Higher Rates Of Clinical Remission Research Articles

P0762 Early ustekinumab use improves clinical outcomes in biologic-naive Crohn’s Disease patients: A retrospective multicenter cohort study in Taiwan

Abstract Background Crohn’s disease (CD) is a progressive condition, and early treatment with infliximab combined with an immunosuppressant within six months has been shown to improve clinical outcomes. However, the impact of early ustekinumab (UST) use in biologic-naïve CD patients remains unclear. This study aims to address this gap by evaluating the clinical outcomes of early UST intervention in such patients. Methods In this retrospective cohort study, we included biologic-naïve CD patients treated with UST, with a clinical follow-up period of at least six months, from October 2020 to January 2024 across four medical centers in Taiwan. Patients who received UST within six months of CD diagnosis were categorized into the early-UST group, while the rest formed the control group. The primary endpoint was the improvement of clinical outcomes at six months. Results A total of 60 biologic-naïve CD patients were enrolled. Baseline characteristics were comparable between the two groups. At six months, the early-UST group (n=24) demonstrated significantly lower Crohn’s Disease Activity Index (CDAI) scores (73.03 vs. 112.42, p=0.038), lower Harvey-Bradshaw Index (HBI) scores (1.46±1.69 vs. 2.72±2.17, p=0.020), higher rates of clinical remission (91.7% vs. 63.9%, p=0.017), and higher rates of steroid-free clinical remission (79.2% vs. 50.0%, p=0.031) compared to the control group (n=36). Extending the evaluation to one year, the early-UST group continued to show lower CDAI scores (39.94 vs. 91.48, p=0.005). Adverse event rates were similar between the two groups. Conclusion Initiating ustekinumab within six months of CD diagnosis is associated with improved clinical outcomes and enhanced quality of life in biologic-naïve Crohn’s disease patients.

P0909 Efficacy of biologic therapy according to Crohn’s Disease location: a real-life observational study

Abstract Background The location of Crohn’s disease (CD) can affect evolution, disease monitoring, and management of patients. In daily practice, clinicians perceive a lower efficacy of therapies in ileal-dominant CD compared to other CD locations, but recent evidence is controversial. The primary aim of our study was to explore the efficacy of available biologic agents according to the main CD location in a real-life cohort of patients. Methods We retrospectively included all CD patients starting a biologic therapy at our IBD Centre from 2021 to 2023. In case of switch of therapy, the patient was reinserted and the endpoints re-evaluated. The efficacy was evaluated in terms of clinical remission (Harvey Bradshaw Index [HBI] <5) and clinical response (≥3 point decrease of HBI), endoscopic remission (Simple Endoscopic Score [SES-CD] <4), and response (≥2 point reduction of SES-CD), and ultrasound (US) response (resolution or improvement >25% of bowel wall thickening). Results We enrolled 127 consecutive CD patients under biologic therapy (75 males, mean age 49±15 years); 40 patients were treated with multiple lines of biologic therapy leading to a total of 181 cases analysed: 35 on Infliximab (IFX), 76 on Adalimumab (ADA), 19 on Vedolizumab (VDZ), 47 on Ustekinumab (USK) and 3 in dual therapy (VDZ+USK). Of these, 70 cases (39%) had an ileal-dominant CD (L1), while 111 (61%) had a colonic or ileocolic involvement (L2, L3). According to disease location, patients with an ileal-dominant CD showed a higher rate of clinical remission after the induction (59/68 [86.8%] ileal CD patients versus 77/106 [72.6%], p=0.028). Still, this difference was not maintained at W52 (53/62 [85.5%] versus 64/78 [82.1%], p=0.586). No difference was observed in clinical response. The clinical efficacy of different biologic therapies is shown in Table 1. USK was more effective in ileal patients, both after induction and at W52 (p=0.060). Moreover, a significantly higher clinical response was observed at W52 in ileal patients treated with ADA. No difference was observed in terms of endoscopic or US efficacy by CD location. During the observation period, ileal CD patients showed a higher rate of clinical flare-up (27/42 [38.6%] versus 21/105 [20.0%], p=0.007). However, the hospitalization and surgery rate was similar. Globally, the discontinuation rate was 71/181 (39%) after a mean time of 14 months, in 54 cases for inefficacy (18 in ileal CD versus 36, p=0.33). Conclusion The ileal-dominant location of CD does not seem to significantly affect the efficacy of biologic agents in a real-life cohort of CD patients. Among the available therapies, USK and ADA seem to show a slight clinical advantage in managing the ileal forms compared to other biologics.

