and tissue-associated molecular and microbial drivers of disease

Abstract Background Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBD) in adults and paediatric patients. However, EH may not represent disease clearance. Hence, risk of relapse remains high and treatment discontinuation after reaching EH often results in disease exacerbation. We aimed to identify persistent cellular, molecular and microbial drivers of IBD under EH and longitudinally collected endoscopic biopsies from paediatric patients for analysis of single T-cell and bulk transcriptomics as well as mucosa-associated microbiota. Methods We followed disease trajectories of paediatric IBD patients treated according to international guidelines and collected mucosal biopsies from the terminal ileum (TI) and sigmoid colon (SC) at baseline (T1) and after approximately 3-12 months (T2) to assess EH. Non-IBD controls showed no macroscopic or histologic signs of inflammation. Host RNA and bacterial DNA were simultaneously extracted from single biopsies for bulk RNA-seq, and 16S rRNA seq. A second biopsy was used for isolation of lamina propria mononuclear cells (LPMCs), followed by CD45+, CD3+ cell sorting and single T-cell analysis (10X Genomics). Data were quality controlled and integrated. Results 217 biopsies (135 simultaneous extraction of host RNA and bacterial DNA; 82 single T-cell analysis) from 32 paediatric IBD patients (mean age 13 ± 3.5 years, 21 Crohn’s disease [CD], 11 ulcerative colitis [UC]; T1 = 32, T2 = 32, T > 2 = 6) and 5 non-IBD controls were analysed. Time between T1 and T2 averages 40 ± 22 weeks. At baseline, 15 patients (14 CD, 1 UC) were newly diagnosed and 31/32 patients had active mucosal inflammation. Twenty-two patients (71%) achieved EH at T2 (SES-CED ≤2 and absence of ulcerations), mostly on anti-TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. In the bulk RNA-seq, we identified 299 differential expressed genes (DEGs; corrected p-value <0.05, FC >2.0), such as DUOX2, SAA2-SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non-IBD controls. In addition single cell analysis revealed an IBD-specific pathogenic Th17 cluster that continued to exist in EH and showed high correlation with top DEGs after data integration. 16S rRNA gene seq highlighted highly individual mucosa-associated bacterial profiles and a reduced α-diversity in active and EH compared to non-IBD controls. Conclusion A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity in comparison to non-IBD controls despite EH and mucosal regeneration. These markers may provide targets for future or sequential therapies.

P632 Isolation of a novel metalloproteinases transcriptional signature with robust anti-TNF therapy predictive power in patients with Ulcerative Colitis

Abstract Background Anti-TNF agents were the only biologic for Inflammatory Bowel Disease (IBD) patients. However, new drugs targeting α4β7 integrin, IL-12/IL-23, and janus kinases were added to the IBD therapeutic armamentarium. Anti-TNFs are first-line biological agents in our country, and for that reason, the discrimination of patients who will be refractory of those therapies before treatment is relevant to prevent IBD patients from the exposition to multiple therapeutic failures. Therefore, we wanted to isolate robust and reproducible transcriptional markers able to specifically predict the response to anti-TNF therapy, which will contribute to targeted prevention, improve individual outcomes and decrease therapy expenditures. Methods We analysed publicly available microarray and RNAseq datasets of colon biopsies (GSE12251, GSE16879 and GSE73661) and whole blood cells from different cohorts of patients with Ulcerative Colitis (UC) (GSE191328). R package was used to perform the differential expression analyses and calculation of receiver operating characteristic (ROC). Cytoscape software and Morpheus (broadinstitute.org) was used to perform network data integration and visualization. Also, we used our local cohort of UC patients to further validate our results by RT-qPCR (n=21). Results We isolated a transcriptional signature composed of eight metalloproteases (MMPs) with high association with disease activity. Most of the transcripts of that signature were significantly upregulated in colon biopsies of non-responder patients to anti-TNFs before treatment in three different microarray datasets, but not in vedolizumab-treated patients. ROC curves of the different MMPs showed variability in the correlation to anti-TNF response among the different datasets analysed. Only three out of eight MMPs were still showing robust predictive power with an area under the curve around of 80% when all dataset were combined. Interestingly, PBMCs isolated from our local cohort of IBD patients presented increased expression of those MMPs in refractory patients to anti-TNF therapy, confirming that these three MMPs have the highest predictive power both in colon tissue and in peripheral mononuclear cells. Conclusion Overall, our study revealed a novel and robust MMP-transcriptional signature associated with anti-TNF but not vedolizumab therapy response. Nevertheless, our results should be corroborated in independent cohorts of patients with UC to test their efficacy and sensitivity in the clinical setting. Our data definitively contribute to the change from a reactive approach to predictive, preventive and personalised medicine.

