Vedolizumab Group Research Articles

P0641 Efficacy of Vedolizumab and Ustekinumab Following Cyclosporine Induction in Acute Severe Ulcerative Colitis: A Retrospective Cohort Study

Abstract Background In corticosteroid-resistant acute severe ulcerative colitis (ASUC), second-line treatment involves infliximab or cyclosporine (CYCLO). With increasing antiTNFα exposed patients, CYCLO is often chosen to prevent emergency colectomy but is limited to the induction phase due to tolerability, serving as a bridge until effective maintenance therapy. In this setting, limited data on vedolizumab (VDZ) and ustekinumab (UST) as maintenance make the choice of an optimal bridge strategy challenging. This study aimed to compare the efficacy of VDZ and UST after CYCLO induction in corticosteroid-resistant ASUC. Methods This single-center retrospective cohort included all patients hospitalized for ASUC, responding to CYCLO induction, and starting VDZ or UST maintenance. ASUC was defined by modified Truelove and Witts criteria, with response to CYCLO defined by a Lichtiger score reduction to <10 points for 2 consecutive days, with a minimum 3-point decrease by day 7. The primary outcome was colectomy-free survival; secondary outcomes were treatment persistence and safety. Results From 2014-2024, 72 ASUC patients received CYCLO. Fourteen were excluded (non-response, tofacitinib [n=6], infliximab [n=3], and/or emergency colectomy [n=11]), leaving 58 CYCLO-responsive ASUC patients (median age 39, IQR 30-58, 60% female), with 46 on VDZ (79%) and 12 on UST (21%). ASUC was related to ulcerative colitis in 81% (68% pancolitis) and Crohn’s in 19%. Disease duration was 7 years (IQR 2-15), with 91% prior biologic exposure, primarily antiTNF. Presentation included Lichtiger score 10 (IQR 10-12), CRP 40 mg/L (22-79), albumin 29 g/L (27-30), fecal calprotectin 874 µg/g (450-1800), UCEIS 7 (5-8), and Mayo endoscopic score 3 (3-3). Colectomy-free survival was 75% at M12 and 69% at M24 with VDZ and 57% at M12 and M24 with UST (p=0.38, figure 1). Treatment persistence was 48% at M12 and 37% at M24 with VDZ, and 42% at M12 and M24 with UST (p=0.51, figure 2). After adjusting for maintenance therapy, disease type, and severity, colectomy risk factors included albumin <27 g/L (HR=3.4; 95%CI:1.2-9.8) and prior tofacitinib exposure (HR=4.3; 95%CI:1.2-15.8). Over a median 37-month follow-up (95%CI:35-40), 34% of patients experienced adverse events, with 19% severe (mainly CYCLO-related), including 2 deep vein thromboses in the VDZ group and 1 infection in the UST group. No deaths occurred. Conclusion In this large cohort of biologic-exposed, corticosteroid-resistant ASUC patients, a CYCLO bridge strategy with VDZ or UST avoided colectomy in two-thirds of patients, with almost 50% treatment persistence at 12 months. There was no significant difference in efficacy, persistence, or safety between strategies.

P1036 The PODIUM Study: A three-arm comparison of target therapies after anti-TNFα in ulcerative colitis – an interim analysis

Abstract Background Anti-tumor necrosis factor(TNF)α are the first target therapies approved to treat ulcerative colitis(UC). Drugs with different mechanisms of action(MoA) have then entered the market, but data on the optimal management of UC after failure of 1-line anti-TNFα are lacking. Methods The PODIUM study is a retrospective, observational study comparing the real-life effectiveness and safety of 2-line vedolizumab(VDZ), ustekinumab (UST) and JAK inhibitors(JAKi). Consecutive UC patients(pts) failure to 1+ anti-TNFα and never exposed to other MoA were enrolled from 13 European centres. Sociodemographic data, data on clinical activity and adverse events of interest(AEIs) were collected, from the initiation of 2-line therapy until 1 year of observation/drug discontinuation/last follow-up. The primary outcome was steroid-free clinical remission(SFCR); inverse probability of treatment weighting(IPTW) was applied to all outcomes. This interim analysis includes data collected up to August 2024; data collection is still ongoing. Results Data on 352 patients (187VDZ, 76UST, 89JAKi) were included. Baseline characteristics are presented in Table1. After IPTW, the cumulative probability of achieving SFCR during the first year was 52%, 68% and 71% for VDZ, UST and JAKi, respectively; both UST and JAKi were superior to VDZ at Log-rank test(p<0.05), with no differences between the two (Figure1). Stool frequency scores were significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.5 and 0.5 vs 1.2, p<0.05 for both); rectal bleeding scores were nearly significantly lower at 12 months in the UST- and JAKi-groups, compared to the VDZ-group(0.2 and 0.2 vs 0.6, p<0.05 for both). Recorded AEIs were 10(5.3% of VDZ pts, 4 infections) in the VDZ group, 7(9.2% of UST pts, 1 infection) in the UST group, 17(19.1% of JAKi pts, 10 infections including 1 Zoster reactivation) in the JAKi group. Conclusion This preliminary analysis suggests that both UST and JAKi might have superior effectiveness, compared to VDZ, as second-line agents in patients with UC, after anti-TNF-α. A significantly higher rate of AEIs was observed in the TOF group. Confirmatory analysis with a larger sample size will be performed.