P0502 Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis: 3-year and 5-year follow-up

Abstract Background Endoscopic healing in patients with ulcerative colitis predicted higher rates of clinical remission at 12 months follow-up. Meanwhile, active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis was associated with relapse. [1] We aim to evaluate the impact of baseline endoscopic and histological healing on long-term clinical relapse as well as the rates of UC-related emergency room (ER) visits, hospitalizations and surgery. Methods This prospective observational study was conducted at the Inflammatory Bowel Disease (IBD) Centre of McGill University Health Centre (MUHC) July 2012 to July 2020 and included all adult UC patients undergoing a colonoscopy with biopsies for disease assessments. Patient must have been in clinical remission with a stable dose of medication for at least 3 months prior to enrolment. Patients were followed every 3 months in the first year then every 6-12 months to assess disease relapse, defined as a partial Mayo score (PMS) >2. Active endoscopic disease was defined as Mayo endoscopic score (MES) of 2 or 3. Active histological disease was defined as a Geboes score ≥3.1 (epithelial neutrophils with or without crypt destruction/erosions). Results A total of 253 patients were included in this study. At the 3-year follow-up, baseline active endoscopic and histological disease did not predict clinical relapse. However, baseline endoscopy with a EMS of 0 (compared to 1-3) showed a trend towards significance in predicting relapse (P = 0.08). Multivariate analysis adjusting for age, gender, height, and smoking status remained non-significant (P = 0.0837, 95% CI 0.29–1.08). At 5 years, baseline histological activity did not predict risk of clinical relapse, however, endoscopy with EMS 0 significantly predicted clinical relapse (P = 0.0080), with multivariate analysis confirming this (P = 0.0110, 95% CI 0.27–0.84). Baseline endoscopy with EMS 1-3 was linked to increased ER visits at 3 years (P = 0.02), but not at 5 years (P = 0.7618). Histological disease activity was not linked to increased ER visits at 3 and 5 years. Neither baseline endoscopy nor histology predicted the risk of hospitalisation or surgery at either follow-up (P > 0.05). Conclusion Active histologic disease did not predict long-term clinical relapse at 3- or 5-years point. On the other hand, baseline endoscopic activity of EMS of 0 compared to 1-3, only predicted clinical relapse at 5 years and IBD-related ER visits at 3 years. This long-term follow up data questions the additional role of histology in patient with complete endoscopic healing.

DOP008 High clinical and endoscopic remission rate with Vedolizumab in early CD patients: the 2nd interim analysis from a prospective multicenter interventional Study (EARLY CD)