P852 Metataxonomic and metabolomic profiling to predict response to anti-TNF therapy in Crohn’s Disease

Abstract Background The composition of the gut microbiota is associated with response to treatments in inflammatory bowel disease1. We sought to identify gut microbial and metabolomic biomarkers associated with response to anti-TNF therapy in Crohn’s disease. Methods Faecal and serum samples collected at baseline and week 14 of anti-TNF treatment in the "Predictors of anti-TNF treatment failure" (PANTS) study were used2. Response to treatment (defined clinically and biochemically) was determined at week 142. Faecal samples were processed by GA-map®, with targeted 16S rRNA PCR sequencing. Serum samples were analysed with targeted liquid chromatography tandem mass spectrometry for bile acids and tryptophan metabolites. Multivariate and univariate analyses, as well as Spearman’s rank test, were performed. Results Two-hundred and twenty-four patients with Crohn’s disease commencing anti-TNF therapy were included (54.1% anti-TNF responders, 48.6% female, median age 37.2 (26.5-50.0) years, 56.9% receiving immunomodulator-based treatment). A significantly higher proportion of non-responders received corticosteroid treatment compared to responders at baseline (p=0.0009). Sixty-nine bacterial taxa were identified. Significantly lower abundances of Clostridium difficile and Mycoplasma were identified in responders relative to non-responders at baseline (q-value=0.046 and q-value=0.034, respectively). No significant differences in the abundances of Faecalibacterium prausnitzii, Shigella or Escherichia Coli were found (all q-values > 0.05). Eighteen serum bile acids and thirteen tryptophan metabolites were identified. Significantly higher serum abundances of cholic acid, tryptophan and 3OH-kynurenine were identified in responders at baseline (q-values=0.049, 0.033, and 0.033, respectively). Exploration of microbial–metabolite associations revealed negative correlations between secondary bile acids and several bile salt hydrolase producing bacteria, such as Bifidobacterium (r ≤ -0.50). Positive correlations were also identified between xanthurenic acid and Bifidobacterium and Roseburia intestinalis (r ≥ 0.50). Increased abundances of short-chain fatty acid producing bacteria, such as Bifidobacterium and Bacteroides vulgatus, were noted in responders at week 14. Conclusion We have identified baseline differences in the faecal microbiota and serum metabolome of anti-TNF responders and non-responders. These findings require validation in larger cohorts to determine their robustness for potential use in treatment personalisation.

P020 Effects of Anti-TNF Treatment on Browning of Mesenteric Adipose Tissue with Crohn's Disease

Abstract Background Crohn's disease (CD) is characterized by the expansion of mesenteric fat, known as creeping fat (CrF), to the inflamed segments of the intestine. Our group observed that CrF showed a conversion to beige tissue, a phenomenon known as "Browning", characterized by an elevated gene expression of thermogenin (UCP-1), the gene characteristic of browning1. A recent study also showed that when browning was induced in mice in a TNBS colitis model, mesenteric hypertrophy improved and inflammation in adipose tissue was reduced2. The aim of this study is to assess whether the administration of anti-TNF biologic treatment (infliximab) in patients with CD is related to the increase in adipose beige tissue in the CrF. Methods Immunohistochemistry staining of UCP-1 was conducted on CrF samples from CD patients receiving anti-TNF treatment (≥6 months) and anti-TNF-naïve patients. Additionally, we analysed the gene expression of beige adipose markers in CrF from CD patients treated with anti-TNF drugs, comparing them to those untreated. UCP-1 gene expression was also studied in adipose-stem cells isolated from CrF. Ongoing experiments involve treating adipose stem cells with infliximab (10ug/ml) for 24 hours to assess the potential conversion of white to beige adipose tissue. Results The study revealed a significant increase in UCP-1 staining in CrF samples among patients receiving anti-TNF treatment compared to anti-TNF-naïve CD patients (Fig 1.A). This trend was consistently observed in mesenteric CrF tissue. Beige markers TMEM26 and CPTB1 exhibited significant increases in anti-TNF-treated CrF, and other beige tissue markers showed a notable trend (Fig 1.B). Adipose stem cells displayed a significant increase in UCP-1 gene expression in anti-TNF-treated CrF compared to untreated patients (Fig 1.C). Exciting preliminary data suggest that infliximab treatment increases UCP-1 and the anti-inflammatory cytokine IL-4 gene expression in adipose-stem cells from active CD patients (Fig 1.D). This novel data implies a direct relationship between anti-TNF treatment and heightened browning in white adipose tissue of CD patients. Conclusion This study reveals a notable increase in UCP-1 gene expression in adipose tissue CrF of CD patients undergoing anti-TNF treatment. The findings suggest that anti-TNF therapy may trigger the transformation of white adipose tissue into the "beige" type, potentially mitigating inflammation. Browning CrF presents a promising therapeutic avenue for CD management, warranting further investigation. Ref: 1. D. Monfort-Ferré et al. J Crohn Colitis., 2022;16(10):1571–83, 2. Zuo L et al. J Crohn Colitis. 2023 21;17(8):1179-1192.