P0667 Therapeutic Optimization of Biologic Therapy in Ulcerative Colitis: A Retrospective Analysis of Endoscopic and Biomarker Outcomes

Abstract Background Biologic therapies have transformed the management of ulcerative colitis (UC), offering effective options for achieving remission. However, some patients require therapy optimization, guided by clinical and endoscopic assessments, to enhance outcomes. Despite their routine use, real-world comparisons of optimization strategies for different biologics remain limited. This study evaluates the impact of endoscopy-guided optimization on remission rates and safety profiles in a UC cohort. Methods This retrospective study included consecutive patients at the Humanitas outpatient clinic from 2021 to 2023 who underwent endoscopy-guided therapy optimization. All patients had minimal clinical activity (pMayo score <2) and underwent colonoscopy to assess biologic therapy response. Statistical analyses included the Student’s t-test or Mann-Whitney U test for continuous variables, and chi-square or Fisher’s exact test for categorical variables. Propensity score matching (PSM) was used to balance baseline characteristics, including bio-experienced status. Results A cohort of 176 UC patients was included. Among them, therapy optimization with anti-TNFs was used in 41.2% for infliximab, 19.9% for adalimumab, and 4.6% for golimumab, while 14.4% received ustekinumab and 17.1% vedolizumab. Multivariate logistic regression analysis identified key predictors for outcomes: patients who were biologic-experienced at baseline had significantly reduced odds of achieving endoscopic remission at 12 months following optimization (odds ratio [OR] = 0.223, 95% CI: 0.070–0.711, p = 0.011). Other variables, including age at diagnosis, disease extent, and specific biologic therapy (anti-TNF vs. ustekinumab vs. vedolizumab), were not statistically significant predictors of remission. In the PSM-adjusted dataset, endoscopic remission rates were 61.5% for anti-TNFs, 33.3% for ustekinumab, and 60.0% for vedolizumab (p = 0.666, chi-square test). Biochemical remission was also highest in the anti-TNF group (61.8%), significantly greater than in ustekinumab (26.7%) and vedolizumab (53.3%) (p = 0.042, chi-square test). Adverse events were least frequent in the ustekinumab and vedolizumab groups, with only 3.5% reported for anti-TNFs (p = 0.293, Fisher’s exact test). Adverse events remained low across all groups, with a tendency toward fewer events in the ustekinumab and vedolizumab groups compared to anti-TNFs, though these differences were not statistically significant (p = 0.324, Fisher’s exact test). Conclusion The optimization of Anti-TNFs showed superior endoscopic healing and biomarker remission rates compared to ustekinumab and vedolizumab, with all groups exhibiting low adverse event rates.