Abstract Background Early treatment with advanced therapy prior to the development of complications such as stricture and fistula, is associated with better disease prognosis in patients (pts) with Crohn’s disease (CD). This study (EARLY CD) aims to evaluate the efficacy and safety of Vedolizumab (VDZ) as first line therapy in pts with early CD. Methods EARLY CD is a prospective, single-arm, multicenter, interventional study (ChiCTR2200063233). Target enrollment was 172 pts and all pts will receive up to 50 weeks of VDZ treatment with dose optimization (additional dose at week 10 if no clinical response, and switch to Q4W if secondary loss of response at maintenance). Main inclusion criteria for early CD are disease duration less than 18 months, no previous use of immunosuppressive agents and advanced treatment, no complications such as fistula or stricture (except for inactive perianal fistula). Primary endpoint was clinical and endoscopic remission at week 52, together with several secondary endpoints including clinical and endoscopic response, transmural healing assessed by MRE, and improvements in both PRO and QoL. This second interim analysis was conducted when all 172 enrollments were completed. Results 172 pts were recruited with a median follow-up of 7.1 months (IQR 3.3-11.7). Mean age was 30.9 years, 73.8% were male. Mean CDAI score at baseline was 245.97 and SES-CD score was 9.7 (table). Clinical and endoscopic remission rates reached 83.8% and 48.7% at week 14, with further increase to 92.1% and 71.1% at week 52 (figure). Early clinical improvement was observed, with both abdominal pain score (APS) and loose stool frequency score (LSFS) started to decline from week 1, APS decreased by 50.6% (from 44.9 to 22.2), LSFS decreased by 56.1% (from 32.5 to 14.26). From week 1 to week 52, IBDQ improved from 157.8 to 185.9, self-rated health status EQ visual analogue scale increased from 72.3 to 85.4, and self-reported fatigue score assessed by FACIT improved from 38.1 to 43.9. Twenty pts have completed MRE evaluation both at baseline and week 52, with MaRIA score showing a decline from 23.9 to 20.3. Adverse events occurred among 20 pts (11.6%), including exacerbation of perianal disease that required surgical drainage (n=6), arthralgia (n=4), infection (n=7), GI bleeding (n=1), acute appendicitis (n=1), and elevated transaminase (n=1). Conclusion This is the first study worldwide to prospectively evaluate the efficacy of VDZ as first-line therapy among bio-naïve pts with early CD. Interim analysis showed promising results including high clinical and endoscopic remission rates through week 52, together with early PRO response and improvement in quality of life.

P0800 Efficacy of filgotinib in patients with ulcerative colitis refractory to prior biologics

Abstract Background Filgotinib has shown promise for patients with moderate-to-severe Ulcerative Colitis (UC) who are refractory to prior biologics. Given the need for effective alternatives in this challenging patients, this study examines the efficacy of filgotinib in biologic-refractory patients. Methods An observational, descriptive, ambispective, single-center study of 29 patients with active UC who were started on filgotinib 200mg/24h between October 2018 and May 2024. Clinical and biochemical variables analyzed: partial Mayo Score (PMS), endoscopic evaluation, fecal calprotectin (FC) and the adjuvant treatment-free response (corticosteroids or apheresis) at weeks 8, 16, 26 and 52. Other variables were also measured: disease characteristics, previous biologic treatments and concomitant use of corticosteroids and immunomodulators. Results The median age was 43 (IQR 32-53) years, 45% were women. The median disease duration was 7 (IQR 3-14) years. One patient smoked at the beginning of treatment, and ten were ex-smokers. 45% had extensive colitis (E3, according to Montreal classification), and 55% had left-sided colitis. In 13 patients, colonoscopy was performed prior to drug initiation, with 92% presenting an endoscopic Mayo score 2-3. The most unique feature of our cohort is the high refractoriness to previous biologic treatments. Only one patient was naïve to biologics, as he was not a candidate for anti-TNF due to a history of multiple sclerosis. Of the remaining 28 patients, the majority (97%) had failed anti-TNF treatment, 41% had also failed ustekinumab and 34% had failed vedolizumab. At the time of treatment initiation, 45% were receiving concomitant oral or intravenous corticosteroids. In terms of baseline disease activity, the median PMS was 6 (IQR 5-7), and the median FC was 2000 (IQR 1664-2000) µg/g. Median follow-up was 26 (8-52) weeks. At weeks 8, 16, 26 and 52, the clinical response (PMS reduction ≥2) and clinical remission (PMS ≤1) rates were 83%/45%, 80%/64%, 72%/56% and 62%/47%, respectively (image 1). There was a significant decrease in FC: 1124 (IQR 155-2000) µg/g, 860 (IQR 53-2000) µg/g, 187 (IQR 82-1107) µg/g and 165 (IQR 17-1910) µg/g at weeks 8, 16, 26 and 52, respectively. Adjuvant treatment-free response was 43% with an estimated Kaplan-Meier curve persistence of 48% at 1 year (image 2.1). During follow-up, filgotinib was discontinued in 7 patients, 4 of them in the first 8 weeks. Attached is the Kaplan-Meier curve for the persistence of Filgotinib (image 2.2) estimated at 72% at 1 year. Conclusion Filgotinib is effective in the treatment of biologic-refractory ulcerative colitis in selected patients, achieving a high clinical remission rate and significantly reducing the need for adjuvant treatment.