P067 Volumetric Assessment of Treatment Response in Newly Diagnosed Crohn Disease: A Pilot Study

Abstract Background Traditionally, mural thickness and disease length have been the radiological standards for assessing Crohn's Disease (CD) severity and treatment response. Our study aimed to evaluate and compare these linear measurements with volumetric ones in newly diagnosed pediatric CD, as well as to assess the concordance between manual and semi-automated volumetric methods. Methods In this single-center, prospective study, 20 children with newly diagnosed ileal CD treated with anti-TNF therapy from Dec 2018 to Oct 2021 (8 females; median age=14.5 years) underwent dedicated research MRI examinations at three timepoints – diagnosis (baseline) as well as 6 weeks and 6 months into therapy. For each exam and using T2-weighted Single Shot Fast Spin Echo (SSFSE) images, a single radiologist measured maximum bowel wall thickness (BWT, mm) and length of disease (cm). The inflamed ileum was manually segmented to measure tissue volume (ml) (Entrolytics; Motilent, London, UK). Semi-automated 3D volumetric measurements of the inflamed ileum (GI Seg tool) were created using the same platform. Estimated maximum BWT also was automatically calculated from manually-edited algorithmically generated masks. Mixed-effects models evaluated measurement changes over time. Intra-class correlation assessed absolute agreement between manual and automated volumetric assessments. Results BWT decreased over time with treatment (0.76 vs. 0.58 vs. 0.45 cm; p<0.0001), with a 24% decrease from baseline to 6 weeks and a 41% decrease from baseline to 6 months. Similarly, there was a significant decrease in length of disease over time (19.2 vs. 12.2 vs. 8.0 cm; p=0.002), with a 36% decrease from baseline to 6 weeks and a 58% decrease from baseline to 6 months. Manual volumetric measurements also showed a significant treatment response (19.8 vs. 11.6 vs. 5.1 ml; p<0.0001), with a 41% decrease from baseline to 6 weeks and a 74% decrease from baseline to 6 months. Using the semi-automated segmentation tool, the volume of inflamed bowel also decreased significantly over time (24.0 vs. 15.1 vs. 9.1 ml; p=0.0007), decreasing 37% between baseline and 6 weeks and 62% between baseline and 6 months. There was good agreement between manual and semi-automated volumetric bowel assessments (ICC=0.78 [95% CI: 0.57-0.88]). ICC between manual and code-estimated Max BWT was 0.60 [95% CI: 0.42, 0.72] with a strong positive correlation (r=0.839; p <0.001) between these two methods as shown in the Figure. Conclusion Volumetric assessments, along with automatic measurements of bowel wall thickness, show promise in accurately assessing treatment response in pediatric CD. These methods might provide more consistent and repeatable measurements, essential for long-term disease monitoring and management.

P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort

Abstract Background Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India. Methods Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse. Results Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%). Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A). Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse. Conclusion 60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.

P838 Determing factors that influence Vedolizumab Response in Inflammatory Bowel Diseases: A Prospective Study

Abstract Background In recent years, the development of biologic agents, including Vedolizumab, has offered new avenues for the treatment of IBD Understanding the factors that influence the response to Vedolizumab therapy is of paramount importance in optimizing patient care and treatment outcomes. However, for a drug like Vedolizumab, the exact concentration indicating the need for optimization and what influences it are still unknown. The aim of this research is to evaluate what parameter has influence on good response to Vedolizumab in patients with inflammatory bowel diseases. Methods 160 patients with Crohn's disease and ulcerative colitis were included in this prospective study, who were treated with Vedolizumab biological therapy from October 2018 to February 2023 at a tertiary center for inflammatory bowel diseases. All patients were followed for a minimum of 14 weeks or until therapy discontinuation. Biochemical parameters (CRP, fecal calprotectin, hemoglobin, ferritin), clinical parameters (MTWS, HBI) were monitored in all patients before and during treatment. Vedolizumab concentration was measured in half of the patients during treatment with this drug. All data were processed using the statistical program SPSS 23.0 (Chicago, IL). Results Of the 160 patients, there was almost an equal distribution between male and female (males, 160/86 (53.7%)), with an average age of 51.5 years (± 16.51 SD). After one year of therapy, a statistically significant reduction in inflammation parameters was observed (FCP- p=0.007, Z= -2.694; CRP- p=0.008, Z= -2.646), as well as a statistically significant clinical response to therapy by reducing the disease activity index (p < 0.000, Z= -4.818). Using logistic regression duration of disease nor disease localization are predictive parameters for response to therapy (p = 0.330, Exp B 1.190) In a group of 80 patients, Vedolizumab concentration was measured in a cross-sectional analysis. Our cohort of patients had a median Vedolizumab concentration of 20.73 µg/ml. Patients who achieved remission had statistically similar Vedolizumab concentrations compared to patients with active endoscopic disease (Vedolizumab concentration UC 25.6541 vs 28.8152; p = 0.614; CD 20.0232 vs 18.3346 µg/ml; p = 0.729). Patients on Vedolizumab who had previously received anti-TNF therapy had a lower mean drug concentration compared to bio-naive patients (16.05 ug/ml / 20.34 ug/ml). Conclusion Previous anti-TNF therapy may have an impact on drug concentration and response to therapy, but it is necessary to determine other parameters that can also independently influence drug concentration

DOP79 Promising efficacy of biologicals and small molecules for microscopic colitis: results from a large real-life multicenter cohort