P0565 Spatial Metabolic Profiles in Ulcerative colitis patients determine response to therapy

Abstract Background Ulcerative Colitis (UC) is an heterogenous debilitating disease without a cure. The step-up therapy approach aims at controlling and alleviating intestinal inflammation by achieving and maintaining clinical and endoscopic remission. However, the rate of primary non-response or loss of response to therapies is still high. Predictive markers that accurately guide decisions about the best therapeutic choice are an unmet need. This study aims to determine the intestinal metabolic profiles of UC patients and explore differences in response groups of given treatments, thus helping a better patient stratification. Methods Mucosal biopsies collected from active UC patients (N=26) at week 0 and 14 after treatment (vedolizumab, tofacitinib and filgotinib) were sectioned at 10 µm thickness. Patients were classified as non-responders (NR), responders (R) and super responders (SR) based on both endoscopic and partial Mayo scores. Sections were processed by matrix-assisted laser desorption/ionization (MALDI) coupled with Orbitrap Exploris™ 120 Mass Spectrometer. Raw spectral data was processed with MSConverter and MSIpixel for metabolite quantification and annotation. Comprehensive statistical analyses including quantitative metabolite distributions, Moran’s I spatial correlations and pathway enrichment analysis were performed via an in-house developed computational pipeline. Results Spatial metabolomic analysis revealed different metabolite patterns between R and NR across all drugs. Notably, all non-responders exhibited a dysregulated lipid metabolism. In the Vedolizumab group, a fragmented pattern distribution of metabolites was found in NR characterized by an increase of canavalmine, N1-acetylspermidine and heptanenitrile at week 0, whereas SR showed a significant tissue reorganization environment, with increased number of metabolites such as LysoPA, LysoPE and 5alpha-Cholesta-7,24dien-3beta-ol, involved in anti-inflammatory pathways, as well as glutathione and purine metabolism. Additionally, SR showed histamine- and IgE-related pathways supporting cellular regeneration. Conclusion Overall, these data depicted the alteration of mucosal lipid metabolism as a hallmark of non-response to therapies, and evidenced that the effectiveness of a specific treatment in UC is impacted by the initial mucosal metabolic state conditioned by diet and medications. The validation of these results in a larger sample size will aid the prediction of therapy response. References ImmUniverse project: this project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 853995. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The content provided in this abstract reflects only the author's view and neither the IMI JU nor the European Commission are responsible for any use that may be made of the information it contains.

P1111 Infliximab is not Superior to Vedolizumab for the Treatment of Moderately to Severely Active Ulcerative Colotis with PR3-ANCA Positive : A Retrospective Multicentre Real-World Study

Abstract Background Current literature presents conflicting findings about the efficacy of Infliximab (IFX) versus vedolizumab (VDZ) in patients with moderately to severely active ulcerative colitis (UC). Patients with UC who are positive for anti-neutrophil cytoplasmic antibodies(ANCA) are known to respond poorly to IFX1-3 and VDZ4. We aimed to evaluate the comparative efficacy and safety of IFX versus VDZ in moderately to severely active UC patients with Proteinase 3-ANCA(PR3-ANCA) positive. Methods This retrospective multicentre real-world study was conducted in three centers in Hubei, China. Patients with moderate to severe active ulcerative colitis (UC) who are positive for PR3-ANCA were allocated to either the Vedolizumab (VDZ) group (n=19) or the Infliximab (IFX) group (n=26) depending on the biologics they received. The endpoints assessed at week 22 included clinical remission(primary endpoint), clinical response, endoscopic response, and endoscopic remission. Inverse probability of treatment weighting (IPTW) was employed to ensure the reliability and robustness of the clinical outcomes. Results In the original cohort, IFX was not superior to VDZ in terms of clinical remission (23.08% vs. 42.11%, P=0.173), clinical response (65.38% vs. 63.16%, P=0.878), endoscopic response (57.69% vs. 63.16%, P=0.712), and endoscopic remission (11.54% vs. 26.32%, P=0.253). Additionally, similar outcomes were observed in the IPTW cohort: for clinical remission (23.26% vs. 35.89%, P=0.384), clinical response (68.68% vs. 60.29%, P=0.583), endoscopic response (58.48% vs. 60.29%, P=0.912), and endoscopic remission (14.18% vs. 22.75%, P=0.494) when comparing IFX to VDZ. Conclusion IFX is not superior efficacy compared to VDZ in moderately to severely active UC patients with PR3-ANCA positive.

Vedolizumab to prevent postoperative recurrence of Crohn's disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial.

Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease. REPREVIO was a double-blind, randomised, placebo-controlled trial conducted at 13 academic or teaching hospitals in France, Italy, the Netherlands, and Spain. Eligible participants were adult patients aged 18 years or older with Crohn's disease who underwent ileocolonic resection and had one or more risk factors for recurrence. Patients were randomly assigned within 4 weeks of surgery (1:1 ratio) to receive intravenous vedolizumab (300 mg) or placebo at weeks 0, 8, 16, and 24. Randomisation was performed centrally with a computer-generated validated variable block model and patients were stratified according to disease behaviour (fibrostenotic vs inflammatory or perforating). Ileocolonoscopy was performed at week 26 and videorecorded. Endoscopic recurrence was centrally assessed with the modified Rutgeerts score, a categorial score ranging from i0 to i4. The primary endpoint was the distribution of modified Rutgeerts scores between treatment groups at week 26, analysed by non-parametric methods. The first-ranked secondary endpoint was the proportion of patients with severe endoscopic recurrence of Crohn's disease at week 26 (modified Rutgeerts score ≥i2b). Primary and safety analyses included all patients who underwent randomisation and received at least one dose of study drug. The trial is registered with the EU Clinical Trial Register (EudraCT; 2015-000555-24). Between May 16, 2017, and April 8, 2022, 84 patients were randomly assigned to treatment, of whom four did not receive study treatment, leaving 43 patients in the vedolizumab group and 37 in the placebo group. At week 26, the probability of a lower modified Rutgeerts score with vedolizumab versus placebo was 77·8% (95% CI 66·4 to 86·3; p<0·0001). Severe endoscopic recurrence was observed in ten (23·3%) of 43 patients in the vedolizumab group versus 23 (62·2%) of 37 patients in the placebo group (difference -38·9% [95% CI -56·0 to -17·3]; p=0·0004). Serious adverse events occurred in three (7·0%) of 43 patients who received vedolizumab (bilateral tubo-ovarian abscesses, thrombosed haemorrhoids, and pancreatic adenocarcinoma) and in two (5·4%) of 37 patients who received placebo (intestinal perforation related to Crohn's disease and severe abdominal pain). Vedolizumab treatment within 4 weeks of ileocolonic resection was more likely to prevent endoscopic Crohn's disease recurrence than placebo, making this an attractive option for postoperative management in patients with risk factors for recurrence. Larger studies with longer follow-up would be desirable. Takeda Nederland.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort

IntroductionBiological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. MethodsMulticenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included.Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients’ colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). ResultsA total of 1090 patients were included. After induction, at approximately 12–14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response.At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab – 9 patients (37.5%) – compared to the other biological treatments analyzed.With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments.As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. ConclusionsBiological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy.In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Real-World Treatment Outcomes Associated With Early Versus Delayed Vedolizumab Initiation in Patients With Ulcerative Colitis.

Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy. RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate). At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28-4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72-1.90) or at 12 months (OR, 0.872; 95% CI, 0.55-1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims. Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.

Comparison of the Effectiveness of Vedolizumab and Ustekinumab in Patients with Ulcerative Colitis: A Real-World Retrospective Study.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine. Data on the comparative effectiveness of biological therapies such as vedolizumab (VDZ) and ustekinumab (UST) remain limited. This retrospective study compared the effectiveness and safety of VDZ and UST in UC patients. Between November 2018 and November 2023, 106 patients were included: 64 received VDZ and 42 received UST. Bio-failure was significantly higher (p = 0.005) in the UST group versus the VDZ group. The remission rates at 6, 22, and 54 weeks in VDZ group were 51.6%, 61.3%, and 66.7%. The remission rates at 8, 24, and 56 weeks in the UST group were 66.7%, 65.0%, and 66.7%, respectively. Both treatments were comparable in inducing and maintaining clinical remission over 54-56 weeks, with no significant differences observed in the Lichtiger clinical activity index. Subgroup analyses highlighted the potential short-term effectiveness of UST among cases of bio-failure and a white blood cell level ≥ 9000/µL. Safety profiles were generally favorable, with no significant adverse events. Usutekinumab demonstrated effectiveness as a salvage therapy in patients who failed VDZ. Despite the increased disease severity in the UST group compared to the VDZ group, both groups demonstrated similar remission rates, suggesting UST shows significant efficacy even in moderate to severe UC.