Upadacitinib induction is effective and safe in ulcerative colitis patients including those with prior exposure to tofacitinib: a multicenter real-world cohort study.

Upadacitinib is a novel selective Janus kinase inhibitor approved for use in ulcerative colitis. Clinical trials had rigorous criteria and excluded many patient subgroups. Given limited real-world effectiveness data, we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population. Patients that commenced upadacitinib for moderate-to-severe ulcerative colitis from September 2022 until March 2023 were identified at 13 inflammatory bowel disease centers across Australia. Clinical, biochemical, endoscopic, and intestinal ultrasound outcomes were recorded retrospectively at baseline, week 8, and week 16. One hundred and fifty-two patients (61 female [40%], median age 38 years [interquartile range, 28-50]) were included. The primary endpoint of clinical remission was met in 79% at week 8, and 84% at week 16. A total of 42 patients (28%) with prior tofacitinib exposure were included. No significant difference in clinical remission was observed by week 16 between tofacitinib experienced compared to tofacitinib naïve patients (86% vs. 84%, P= 0.67). Complete intestinal ultrasound data was available for 36 patients, showing transmural remission in 64% at week 8 and 81% at week 16, with a decrease in median bowel wall thickness of 2.3 mm and 2.4 mm, respectively. Upadacitinib resulted in high rates of clinical remission at 8 and 16 weeks in this large real-world cohort of ulcerative colitis patients. Upadacitinib is effective in patients with prior tofacitinib exposure. Intestinal ultrasound shows significant rates of transmural remission at week 8, sustained through week 16.

Risankizumab Concentration but not IL-22 Levels Are Associated With Clinical and Biochemical Remission in Patients With Crohn’s Disease

Risankizumab (RZB) is a monoclonal antibody that targets the p19 subunit of interleukin (IL)-23.1 The ADVANCE and MOTIVATE randomized controlled trials (RCTs)2 demonstrated that intravenous (IV) RZB compared with placebo led to higher rates of clinical remission and endoscopic response at week 12 in patients with active Crohn's disease (CD).2 The phase III FORTIFY RCT showed that subcutaneous (SC) RZB was significantly more effective than placebo for achieving clinical remission and endoscopic response as maintenance therapy in patients with moderate-to-severe active CD.3.

Efficacy of the Craniopharyngioma Resection via Expanded Endoscopic Endonasal Transsphenoidal Approach in the Treatment of Complex Craniopharyngioma and Its Effect on Pituitary Function and Complications of Patients.

Surgical resection is the most effective method for craniopharyngioma, with complex operations and a high incidence of complications, especially for complex craniopharyngioma. The study focuses on selecting a proper surgical method to treat complex craniopharyngioma. A clinical study was conducted in this direction to explore the efficacy of expanded endoscopic endonasal transsphenoidal approach (EETS) and transcranial approach (TCA) in the treatment of complex craniopharyngioma and their effects on pituitary function and complications of patients. The clinical data of 73 patients with complex craniopharyngioma in Baoding No.2 Central Hospital from December 2017 to December 2022 were retrospectively analyzed. 13 patients who did not meet the admission criteria were excluded, and 60 patients were finally included. The included patients were divided into the TCA and EETS groups according to the treatment method. The surgical conditions, total tumor resection rate, clinical remission rate, and complications of patients in two groups were compared. The pituitary function of all patients, including thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and human growth hormone (hGH), was compared. A total of 60 patients were finally included in the study, including 30 cases in the EETS group and 30 cases in the TCA group. The two groups had no statistical difference in baseline demographic characteristics and pathological types (p > 0.05). Compared with the TCA group, the EETS group had less intraoperative blood loss, operation time, tumor resection time, and hospitalization time (p < 0.001) and had a significantly higher total tumor resection rate and clinical remission rate (p < 0.05). The EETS group had higher ACTH and hGH levels than the TCA group (p < 0.05). There was no statistical difference between the two groups incidence of complications and disease recurrence rate (p > 0.05). The craniopharyngioma resection via EETS has a significant therapeutic effect in complex craniopharyngioma with a high total tumor resection rate and clinical remission rate, which can protect the pituitary function of patients and provide more benefits for patients.

Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure

Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849]; U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease (CD). Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg (UPA15), or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. GOV: NCT03345849, NCT03345836, NCT03345823.

Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.

Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers. The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis. Studies were identified through a search of the PubMed database from the National Library of Medicine. We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years. Studies examining pharmacologic and select nonpharmacologic interventions were included. Outcomes measures included clinical, endoscopic, and histologic end points. Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain. Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes. Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease—EXVEDOCOL

BackgroundReal-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. MethodsEXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. ResultsThirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. ConclusionsHigh clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

P922 A multicenter retrospective real-world study to determine the optimal cases of vedolizumab-treated UC patients

Abstract Background Vedolizumab (VDZ) is a gut-selective monoclonal antibody approved for ulcerative colitis (UC). This real-world study aimed to evaluate the effectiveness of VDZ in the treatment of UC, with the goal of further treatment optimization. Methods In this multicenter, retrospective, observational chart review, 370 patients with UC who received at least one dose of VDZ in clinical practice at 16 tertiary hospitals in Japan were enrolled. Comprehensive analyses of predictors of 2- and 54-week remission, drug persistence, and the development of loss of response were performed. Results Lower partial Mayo scores and lower Mayo endoscopic subscores were significantly associated with 2-week remission in the multivariate analysis. More 2-week remitters achieved clinical remission at Week 52 than non-2-week remitters. Clinical remission rates were significantly higher in biologic-naïve than in biologic-non-naïve patients across Weeks 2 to 54. Higher clinical remission rates at Week 54 were significantly associated with lower baseline disease severity and no prior anti-tumor necrosis factor alpha (anti- TNFα) treatment. Among patients with prior anti-TNFα treatment, longer duration of anti-TNFα treatment was associated with higher clinical remission rates at Week 54 (28.1%, 32.7%, and 60.0% for ≤3 months, &amp;gt;3 to &amp;lt;12 months, and ≥12 months, respectively, p=0.001 between groups). In addition, clinical remission rate at Week 54 was higher in patients who had loss of response to anti-TNFα treatment than in those who had primary nonresponse (54.4% vs 24.6%; p=0.001). The 54-week persistence rate was 64.5%. Concomitant use of tacrolimus (OR 2.76, 95% CI 1.00, 7.62, p=0.05) and shorter disease duration (median:7.8 years), (OR 0.33, 95% CI 0.13, 0.82 for ≥7.8 years vs &amp;lt;7.8 years p=0.017) were associated with loss of response to VDZ in the multivariate analysis, but prior use of anti- TNFα treatment was not. Conclusion This retrospective study confirms favorable outcomes with VDZ in patients without prior exposure to anti-TNFα treatment. However, among patients with history of anti-TNFα- exposure, better outcomes were observed among those who experienced loss of response than those with primary nonresponse, as well as those who had a longer duration of anti-TNFα treatment.

OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

P919 Crohn’s Disease Exclusion Diet as add-on therapy in refractory pediatric patients

