Endoscopic Outcomes In Patients Research Articles

Safety of Endoscopic Procedures in Thrombocytopenia and Neutropenia: Embracing Assurance.

Few studies have evaluated the post-endoscopic adverse events in patients with neutropenia and thrombocytopenia. Current guidelines do not provide clear direction on this topic. We explore the pooled rates of safety and adverse effects of endoscopic interventions in thrombocytopenia and neutropenia patients via a systematic review & meta-analysis. Databases, including Medline, Scopus, and Embase, were searched (in May 2023) using specific terms for studies evaluating the clinical outcomes of endoscopy in patients with thrombocytopenia and neutropenia. Standard meta-analysis methods were employed using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. Six studies and four studies evaluated endoscopic outcomes in patients with thrombocytopenia and neutropenia respectively with mean age was 56years. The pooled rate of total post-biopsy bleeding and total post-polypectomy bleeding among patients with thrombocytopenia was 4% (95% CI 1-11), I2 = 84%, and 12% (95% CI 3-36) I2 = 43%. The total rate of post procedure-related bleeding in thrombocytopenia was 5% (95% CI 1-14) I2 = 95%. The pooled rate of post-endoscopic infection (fever from any cause, bacteremia) in neutropenia was 10% (95% CI 3-28%) I2 = 96%. On sub analysis, the pooled rate of bacteremia and 30days all-cause mortality in neutropenia was 4% (95% CI 3-5%) I2 = 0% and 13% (95% CI 4-34%) I2 = 95% respectively. Our data supports the notion that endoscopic procedures are safe for neutropenic, thrombocytopenic patients with suitable indications and reasonable functional status and have an acceptable risk/benefit ratio.

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.

A276 A SYSTEMATIC REVIEW OF THE ASSOCIATION BETWEEN EOSINOPHILIC ESOPHAGITIS AND INFLAMMATORY BOWEL DISEASE

Abstract Background Inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) are chronic inflammatory conditions of the gastrointestinal tract. IBD and EoE have been linked to other autoimmune conditions. There has been conflicting evidence on whether these two diseases are associated. Aims The purpose of the current study is to perform a systematic review evaluating the incidence of co-existing IBD and EoE. To determine whether the relationship between IBD and EOE is unique for autoimmune conditions, we also evaluated the relationship between other autoimmune conditions such as rheumatoid arthritis and atopic dermatitis and EOE. Methods A comprehensive search strategy was conducted on July 10, 2023 using MESH terms for eosinophilic esophagitis and IBD, autoimmune disorders or connective tissue disorders in Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews (Ovid); and Cochrane Central Register of Controlled Trials (Ovid). The primary outcome was defined as the frequency of concomitant IBD and EOE compared to the frequency of IBD alone. Secondary outcomes included the frequency of concomitant autoimmune conditions and EOE compared the frequency of the autoimmune condition alone, as well as the examination of clinical, biomarker, and endoscopic outcomes of patients with concomitant IBD and EOE compared to patients with IBD alone. Five independent reviewers participated in study selection applying eligibility criteria and selecting studies for inclusion. Duplicate items were removed and title and abstracts screening occurred. Any publication deemed potentially relevant by was carried forward to the full-text review. Discrepancies were resolved by consensus. Results Our systematic search identified 2144 potential studies. After screening titles, we were left with 268 studies. Following full text review, 50 studies remained which included 9 articles and 19 abstracts on IBD and EOE, and 8 articles and 14 abstracts on other autoimmune conditions and EOE. The 9 articles on IBD and EOE consisted of 6 retrospective cohort, 1 prospective cohort, 1 case-control and 1 case series study. 8 of the studies were conducted in the United States and 1 was conducted in Italy. There were 4 studies on adult populations, 4 studies on pediatric populations, and 1 study in both. There was a total of 133,451,249 patients evaluated, the majority being from one study (n=133,308,339 patients). The number of concomitant IBD and EOE patients per study ranged from 5 to 3506 patients and the number of IBD patients without EOE ranged from 33 to 701,601 patients. In the general population, the number of EOE patients alone per study ranged from 33 to 102,048. Completion of data extraction and statistical analysis is ongoing. Conclusions There may be an association between IBD and EOE. Further data analysis is ongoing. Funding Agencies None

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

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

P886 Ustekinumab concentrations in induction are associated with mid-term endoscopic outcomes in patients with inflammatory bowel disease

Abstract Background It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies. Methods We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index <5 and a partial Mayo score <2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS. Results We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates. Conclusion In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.