Serological responses to vaccination in children exposed in utero to ustekinumab or vedolizumab: cross-sectional analysis of a prospective multicentre cohort

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.What is known:• Treatment with anti-TNF inhibitors during pregnancy does not appear to affect serologic response to vaccination in exposed children.• Evidence on the efficacy of vaccination in children exposed to ustekinumab or vedolizumab in utero is almost lacking.What is new:• Our findings suggest that in utero exposure to ustekinumab or vedolizumab does not significantly affect the serological responses to common childhood non-live (tetanus, Haemophilus influenzae B, diphtheria) and live vaccines (measles, mumps, rubella).• No major adverse effects on overall immunological health were observed in children exposed in utero to ustekinumab or vedolizumab.

Efficacy of Ustekinumab and Vedolizumab Among Postoperative Crohn's Disease Patients as Postoperative Prophylaxis and Rescue Therapy: Real-world Data.

Almost half of patients with Crohn's disease (CD) require bowel surgeries in their lifetime. Due to the high risk of postoperative disease recurrence and high rate of previous antitumor necrosis factor (anti-TNF) failure, often alternative therapy options such as ustekinumab (UST) and vedolizumab (VDZ) are used. We aimed to evaluate the efficacy of UST and VDZ among postoperative CD patients as postoperative prophylaxis and rescue therapy. Consented CD patients who underwent initial ileocecal resection and were treated with UST and VDZ were included in this study. Demographics, clinical characteristics, health care utilization, endoscopy scores, and surgery outcomes were collected. Postoperative early CD recurrence was defined as a Rutgeerts endoscopic score ≥i2 within the first 2 years. The rescue therapy group was defined as patients who received either UST or VDZ after having Rutgeerts endoscopic score ≥i2 postoperatively. During 2009 to 2019, 98 CD patients were treated with UST or VDZ postoperatively. Postoperative early recurrence rates were 5% (n = 1 out of 20) and 6% (1 out of 15) for the UST and VDZ groups, respectively. Two patients from the UST group and 1 patient from the VDZ group required bowel surgery during follow-up with median drug exposure of 51 (95% confidence interval [CI], 29-61) and 30 (95% CI, 14-63) months, respectively; 55% and 69% of patients had at least 1 point of improvement on postoperative endoscopic Rutgeerts score, respectively, for UST and VDZ. Only 3 out of 40 and 1 out of 23 patients required bowel surgery during follow-up while receiving UST and VDZ as rescue therapy. Both UST and VDZ were effective as postoperative therapies either as prophylaxis or rescue therapy.

Randomized clinical trial of infliximab versus vedolizumab for immune checkpoint inhibitor related colitis.

2661 Background: Immune-mediated diarrhea and colitis (IMDC) is an inflammatory consequence of immunotherapy that frequently necessitates discontinuation of immunotherapy. Current management strategies are adopted from inflammatory bowel disease practice and rely on selective immunosuppressive therapy (SIT) with infliximab or vedolizumab as first-line in more severe cases. While this practice is widely accepted, evidence supporting SIT use is limited to retrospective studies. Here we present the preliminary findings of 22 patients from the first clinical trial comparing the efficacy and safety of infliximab and vedolizumab in treating IMDC. Methods: We conducted a randomized controlled trial of infliximab and vedolizumab in the treatment of IMDC. To be included, patients must have received immunotherapy and developed immune-mediated diarrhea or colitis at CTCAE grade ≥2. Infusions were given around weeks 0, 2, and 6, and disease activity and incidence of adverse events were recorded over 12 weeks of follow-up. Remission was defined as symptom improvement to CTCAE grade ≤1 by week 2. Fecal transplantation or ustekinumab would be considered for patients who are refractory to two SIT doses. Results: 22 patients have been enrolled thus far, three of whom were removed from the study and one who withdrew consent at 2 months. Ten patients were randomized to the infliximab arm and nine to the vedolizumab arm. At two weeks, clinical remission rates are similarly high across infliximab (90%) and vedolizumab (88.9%) groups, with the one patient in the vedolizumab group having symptom improvement but failing to meet criteria for clinical remission and one in the infliximab group with treatment failure. Symptom improvement was typically seen in a median of 3 days (IQR: 1.5-5.5) across both groups. Eight patients (80%) in the infliximab group and seven patients (77.8%) in the vedolizumab group had steroid-free remission at one month. Four patients (40%) from the infliximab group and three (33.3%) from the vedolizumab group had symptom recurrence in a median of 43 days across both groups (IQR: 39-93). Three patients from either group were able to resume immunotherapy. In terms of safety, both groups had a similar rate of mild adverse events (AEs), most of which were deemed unrelated to SIT use. Conclusions: This is the first randomized controlled trial to evaluate the safety and efficacy of infliximab and vedolizumab in the management of IMDC. Our results suggest that both agents are equally effective at controlling symptoms within two weeks of the first infusion, with a small number of patients receiving either having recurrent disease. The two drugs have a comparable safety profile with primarily mild AEs occurring. Our preliminary findings suggest that both drugs can be used effectively in first-line treatment of IMDC, but further data is necessary to ascertain long-term outcomes. Clinical trial information: NCT04407247 .