Abstract Background Despite the accumulating body of evidence of the efficacy and tolerability of Crohn’s disease exclusion diet (CDED) combined with partial enteral nutrition (PEN), there is still a paucity data regarding its use in combination with other medical treatments. We aimed at assessing its efficacy in re-inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies. Methods This was a single-center, retrospective, observational study conducted at an Italian national referral pediatric IBD center. Incident patients who received CDED coupled with PEN in the setting of the loss of response to other maintenance therapies from January 1st, 2020 to June 30th 2023 were included. Clinical remission at the end of each phase was defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) below 12.5. Biochemical remission was defined by a c-reactive protein (CRP) lower than 0.5 mg/dL. A FC lower than 150 mg/kg was used as a surrogate of mucosal improvement (MI). Results 25 patients (52% males) met inclusion criteria and were included in the analysis. Median disease duration at CDED+PEN initiation was 31 months (Q1-Q3: 8.4-13.8). The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti-TNF-alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Table 1). wPCDAI, CRP and FC significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p&amp;lt;0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission, 15 (60%) patients had CRP levels within normal range and 7 (28%) of them had normalized FC. 18/25 patients (72%) had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of &amp;lt; 12.5 after a complete course of EEN) were more likely to achieve clinical remission when receiving CDED + PEN (11/13 vs 1/5, p=0.022). Conclusion CDED coupled with PEN is a valid treatment strategy in the setting of secondary loss of response to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “nutritional responder” patients.

DOP54 Guselkumab and golimumab combination induction therapy in Ulcerative Colitis results in early local tissue healing that is sustained through guselkumab maintenance therapy

Abstract Background Combination induction therapy with guselkumab (GUS), an interleukin (IL)-23p19 subunit antagonist, and golimumab (GOL), a tumor necrosis factor (TNFα) antagonist, induced higher rates of clinical remission, endoscopic, and histologic outcomes than either monotherapy at Week (WK)12 in patients (pts) with ulcerative colitis (VEGA NCT03662542). Data through WK38 suggested the continued benefit of combination induction even after a transition to GUS monotherapy at WK12. We explored early molecular changes in colon tissue in a subset of pts at WK4 to define mechanistic contributions of each monotherapy and combination; these parameters were evaluated again at WK38 to assess potential carry-over of efficacy. Methods Colon biopsies were obtained at baseline (n=195), WK4 (n=42 substudy), and WK38 (n=172). Transcriptional profiles were generated with RNA sequencing (RNAseq). Gene correlation network analysis was applied in conjunction with publicly available single cell RNAseq data to define biologically relevant bulk and cell type-specific transcriptional modules associated with molecular features of disease. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment. Results At WK4, combination induction (n=10) showed significant (p&amp;lt;0.05) decreases in molecular features compared to GUS (n=19) and GOL (n=13), including transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement at WK4 (Mayo endoscopy subscore of 0 or 1) (combination 5/11, GOL 1/13; GUS 2/19). Reduction (p&amp;lt;0.05) in inflammatory modules persisted through WK38 with combination vs monotherapy induction. Module changes between treatments at WK4 indicated a stronger correlation between GUS and combination (R=0.8; p=2.2e-16) than GOL and combination (R=0.52; p=4.1e-12), with processes associated with epithelial and stromal biology, and mucosal inflammation. In contrast, the combination effect on specific neutrophil/myeloid biology at WK4 was more similar to GOL than GUS, supporting the early role of GOL in targeting innate inflammation. Conclusion Combination induction with GUS and GOL showed significant reductions in major inflammatory features of disease as early as WK4 which persisted through WK38 with GUS maintenance. Correlative analysis supports the role of GUS as the primary driver of tissue healing, with GOL further contributing to innate inflammatory activity, which demonstrate differential and complementary mechanisms of action of TNFα and IL-23p19 subunit blockade.

P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial

Abstract Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing &amp;lt;80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score &amp;lt;150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.

Early intervention with Ustekinumab is associated with higher rates of clinical and endoscopic remission in patients with Crohn’s disease