Abstract Background Microscopic colitis (MC) is a chronic inflammatory condition of the colon, resulting in an impaired quality of life due to debilitating watery diarrhea. First-line therapy consists of budesonide, though a subset of patients is refractory or becomes budesonide- dependent. Evidence for the efficacy of biologicals or small molecules in MC is sparse and limited to small case series. Hence, we aimed to generate more real-life efficacy data. Methods This retrospective series was collected as part of the CONFER project by ECCO and supported by the European Microscopic Colitis Group (EMCG). Cases of MC patients treated with advanced therapies were included through a standardised collection form. Clinical response was defined as a 50% reduction in stool frequency (SF); clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Results Ninety-nine patients were identified (Table 1), of whom all but one were previously treated with budesonide. Reasons for budesonide discontinuation included primary non-response (PNR, 16.3%), refractory disease (34.7%), budesonide dependency (38.8%), or adverse events (AE, 10.2%). In total, 165 treatment cycles with advanced therapy (47 IFX, 40 ADA, 47 VDZ, 10 UST, 14 JAK inhibitors, 7 other) were reported. First-line advanced therapies included mainly anti-TNF (76.8%) and VDZ (20.2%) (Figure 1A). Patients were exposed to anti-TNF therapy for a median of 1.4 [0.5-3.1] years, with a significant drop in SF after induction (p<0.001), resulting in 50.0% clinical remission (Figure 1B). However, 63.0% ultimately discontinued anti-TNF therapy, mainly due to PNR (37.9%), loss-of-response (LOR, 36.2%) or AE (20.7%). VDZ induced 46.8% clinical remission, reflected in a significant drop in SF (p<0.001). Though, a 59.6% discontinuation rate was observed after a median 0.6 [0.3-1.3] years, mainly due to PNR (63.0%) and LOR (22.2%). Similarly, for UST a 40.0% clinical remission rate was accompanied by 60.0% therapy withdrawal, primarily due to PNR (83.3%). In contrast, JAK inhibition resulted in 78.6% clinical remission, with a substantial drop in SF (p=0.002) and 21.4% discontinuation rate after a median exposure of 0.6 [0.3-1.6] years. Conclusion Almost all advanced therapies are used in budesonide refractory or dependent MC, with anti-TNF agents the most often used first-line options. However, anti-TNF discontinuation is frequent due to lack/loss of efficacy. VDZ and UST could be alternatives, but also have a substantial discontinuation rate. In this retrospective series, the small number (n=14) of JAK inhibitor treated patients had the highest remission rate, suggesting further research on the role of JAK inhibitors in MC.

P169 Circulating eNAMPT predicts anti-TNF response in IBD patients: possible place in therapy of anti-eNAMPT antibody

Abstract Background extracellular Nicotinamide phosphoribosyltrasferase (eNAMPT) is a cytokine with paracrine and autocrine effects on different cell types. Importantly, eNAMPT levels are increased in patients suffering of Inflammatory Bowel Diseases (IBD). Biologic drugs have been found effective in many IBD patients; however, a large proportion of patients with severe disease fail to achieve remission due to lack of drug response, loss of response, drug intolerance, or severe side effects that require cessation of therapy. Therefore, there is a clinical need for predictive response biomarkers as well as for new therapeutic strategies. Methods First, we investigated the expression of NAMPT in biopsies, in stools and the secretion of eNAMPT in serum in four cohorts of IBD patients. Second, we investigated if circulating eNAMPT levels correlate with the clinical response to biologics (infliximab, adalimumab, ustekinumab, vedolizumab). Clinical response is defined as a reduction of >2 points in HBI (for CD) and in pMAYO (for UC) from baseline. Third, we have developed a monoclonal anti-eNAMPT antibody and we have evaluated its preclinical efficacy in acute and chronic preclinical models of IBD. Results We have determined the levels of circulating eNAMPT in three cohorts of patients that were not controlled by DMARDs and were treated with infliximab (IFX, cohort 1 and 3) or adalimumab (ADA, cohort 2). Notably, we confirmed a pronounced variability through the cohorts, identifying a group of patients with eNAMPT serum levels comparable with healthy adult populations and a group that showed elevated levels of eNAMPT. Performing a ROC curve analysis, a cutoff of 4.5 ng/ml can be extrapolated to discriminate these two populations. Noteworthy, 100% patients with levels of eNAMPT below 4.5 ng/ml were responsive to infliximab/adalimumab. In contrast, anti-TNF therapy failed either at 14 or 22 weeks in some patients with high circulating levels of eNAMPT, indicating that high systemic eNAMPT might be associated with an increased risk of resistance to anti-TNF therapy. Notably, we found also that eNAMPT levels in stools of IBD patients are elevated compared to healthy subjects. Then, we have developed and validated a candidate monoclonal antibody (called C269) which bind to eNAMPT, block is cytokine activity and reduces IBD symptoms, immune infiltrate and fibrosis in DSS and DNBS models. Conclusion Our data demonstrate that eNAMPT serum levels correlate with the clinical response to anti-TNF therapies suggesting that eNAMPT is not a simple by- stander of IBD, and that local and serum eNAMPT could be define as a biomarker to define the responsiveness to biologics. Notably, its neutralization might be a pharmacological strategy worth investigating.