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort

IntroductionBiological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. MethodsMulticenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included.Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients’ colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). ResultsA total of 1090 patients were included. After induction, at approximately 12–14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response.At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab – 9 patients (37.5%) – compared to the other biological treatments analyzed.With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments.As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. ConclusionsBiological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy.In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Effectiveness and safety of vedolizumab and infliximab in biologic-naïve patients with moderate-to-severe ulcerative colitis: A multicenter, retrospective cohort study.

We conducted this multicenter, retrospective cohort study aiming to evaluate the effectiveness and safety of vedolizumab (VDZ) and infliximab (IFX) in biologic-naïve patients with moderate-to-severe ulcerative colitis (UC). Biologic-naïve patients with moderate-to-severe UC who were treated with IFX or VDZ for at least 14 weeks at three tertiary hospitals in southwest China between January 2021 and January 2023 were retrospectively included. Efficacy of the biologics was evaluated based on the steroid-free clinical remission rate, clinical remission rate, and mucosal healing rate at Weeks 14 and 52. Adverse events related to biologic use were recorded. Altogether 122 biologic-naïve patients with moderate-to-severe UC were included. No marked differences in the steroid-free clinical remission rate and clinical remission rate were observed between the two groups at Week 14 or Week 52 (P > 0.05). The VDZ group exhibited a higher mucosal healing rate at Week 14 compared to the IFX group (33.3% vs 16.9%, P = 0.036), while that at Week 52 did not differ between the two groups (65.6% vs 47.1%, P = 0.098). There was no statistically significant difference in the rate of adverse events between the two groups (P = 0.071). VDZ and IFX showed comparable clinical efficacy and safety profiles and can be used as viable first-line therapeutic options for biologic-naïve patients with moderate-to-severe UC.

INFLIXIMAB AND VEDOLIZUMAB HAVE SIMILAR CLINICAL AND SAFETY OUTCOMES AMONG BIOLOGIC-NAÏVE PATIENTS WITH MILD TO MODERATE PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Infliximab (IFX) is the only FDA-approved intravenous therapy for the treatment of pediatric inflammatory bowel disease (IBD). The gut-selective anti-integrin vedolizumab (VDZ) has been increasingly used as second-line therapy. However, the comparative effectiveness of IFX vs. VDZ to treat biologic-naïve children with IBD is currently unknown. AIMS 1. Compare the real-world effectiveness of IFX vs. VDZ in bio-naïve pediatric patients with IBD at 12 months. 2. Study the safety of IFX and VDZ in the pediatric population. METHODS A single-center retrospective cohort study was conducted at an academic children’s hospital between February 2015 and August 2023. We included bio-naive mild-moderate IBD patients, &amp;lt;23 years old, who started IFX or VDZ as their first advanced therapy. Patients with a confirmed diagnosis of IBD based on Porto criteria with baseline and at least 6-month follow-up data were included. Exclusion criteria were designed to limit the study population to patients who would typically be eligible for vedolizumab treatment according to the current standard of care, including: prior biologic use; steroid-refractory acute-severe colitis; stricturing or penetrating Crohn’s disease (CD); or perianal disease; and extraintestinal manifestations. The primary outcome was steroid-free clinical remission (SFCR) at 12 months, defined by the PUCAI &amp;lt;10 or ShPCDAI &amp;lt;10 and off corticosteroids. Biochemical remission (BR) was defined as fecal calprotectin (FCP) &amp;lt;250 μg/g. Descriptive statistics included the Chi-square and the Mann-Whitney U test. RESULTS Among the 100 included patients, 73 in IFX group vs. 27 in VDZ group, the mean age was 13 ± 4 years old, males were 68% (IFX) vs. 41% (VDZ) (P = 0.01). 49% had CD, 48% had UC, and 3% had unclassified IBD (IBDU). IFX- and VDZ-treated patients had similar Paris classifications. Baseline albumin levels (3.7 vs. 4.2 g/L, P&amp;lt;0.01) and steroid use (58% vs. 74%, P = 0.13) were lower in IFX vs. VDZ-treated patients. 12-month SFCR was 72% (49/68) and 71% (15/21) in IFX- and VDZ-treated patients, respectively (NS). Among SFCR at 12 months, BR was 59.62% (IFX) vs. 76.47% (VDZ), P = 0.21. Adverse events were rated as mild to moderate and occurred rarely in 8.22% (6/73) of IFX patients and in 7.41% (2/27) of VDZ patients (P = 0.89). These included an infusion reaction (1 in each group), elevated liver enzymes (1 in each group), infection (1), folliculitis (1), eczema (1), , and psoriasis (1). CONCLUSION We found both IFX and VDZ to have similar effectiveness in achieving SFCR and BR at 12 months when used as first-line agents for patients with uncomplicated mild-moderately active IBD. Prospective, larger head-to-head studies are needed for further validation. IFX group vs. VDZ group at the baseline. IFX group vs. VDZ group for Steroid Free Clinical Remission Patients at 12 months.