Background: Early biologic intervention after diagnosis has shown improved clinical and endoscopic outcomes in patients with Crohn’s disease (CD), while very little is known about the effectiveness of early versus late administration of Ustekinumab (UST). Objectives: We aimed to compare early versus late UST use in managing CD and identify potential predictors associated with clinical and endoscopic outcomes. Design: This was a retrospective observational study. Methods: This study included patients with CD who started UST treatment from 2020 to 2023 in our center. Clinical and endoscopic outcomes were compared between early stage (⩽24 months) and later-stage (&gt;24 months) groups at 6 months after starting UST therapy, and clinical predictors associated with any of the outcomes were assessed by logistic regression model. Furthermore, time-to-event analyses were applied to observe CD-related prognosis during follow-up. Results: This study included 237 patients with CD, with 44.3% ( n = 105) starting UST at the early stage and 55.7% ( n = 132) at the later stage. Patients with early UST use demonstrated significantly higher rates of clinical and endoscopic remissions as compared to those with late UST use at 6 months after treatment. After adjusting for disease-related factors using multivariate logistic regression analysis, active perianal disease and severe disease were negatively associated with clinical and endoscopic remission in both early and late UST use groups. Finally, early UST administration was associated with a more favorable long-term outcome in terms of overall hospitalization and treatment escalation during follow-up. Conclusion: Starting UST therapy in the early stage of CD especially within the first 6 months was associated with high rates of clinical and endoscopic remission and a low rate of CD-related complications.

Inflammatory mesenteric fat detected by Intestinal ultrasound is correlated with poor long-term clinical outcomes in patients with Crohn's disease

BackgroundData on the correlation between inflammatory mesenteric fat (i-fat), detected by intestinal ultrasound (IUS), and the prognosis of Crohn's disease (CD) remains limited. AimsTo investigate the impact of IUS-detected i-fat on long-term clinical outcomes. MethodsWe retrospectively enrolled 171 active CD patients who initiated infliximab. Clinical remission (CR), mucosal healing (MH) and transmural healing (TH) were assessed at week-14 and 1 year. ResultsBaseline i-fat was detected in 107 patients, while 64 without i-fat. At week-14 and 1 year, patients with i-fat showed lower rates of CR (61.7% vs. 87.5%; 62.3% vs. 86.7%), MH (20.6% vs. 46.9%; 38.6% vs. 65.0%) and TH (10.3% vs. 31.3%; 21.6% vs. 51.7%), compared to those without (all p<0.01). Multivariable analysis revealed that baseline i-fat was a negative predictor for CR (OR=0.212) and MH (OR=0.425) at week-14, and CR (OR=0.340) and TH (OR=0.364) at 1 year (all p<0.05). At week-14, 56 patients with baseline i-fat recovered to without i-fat. Patients with i-fat recovery had higher rates of CR (86.8% vs. 23.1%), MH (58.5% vs. 7.7%) and TH (34.0% vs. 2.6%) at 1 year than those with i-fat at week-14 (all p<0.001). ConclusionIUS-detected i-fat correlated poor long-term clinical outcomes in CD with infliximab.

Efficacy of early biologic therapy versus late/conventional therapy in children and adolescents with Crohn's disease: A systematic review and meta-analysis.

The objective of this study was to estimate the effectiveness of early biologics compared to conventional treatment in the management of Crohn's disease among pediatric and adolescent patients. A comprehensive literature search was conducted in four electronic databases to identify relevant studies published from inception to 2023. The inclusion criteria comprised randomized controlled trials (RCTs) and cohort studies that reported on the efficacy and clinical outcomes of early biologic therapy compared to late/conventional therapy in children with Crohn's disease. The quality of the studies was assessed using the Cochrane Risk of Bias tool and the Newcastle Ottawa scale. A total of 13 studies (2 RCTs and 11 cohort studies), involving 861 patients, were included in the meta-analysis. The results demonstrated that early biologic therapy was associated with a significantly higher rate of clinical remission (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.10-1.54), lower relapse rates (RR 0.33, 95% CI 0.21-0.53), and improved mucosal healing (RR 1.47, 95% CI 1.10-1.97) compared to late/conventional therapy. However, it should be noted that there was evidence of publication bias among studies reporting clinical remission. In conclusion, early biologic therapy is significantly more effective in achieving clinical remission (within two years of diagnosis), promoting mucosal healing, and reducing relapse rates in pediatric and adolescent patients with Crohn's disease, compared to late/conventional therapy. These findings emphasize the importance of initiating biological therapy early in the treatment of Crohn's disease in this patient population.