P994 Single center assessment of intravenous ustekinumab maintenance in Crohn’s disease

Abstract Background Ustekinumab (UST) is usually employed in Crohn’s disease (CD) after anti-tumor necrosis factor (TNF) therapy failure or if anti-TNF therapy is contraindicated. Higher UST trough levels have been associated with better clinical/endoscopic outcomes, so dose escalation (reducing dosing intervals or reinduction) is widely used. Intravenous (iv) maintenance has been proposed, but it has been barely assessed. Methods Single center, retrospective case series. All patients with CD starting treatment with UST and receiving at least one dose were eligible. Subjects started on UST in other centers or those prescribed for any indication different than IBD were excluded. Dose escalation to iv maintenance was performed in case of lack or loss of response or persisting significant inflammation in laboratory tests, imaging or endoscopy. Following dose escalation, Harvey Bradshaw Index (HBI), fecal calprotectin and C reactive protein (CRP) were checked at each visit. UST trough levels were also assessed. Primary outcomes were clinical remission (HBI<5) and biochemical remission (fecal calprotectin <250 mg/kg). Adverse events, and treatment persistence were also assessed. Results A total of 131 patients treated between May 2017 and August 2023 were included. Sixty (45.8%) patients were escalated to iv UST maintenance after a median of 14.1 (IQR: 8-50.4) weeks of UST treatment. Baseline characteristics are shown in table 1. Patients were started on iv UST maintenance due to persistent inflammatory activity in imaging/endoscopic procedures in 21 (35%), clinical response without remission in 17 (28.3%), low trough concentrations in 16 (26.7%) and primary non-response in 6 (10%). Thirty-three (55%) were receiving sc UST every 4 weeks and 23 (38.3%) started iv maintenance directly after UST induction. At initiation of iv maintenance, patients presented a median HBI index of 4 (IQR: 2-7), a fecal calprotectin of 514 (IQR: 213-1078) mg/kg and UST trough levels of 4.8 (IQR: 3-7.3) μg/mL. Following iv maintenance, UST trough levels increased to 10.9 (IQR: 8-17.4). Clinical remission rates increased from baseline (48.3%) at weeks 8 (79.6%, p=0.001), 24 (72%, p=0.01) and 48 (74.4%, p=0.01). However, the 10-13% increase observed in the biochemical remission rates was not statistically significant (figure 1). Treatment persistence 2 years after starting UST iv maintenance was 72.2% (95% CI: 54.7-83.8%). Only 2 infectious adverse events were observed in the whole cohort (2/131, 1.6%), both in patients receiving sc maintenance. Conclusion UST iv maintenance in bio-experienced patients is safe and increases clinical remission rates, although it did not achieve a relevant improvement in biochemical remission rates.

P511 Short-term real-world effectiveness and safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: GRACE Study

Abstract Background The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn's disease (CD) pts who were underrepresented in CT is still limited. Methods GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of pts and their management and outcome 4 weeks after GMA treatment. Results A total of 95 evaluable pts were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of pts had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 pts (10.6%) with CD, all had B1, and 3 pts had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of pts had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of pts received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 pts reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed. Conclusion Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory pts with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of pts were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.

P323 Defining Normal Bowel Wall Thickness on Intestinal Ultrasound in an International Multicenter Cohort of Children with Inflammatory Bowel Disease in Sustained Deep Remission

Abstract Background Intestinal ultrasound (IUS) is a non-invasive, patient-centric tool for detecting and monitoring activity in patients with inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is the most important parameter for assessing IBD activity, however, normal values are extrapolated from adults. We aimed to define normal BWT in children with IBD who achieved sustained deep remission. Methods International, multicentre, retrospective, pediatric IUS database including IBD patients (< 18 years) without a prior history of surgery or complications who underwent IUS after achieving sustained deep remission: absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography or computed tomography enterography and steroid-free clinical remission from 2020-2023. Descriptive statistics summarized data as percentages for categorical variables and median [IQR] for continuous variables. Primary outcome was median BWT by segment: sigmoid colon (SC), descending colon (DC), transverse colon (TC), ascending colon (AC), and terminal ileum (TI), assessed using Kruskall Wallis. Secondary outcomes included univariate association of BWT and age, sex, disease duration, diagnosis (Crohn’s disease (CD) vs. ulcerative colitis (UC)/IBD-unspecified (IBD-U) and medication exposure. Results 80 patients (33 (41%) female; 51 (64%) CD:26 (33%)UC:3 (4%)IBD-U, median age 15.2 [14-16.6] years) with 400 bowel segments were included. Forty (50%) received anti-tumor necrosis factor therapy (anti-TNF), 18 (23%) ustekinumab (UST), 10 (12%) mesalamine(5-ASA), 6 (8%) vedolizumab (VDZ), 5 (6%) immunomodulator monotherapy (IM), and 1 (1%) upadacitinib (UPA) (Table 1). Median BWT was 1.3 [1.0-1.6]mm for SC, 1.3 [1.1-1.7]mm for DC, 1.3 [1.0-1.6] mm for TC, 1.3 [1.0-1.6]mm for AC, and 1.3 [1.1-1.5]mm for TI (Figure 1). There was no difference in BWT between segments (p=0.7952), age (p=0.1952) or sex (p=0.781). BWT was negatively associated with disease duration (p<0.05). UC patients had a 0.16 mm thinner BWT than CD (p<0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p<0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p<0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p>0.05). Conclusion Normal BWT for children with IBD in deep remission is less than adults, and unaffected by age, sex and bowel segment. BWT may be affected by disease duration, phenotype and medication exposure. These findings are crucial to the standardized assessment of transmural healing in children with IBD.