P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patients

Abstract Background After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF. Methods A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis. Results Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group. Conclusion In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.

P997 New Objective Assessment of perianal Crohn’s disease, Perianal Lesion Index; PLI

Abstract Background In the previous survey, decisions of biological treatment (Bio) success for perianal Crohn’s disease (pCD) were made by the patient’s subjective improvement and physician’s assessment, so it lacks objectivity. Moreover, physicians, surgeons, and proctologists are related to treating pCD. This aspect is the difficulty of the treatment of pCD. We need a common assessment for each area’s doctor. We aimed to develop a new objective assessment of pCD, including endoscopic findings, and assess the efficacy of the newly launched Bio except anti-TNFα agents for pCD. Methods Usually, perianal abscesses and fistula are derived from ulcers in the lower rectum and anal canal, so we adapted SES-CD to the location and checked discharge and needs of setons, and finally scored it (Table 1). We named this assessment Perianal Lesion Index; PLI. We retrospectively evaluated 20 pCD patients who received Ustekinumab (UST) and Vedolizumab (VDZ) from March 2017 to March 2023 at our institute. We checked each patient’s PLI, CRP, LRG, and CDAI and compared them before starting Bio and eight weeks after initiation of Bio using a paired T-test. Finally, we used the Pearson correlation coefficient to examine the correlation between PLI and conventional serum biomarkers and CDAI. Results The male-to-female ratio was 4.0, the average age at the treatment initiation was 35. Eighteen patient’s diseases were located in the small and large intestines, 10 patients were penetrating type, and 2 patients were stenotic type. We used UST for 16 patients and VDZ for 4 patients. Seven patients were naïve for Bio, 8 patients were treated by one Bio, and 5 patients were treated by two Bio.PLI was positively correlated with CRP (r=0.59, p&amp;lt;0.001) but not correlated with LRG (r=0.77, p=0.077) and CDAI (r=0.35, p=0.07). The pretreatment average PLI was 8.5 and significantly decreased to 3.9 (p&amp;lt;0.001) 8 weeks after Bio initiation. There was a significant change in CRP (3.1 to 0.9, p =0.03) but not CDAI (193 to 147, p=0.2). There were significant PLI changes in each treatment group; the UST group’s PLI change was 8.3 to 3.1 (p&amp;lt;0.001), and the VDZ group's PLI was 9.5 to 8.0 (p=0.02) (Figure 1). Conclusion PLI seems to be an objective assessment for pCD, and it was positively correlated to CRP. We could assess each drug’s efficacy for pCD. Further investigation is needed to establish PLI’s accuracy, and we hope this assessment will contribute to the choices of Bio for pCD and the evaluation of its efficacy

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP&amp;lt;5 mg/L and FC&amp;lt;250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

P592 Higher predictive power of epigenetic signatures for response to vedolizumab and ustekinumab in anti-TNF naïve patients with active Crohn’s disease