S1142 Impact of Guselkumab Therapy on Histologic and Combined Histologic and Endoscopic Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Week 12 Results From the Phase 3 QUASAR Induction Study

S1142 Impact of Guselkumab Therapy on Histologic and Combined Histologic and Endoscopic Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Week 12 Results From the Phase 3 QUASAR Induction Study

Characteristics and Risk Factors of Upper Gastrointestinal Bleeding in Patients on Antithrombotic Therapy: A Prospective Study

Study aims: Evaluate the effect of antithrombotic therapy use on endoscopic outcomes in patients admitted for upper gastrointestinal bleeding. Patients and Methods: This is a prospective monocentric cross-sectional study of 332 patients conducted between June2020 and August 2021.We considered as users of AT drugs all patients on antiplatelet agents (low-dose aspirin, thienopyrimidines) and/or anticoagulants (vitamin K antagonists, direct-acting anticoagulants, heparin). Results: The average age was 59+/−16.7 years. Our series was characterised by a clear male predominance of 77.1%.63 patients (19%) were taking AT drugs (41 antiplatelet, 39 anticoagulant). The two groups differed in age (68 vs 57; p<0.001), comorbidities (75.8% vs 16.7%; p<0.001), however there was no statistically significant difference in active bleeding at endoscopy (12.7%vs 16.8%; p=0.425), and the need for endoscopic haemostasis (7.9%vs 16%; p=0.1).In multivariate analysis and adjusting for age, sex, comorbidities, presence of active bleeding and use of antithrombotics, only the presence of active bleeding could predict the need for endoscopic haemostasis. Indeed, the presence of active bleeding at the time of endoscopy multiplies by 26 the risk of recourse to endoscopic haemostasis (OR: 26, CI: 12.9–62.15, p<0.001), whereas the use of AT drugs does not influence the need for endoscopic haemostasis (OR: 0.386, CI: 0.105- 1.42, p=0.154). Conclusions: Older patients using AT admitted for UGIB do not appear to have an increased risk of active bleeding at endoscopy or needing endoscopic haemostasis.

Sarcopenia is a negative predictive factor for endoscopic remission in patients with Crohn's disease treated with biologics.

Sarcopenia has been associated with poor prognosis in chronic diseases. To investigate the role of sarcopenia in predicting clinical and endoscopic outcomes in patients with Crohn's disease (CD). Consecutive CD patients who started biologics between 2014 and 2020 and underwent abdominal magnetic resonance or computed tomography within 6 months from the beginning of the biological therapy were enroled. Sarcopenia was defined as Psoas Muscle Index (PMI) lower than 5.4 cm²/m² (men) and 3.56 cm²/m² (women). Univariate and multivariate analyses were used to evaluate whether sarcopenia could predict steroid-free clinical remission (SFCR), endoscopic remission (ER), hospitalisation and surgery after 12 months of therapy. 358 patients were included. Sarcopenia was found in 18.2% of patients, and it was associated with a lower rate of ER (14.8% vs 47.7%; p=0.002) after 12 months of therapy, while it was not associated with SFCR (65.1% vs 70.1%; p=0.435), hospitalisation (9.2% vs 7.8%; p=0.801) and surgery (3.1% vs 6.1%; p=0.549). Sarcopenia was identified as a predictor of lack of ER (odds ratio [OR]=5.2; p=0.006), as well as smoking (OR=2.5; p=0.028) and perianal disease (OR=2.6; p=0.020). Sarcopenia is a negative prognostic factor for ER in CD patients treated with biologics.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy

OP17 Upadacitinib Improves Endoscopic Outcomes in Patients with Moderate to Severely Active Crohn’s Disease Irrespective of Previous Failure to Respond to Biologics or Conventional Therapies

Abstract Background Upadacitinib (UPA), an oral, reversible JAK inhibitor, demonstrated superior efficacy compared to placebo (PBO) in patients with moderate to severe Crohn’s disease (CD) in 2 multicentre, phase 3 induction (U-EXCEL and U-EXCEED), and 1 maintenance (U-ENDURE) trial.1-3 This sub-analysis assessed endoscopic outcomes in patients with or without a history of biologic failure (inadequate response or intolerance) among those receiving UPA treatment. Methods Eligible patients had average daily stool frequency [SF] ≥4 and/or abdominal pain score [APS]≥2, plus a Simple Endoscopic Score for CD (excluding the presence of narrowing component) ≥6 [≥4 for isolated ileal disease]). Patients received UPA 45 mg once daily (QD; UPA45) or PBO (2:1) for 12 weeks (wks). Patients that achieved SF/APS clinical response after 12 weeks of treatment with UPA45 (≥ 30% decrease in daily very soft/liquid SF and/or ≥ 30% decrease in daily abdominal pain APS with neither worse than baseline) were re-randomized (1:1:1) to UPA 30 mg QD (UPA30), UPA15 mg QD (UPA15) or PBO for 52 wks of maintenance. Endoscopic response\ remission were evaluated by central reading at wk 12 induction and wk 52 maintenance. Adverse events (AEs) were assessed through wk 52. Statistical significance in comparisons was not assessed due to an inability to control for type I error in subgroup analysis. Results Baseline characteristics/demographics were similar across treatment groups. In the pooled induction population (U-EXCEED+U-EXCEL), 72.0% UPA45 and 71.5% PBO patients had history of prior biologic failure. In U-ENDURE, 73.4% UPA15, 75.6% UPA30, and 76.4% PBO patients had history of prior biologic failure. In patients without or with biologic failure, UPA demonstrated higher rates for endoscopic response compared to PBO at wk 12 (52.0%, 35.7% UPA45 vs 16.2%, 5.3% PBO, Figure 1A) and wk 52 (Figure 1B). Similarly, in patients without or with a history of biologic failure, UPA exhibited higher rates of endoscopic remission at wk 12 (36.0%, 19.6% UPA45 vs. 10.1%, 2.8% PBO, Figure 1A) and wk 52 (Figure 1B). Differences from PBO were found in endoscopic response or remission in patients that remained in response/remission from the entry of maintenance to wk 52 for either dose, regardless of prior history of biologic failure (Figure 1C). UPA treatment was well-tolerated, with no new safety risks observed compared to the known safety profile of UPA (Tables 1-2). Conclusion Upadacitinib achieved clinically meaningful endoscopic outcomes, which were maintained up to 1 year, irrespective of a patient’s prior biologic treatment, with an acceptable safety profile.

P153 Association between ustekinumab trough concentrations and clinical, biochemical, and endoscopic outcomes in patients with Inflammatory Bowel Disease