N31 HLA-DQA1*05 detection in saliva, an effective alternative in the monitoring and control of patients with Inflammatory Bowel Disease

Abstract Background The development of Inflammatory Bowel Disease (IBD) appears to be related to genetic susceptibility and an excessive immune response of the intestinal mucosa. Tumour necrosis factor (anti-TNF) therapies are the most widely used biologic drugs to treat immune-mediated diseases, but repeated administration may induce the formation of anti-drug antibodies. The ability to identify patients at increased risk of developing anti-TNFα antibodies would facilitate the selection of therapy and the use of preventive strategies. It has been shown that approximately 40% of the European population carries the HLA-DQA1*05 allele, and that its presence could have an important impact on treatment as it has been associated with: - Increased risk of immunogenicity of anti-TNFα therapy, regardless of concomitant treatment or anti-TNFα drug selected. - Decreased efficacy due to the formation of neutralising antibodies, leading to possible primary or secondary failures. - Occurrence of adverse events such as infusion reactions or hypersensitivity reactions. - Alterations in pharmacokinetics, so that drug clearance is accelerated regardless of whether the antibodies are neutralising. In our hospital we have the possibility to request the determination of the HLA-DQA1*05 allele through a detection kit in saliva. The main aim is to present a useful and effective tool for the detection of the HLA-DQA1*05 allele. Methods The methodology requires the inclusion of 30 newly diagnosed patients, patients naïve to biological treatment or patients on treatment with a first biological drug for no more than 24 months, by both the doctor and the nurse.The nurse will explain the previous preparation to the patient and will collect the sample using the saliva detection kit. Once the results have been received, the physician is notified. Results The detection of the HLA-DQA1*05 allele in our patients is 36.84%, a percentage similar to that detected in the European population through the detection of the HLA-DQA1*05 allele in blood. Conclusion - Having the ability to identify individuals at high risk of anti-TNF antibody formation and apply targeted combination therapy to these individuals is very valuable in clinical practice. - Saliva determination of the HLA-DQA1*05 allele is an efficient and cheaper alternative in hospitals where HLA-DQA1*05 detection in blood is not available in the laboratory. - The extraction and performance of the technique is simple, fast, obtaining the results within 5 days of submission, and convenient for both the patient and the healthcare professional.

P611 Relation between AntiTNF levels during the induction and clinical and radiological outcomes in perianal Crohn´s disease

Abstract Background Perianal Crohn's disease(PCD) significantly impacts quality of life with poor long-term prognosis. Anti-tumor necrosis factor(anti-TNF) therapy improves fistula closure rates. However, achieving permanent closure remains challenging. Our aim is to evaluate the relation between antiTNF(infliximab (IFX) and adalimumab(ADA) serum concentrations at induction(w2 and 6), and clinical and radiological outcomes at w24 and w52 Methods We conducted a single tertiary center, retrospective, cohort study including patients with an established diagnosis of PCD treated with antiTNF because of perianal activity. Variables related to their PCD(phenotype, location, fistulas type) were collected. Regarding treatment, we collected serum levels at week 2,6,24 and 52, concomitant treatment and setons presence. We defined clinical response as the absence of drainage on physical examination and clinical remission as the absence of external fistula openings. Radiological response was defined as the absence of T2 hypersignal, gadolinium enhancement, abscess and proctitis in pelvic MRI Results 65 patients were included, baseline characteristics are in Table1. None of the demographic characteristics collected were statistically significant related to clinical or radiological response although non smokers(p=0.01), ileal(p=0.02) and non-stricturing disease(p=0.01) had statistically significant higher drug levels. Taking into account the clinical response at w52, IFX mean levels at w2 were 25.8µg/mL(SD 4.1) in non responders and 30.9µg/mL(SD 14) in responders(p=0.39). At w6 they were 17.2µg/mL(SD 12.2) and 19.4µg/mL(SD 13.8) respectively(p=0.7). ADA mean levels at w2 were 13.3µg/mL(SD 7.7) in non responders and 14µg/mL(SD 6.3) in responders(p=0.87). At w6 they were 10.1µg/mL(SD 3.3) and 12µg/mL(SD 6.1) respectively(p= 0.59). For radiological response at w52 IFX mean levels at w2 were 27µg/mL(SD 15.3) in non responders and 32.7µg/mL(SD 14.5) in responders(p=0.45). At w6 the mean levels were 15.9µg/mL(SD 6.7) and 23.7µg/mL(SD 14.8) respectively(p=0.27). In ADA group the mean levels at w2 were 14.8µg/mL(SD 7.6) in responders and only one patient did not respond. At w6 ADA mean levels were 12.3µg/mL(SD 5.9) in non responders and 12.7µg/mL(SD 6.2) in responders(p=0.94). Early response at w24 was related with a long-term response at w52, 89.9% of the patients who responded at w52, had already responded at w24. Conclusion In our study we observed that almost 90% of the patients who had an early response also responded at w52, so trying to achieve an early response should be an aim in clinical practice. Despite the limited number of patients, our study shows a trend in the relationship between higher antiTNF levels and clinical and radiological response rates

DOP19 High dimensional profiling of IL-23-responsive cells revealed molecular signatures that predict response to anti-IL-23 therapy in patients with Crohn’s Disease