Abstract Background Despite the significant progress in IBD care with biological therapies, the current 'trial-and-error' method remains suboptimal. Previous results from our EPIC-CD study demonstrated that two distinct epigenetic panels of 25 and 68 DNA methylation markers, respectively, were associated with (non-)response to vedolizumab (VDZ) and ustekinumab (USTE) in active Crohn’s disease (CD)1. Data from clinical trials have demonstrated that response rates in patients naïve to biological treatment are higher. We therefore aimed to evaluate the performance of our models in bionaive and anti-TNF exposed subpopulations. Methods We prospectively measured peripheral blood DNA methylation profiles from 184 adult CD patients prior to treatment with VDZ or USTE in a discovery (n=126) and independent validation (n=58) cohort using the Illumina EPIC BeadChip array. Between 26 and 52 weeks, patients were categorized as responders or non-responders based on a combination of endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3-point drop in Harvey-Bradshaw Index (HBI) or HBI ≤4 AND no systemic steroids), and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Epigenetic biomarker identification and classification analyses were conducted through stability selection gradient boosting on the discovery cohort. Subsequently, the performance of the identified epigenetic biomarkers was assessed independently on the validation cohort, with patients stratified by prior anti-TNF exposure. Results Out of the 58 patients in the validation cohort, 25 received treatment with VDZ, and 33 with USTE, with 52% (n=13) and 36% (n=12) respectively naïve to anti-TNF treatment. Baseline characteristics between anti-TNF naive and anti-TNF exposed patients showed no significant differences, despite a slight significant age difference in the vedolizumab group, where anti-TNF exposed patients were significantly younger (table 1). In the overall independent validation cohort, the prediction models demonstrated an AUC of 0.75 for both VDZ and USTE. However, after stratification by prior anti-TNF exposure, we observed increased performance of our models among anti-TNF naive patients for both VDZ (AUCnon-exposed=0.85 versus AUCexposed=0.66) and USTE (AUCnon-exposed=0.97 versus AUCexposed=0.63 (figure 1). Conclusion Our findings demonstrate that prior anti-TNF exposure leads to somewhat reduced predictive power of our epigenetic models for Vedolizumab and Ustekinumab response. The predictive models may therefore find its optimal application in bio-naive patients, although they remain significant in anti-TNF exposed patients.

DOP17 Tofacitinib versus Vedolizumab Among Bio-naïve Patients With Ulcerative Colitis: A Real-World Propensity-Weighted Comparison

Abstract Background Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic naïve patients. There are sparse data comparing biologics with small molecules for IBD. We aimed to compare the efficacy, safety and persistence of tofacitinib and vedolizumab as the first advanced treatment for patients with UC. Methods Patients who received tofacitinib or vedolizumab as first advanced therapy for UC in NHS Lothian were included. We capped the upper age limit at 65 years to take into account regulatory guidelines for the use of JAKi as first line therapies across IMIDs. To allow treatment effect to be assessed outside of a randomized trial, we used inverse probability of treatment weighting (IPTW). This approach takes the probability of treatment assignment into account without potentially drastically reducing the analysable cohort size. The probability of treatment assignment was calculated via logistic regression using age, gender, IBD duration, Montreal extent, CRP, concomitant corticosteroids and partial Mayo score at drug commencement. Missing data for these variables were imputed using multivariate imputation by chained equations. Confounder-adjusted survival curves were created using Kaplan-Meier estimates weighted via IPTW. The Pepe and Fleming test was used to compare survival curves from drug commencement to day 1000 of treatment. Results We included 158 patients of whom 81 (51.2%) received vedolizumab and 77 (48.7%) tofacitinib. Median follow-up for patients on vedolizumab was 3.1 (1.6-4.8) years and for tofacitinib 1.5 (0.34-2.3) years. Baseline demographics were comparable except for disease extent (Table 1). At drug commencement there were no differences in steroid prescription (60.5% vedolizumab versus 57.1% tofacitinib), partial Mayo score, CRP or faecal calprotectin. At week 12, steroid free clinical remission was more frequent in the vedolizumab group (69% vs 51.4%, p=0.030) Figure 1B. Vedolizumab persistence was superior to tofacitinib (p=0.005) Figure 1A. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. There were no differences in the frequency of adverse events (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). However, adverse events resulting in temporary discontinuation of the drug occurred in 1 (1.2%) vedolizumab versus 11 (14.3%) tofacitinib, p=0.013. Conclusion We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bionaive UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy in UC.