Abstract Background The interleukin (IL)-23 signaling plays a crucial role in the pathogenesis of Crohn’s disease (CD). IL-23 activates T-helper (Th) 17 cells, IL-17-secreting CD8 T (Tc)17 cells, gd T cells, nature killer (NK) T cells, and group 3 innate lymphoid cells (ILC3) to secrete proinflammatory cytokines including IL-17, IFN-g, and TNF-a. Risankizumab is the first selective IL-23 antagonist approved for moderate-severe CD. However, there is currently no biomarker to predict response to anti-IL-23 antibodies in IBD. Here, we characterized the cell type- and cytokine-specific pathways in IL-23-responsive cells that predict response to risankizumab in CD patients. Methods Adult patients with a history of ileal, colonic, or ileocolonic CD were included. Active CD in terminal ileum and/or colon were confirmed by colonoscopy and/or MRI. Blood samples were collected within 3 months before and 4, 8, 12, and 52 weeks after the initiation of risankizumab. Peripheral blood mononuclear cells (PBMC) were isolated and cryopreserved for batch analysis using mass cytometry (CyTOF). Pre-treatment PBMCs were stimulated ex vivo with IL-23, and stained for lineage markers to identify Th17, Tc17, gd T, NKT cells, and ILC3, as well as intracellular cytokines including IL-17, IFN-g, TNF-a, IL-22, IL-6, and GM-CSF, using a pre-optimized and validated antibody panel. The CyTOF data were analyzed using the viSNE tool in Cytobank and FlowJo. Patients’ responses were evaluated 12-40 weeks after the initiation of risankizumab based on clinical symptoms and endoscopic/radiographic assessment. Results Among IL-23-responsive cells, increased frequency of NKT cells was identified in the peripheral blood of non-responders before initiation of risankizumab (Figure 1A). In non-responders, Tc17 cells, gd T cells, and ILC3 demonstrated significant elevations in TNF-a, a key pathogenic mediator in CD. gd T cells from non-responders also showed increased IL-17F before treatment. In contrast, NKT cells from non-responders expressed significantly lower GM-CSF, which was previously shown to alleviate intestinal inflammation in patients and mouse models (Figure 1B). Ongoing study is investigating the cytokine production in IL-23-responsive cells after the initiation of risankizumab, as well as before and after starting ustekinumab, an anti-IL-12/IL-23 antibody. Conclusion High dimensional profiling of pre-treatment PBMCs revealed molecular signatures, e.g., elevated TNF-a in multiple IL-23-responsive cells, which are associated with resistance to risankizumab in CD patients. Those findings may help identify response biomarkers for IL-23 antagonists and provide a rationale for using anti-IL-23/anti-TNF combination therapy in some patients with refractory CD.

P383 Chronic Recurrent Multifocal Osteomyelitis associated with Paediatric Inflammatory Bowel disease: A Multi-Center Retrospective Study from the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder. CRMO was linked with inflammatory bowel disease (IBD), either as an extra intestinal manifestation or as a paradoxical effect of anti-TNFa therapy. Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD Methods Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in nineteen centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings and outcomes of each disease Results Forty five patients (21 [47%] females) with a diagnosis of CRMO and IBD (32 [71%] with Crohn’s disease) were included. Median age at the time of dual diagnosis was was 10.2 (IQR 12-13.5) years. Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 8 (53%) and 2 (13%) exhibiting mild and moderate-severe IBD activity, respectively. In 20 children (44%) IBD preceded CRMO diagnosis by >3 months with a median time of 238 (85-344) weeks. At the time of dual diagnosis, 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate-severe disease activity; however, CRP and ESR were elevated (1.5 [0.4-3.4] mg/dL and 35 [21-55] mm/h, respectively) while median fecal calprotectin was 567 (68-1800) mcg/gr, including 4 patients <100 mcg/gr. 17 patients (85%) were on anti-TNFa medication at the time CRMO developed. In 10 (22%) patients CRMO preceded the diagnosis of IBD (>3 months before IBD evolution) with a median time 46 (25-248) weeks. At time of IBD presentation, CRMO was in remission in 5 patients (50%). 4 patients were diagnosed with IBD, despite the lack of any abnormal gastro-intestinal symptoms. In patients in which CRMO was diagnosed after or during IBD diagnosis, different therapeutic regimens were used, including anti-TNFa agents, methotrexate, ustekinumab, NSAID’s and corticosteroids. Two patients also received bisphosphonates. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission, defined as lack of bone pain, was achieved in 22.2 (15-51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and bone deformity Conclusion In the largest cohort to date, CRMO presentation was not necessarily related to clinically active intestinal inflammation and could present before, during or after IBD diagnosis. CRMO remission was achieved in all patients; Nevertheless, a small number of patients developed significant bone complications

DOP10 Risankizumab Versus Ustekinumab for the Achievement of Endoscopic Outcomes in Patients With Moderate-to-Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE Trial

Abstract Background The SEQUENCE study compared the efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate-to-severe Crohn's disease (CD) who previously failed ≥1 anti-tumour necrosis factor (TNF)a therapies. The second primary endpoint of SEQUENCE, week (wk) 48 endoscopic remission, demonstrated superiority of RZB versus (vs) UST.1 Here, additional endoscopic and clinical/endoscopic composite outcomes are reported. Methods SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study. Pts had a baseline (BL) CD Activity Index (CDAI) of 220-450, average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2, and Simple Endoscopic Score for CD (SES-CD) ≥6 (≥4 for isolated ileal disease). Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, wk4 and wk8, then 360mg subcutaneous [SC] maintenance doses every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance treatment starting at wk8) up to wk48. Randomisation was stratified by BL steroid use and number of failed anti-TNFa therapies. A mandatory steroid taper began at wk2. Here, we assessed at wks 24 and 48 endoscopic remission (SES-CD ≤4 and at least a 2-point reduction versus BL and no subscore >1 in any individual variable, as scored by a central reader), mucosal healing (SES-CD ulcerated surface subscore of 0 in pts with SES-CD ulcerated surface subscore ≥1 at BL, as scored by a central reader), and deep remission (endoscopic remission + clinical remission [CDAI<150]); all were prespecified, non-ranked endpoints, except for wk48 endoscopic remission (second primary endpoint). Treatment differences were adjusted for the randomisation stratification factors. Missing data were handled using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. P values were reported as nominal, except for wk48 endoscopic remission. Results With RZB vs UST, a greater proportion of pts achieved endoscopic remission (wk24: 29.4% vs 17.4%, P= 0.001; wk48: 31.8% vs 16.2%, P<0.0001), mucosal healing (wk24: 25.1% vs 14.4%, P<0.01; wk48: 30.2% vs 12.1%, P<0.0001), and the composite endpoint of deep remission (wk24: 22.0% vs 10.2%, P< 0.001; wk48: 22.7% vs 10.9%, P<0.001) at wk24 and wk48 (Figure). The safety profiles of RZB and UST were consistent with published results.1 Conclusion Exploration of endoscopic outcomes demonstrated that pts with moderate-to-severe CD and prior anti-TNFa failure showed greater achievement of endoscopic remission, mucosal healing, and deep remission with RZB compared to UST. 1doi.org/10.1002/ueg2.12474

P846 Impact of 5-ASA discontinuation in children with ulcerative colitis under biological therapy

Abstract Background Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα. Methods Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded. Results Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p < 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003). Conclusion Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.

P510 Relapse rate following withdrawal of vedolizumab and ustekinumab in patients with inflammatory bowel disease. The VEDUST-EXIT study

Abstract Background Approximately half of patients with IBD in clinical remission (CR) flare within 12 months of withdrawing anti-TNF therapy. However, the outcomes of vedolizumab (VDZ) or ustekinumab (UST) cessation in terms of CR in routine practice are unknown. There is a need for more data to establish the relapse rates following treatment cessation. Methods This was a retrospective observational multicenter study. We included adult IBD patients who had withdrawn from either VDZ or UST after achieving CR and had available follow-up data for one year following treatment discontinuation or until relapse occurred. The control arm comprised patients discontinuing anti-TNFs after achieving CR. The primary objectives of this study are to assess the clinical relapse rates after discontinuing VDZ or UST and to identify potential predictors of sustained remission and relapse after therapy discontinuation. Results A total of 133 patients were included (48.1% Crohn’s disease and 51.9% ulcerative colitis). Sixty out of the 133 (45%) patients discontinued anti-TNF, 54 (40%) VDZ and 19 (15%) UST. All patients were in CR prior to drug discontinuation. The most common cause for drug discontinuations was patients’ preferences (80%) followed by cost and administrative issues. Duration of remission before drug discontinuation was 11 (IQR 7.5-10), 8.5 (6-12.2), and 12 (8-27) months, for anti-TNF, VDZ, and UST, respectively. The median follow-up duration was 14 months (5.5-20), with an overall relapse rate of 78.9% (105/133). Relapse rates in each cohort were 71.6%, 83.3%, and 89.4%, respectively, p=0.5. The median time to relapse was 10 months (3-9), 9 (6-16.5), and 8 (5-16.5), respectively. There was no significant difference in the relapse rates between the different drugs (anti-TNF vs VDZ, anti-TNF vs UST, and VDZ vs UST, (hazard ratio, HR 1.2, confidence interval, CI 95% 0.2-1.8; P = 0.35), HR 1.2, CI 95% 0.9-1.6; p=0.13, HR 1.2, CI 95% 0.6-2.1; P=0.5, respectively). Predictors of relapse after drug withdrawal were a short treatment period (HR 0.98, CI 95% 0.96-0.99; P = 0.04), shorter remission period (HR 0.9, CI 95% 0.95-0.99, P =0.03), multiple prior biologics (HR 1.2, CI 95% 1.04-1.44, P= 0.013), perianal disease (HR 5.5, CI 95% 1.6-1.8, P=0,006) and lower hemoglobin level (HR 1.95, CI 95% 1.1-3.1, P= 0.008). The following factors were not associated with an increased risk of relapse: IBD type, disease phenotype, extraintestinal manifestations, active smoking status, prior IBD-related surgery, elevated CRP or calprotectin, and endoscopic or radiologic signs of active disease. Conclusion In IBD patients that discontinue biologics after achieving clinical remission, relapse rates following withdrawal of VDZ and UST are comparable with those of anti-TNF.