Abstract Background Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn’s disease (CD) and ulcerative colitis (UC). There is limited data on therapeutic outcomes and UST trough levels (UTL). We aimed to evaluate the association between UTL and corticosteroid-free clinical remission. We also assessed the relationship between UTL and endoscopic remission as a secondary outcome. Methods We performed a cross-sectional study on IBD patients receiving maintenance therapy with UST (>6 months). We included UTL, C reactive protein (CRP), faecal calprotectin (FC), and clinical and endoscopic indexes (Harvey Bradshaw [HBI] and simple endoscopic score [SES-CD] for CD patients; and partial Mayo score [PMS] and endoscopic Mayo score [EMS] for UC patients). Corticosteroid-free clinical remission (CSF-CR) was defined as HBI<5 or PMS<2 plus normal CRP and/or FC values without corticosteroids. Endoscopic remission was defined as SES-CD<3 or EMS<2. Results We included 105 patients; the mean age was 50 years, and 59% were female (Figure 1). Eighty-seven patients had CD, and 92% had previously received an anti-TNF. The median time on UST was 121 weeks at inclusion. Sixty-four patients received 90mg subcutaneous (SC) every 4 weeks, 40 patients 90mg SC every 8 weeks, and 1 patient 90mg SC every 12 weeks. Eighty percent were in CSF-CR, and 53% were in endoscopic remission. Median UTL were 2,7µg/mL (IQR: 1,7-4,1µg/mL); UST antibodies were not detected. Patients in CSF-CR and endoscopic remission did not show significantly higher UTL (3,4µg/mL vs. 2,5µg/mL, p=0,147; and 3,6µg/mL vs. 3,7µg/mL, p=0,903, respectively). No differences in UTL were detected between patients on monotherapy and combination therapy (2,9µg/mL vs. 3,3µg/mL, p=0,456). Conclusion No association between UTL and clinical or endoscopic activity was observed in our predominantly biologic-experienced cohort. Further prospective studies are needed to determine the role of therapeutic drug monitoring while on UST.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy

BackgroundIn spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. MethodsPatients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. ResultsOut of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48–234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5–187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. Conclusions5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids.

BackgroundIdentifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS).ObjectiveEvaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS.MethodsA retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS.ResultsA statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p<0.05). However, only a statistically significant difference was found in the 4-weeks postoperative LKS when comparing between treatment groups (p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015).ConclusionIn AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a short-term improvement in endoscopic scores.

Shenling Baizhu San ameliorates ulcerative colitis by regulating the gut microbiota and its tryptophan metabolites: A complementary medicine to mesalamine

Ethnopharmacological relevanceShenling Baizhu San (SBS) is commonly employed to improve gastrointestinal dysfunction in patients with ulcerative colitis (UC) in China. SBS combined with mesalamine has been demonstrated to result in improve its curative effects without increasing any adverse reactions, but the underlying mechanism remains unclarified. Aim of the studyOur study aimed to illuminate the potential therapeutic effects and mechanisms of SBS, which is a medicine complementary to mesalamine, in the treatment of UC. Materials and methodsA prospective cohort study was conducted to evaluate the efficacy of SBS as a complementary medicine to mesalamine for patients with UC (n = 48). The patients in the control group (n = 24) were given mesalamine alone, whereas those in the experimental group were administered mesalamine combined with SBS. The therapeutic outcome was assessed at 8 weeks. The structures of the gut microbiota (GMB) were characterized by 16S rRNA sequencing, and the microbial tryptophan metabolites were analyzed by UPLC–MS/MS to investigate the mechanism through which SBS achieves its effects. ResultsOur results showed that the combination of SBS and mesalamine could significantly improve the clinical signs of UC by achieving mucosal healing and relieving colon damage. Interestingly, the combination of SBS and mesalamine could alter the GMB structures and increase the microbial levels of tryptophan metabolites, including indole-3-propionic acid and indole-3-acetic acid. ConclusionSBS combined with mesalamine is effective in improving the clinical and endoscopic outcomes of patients with UC. SBS, as a complementary therapy to conventional treatment, alleviates UC via the GMB-tryptophan metabolite axis.

OP25 Patients with moderate to severe Crohn’s Disease with and without prior biologic failure demonstrate improved endoscopic outcomes with risankizumab: Results from phase 3 induction and maintenance trials

Abstract Background Risankizumab (RZB), a selective interleukin-23 inhibitor, demonstrated clinically meaningful improvements in endoscopic outcomes in patients with moderate to severe Crohn’s disease (CD) during two phase 3 induction trials (ADVANCE and MOTIVATE) and the maintenance study (FORTIFY). Here, we compared the efficacy of RZB in inducing and maintaining improvements in endoscopic outcomes in patients with CD who demonstrated intolerance and/or inadequate response (IR) to biologic therapies (with prior bio-failure) versus those who demonstrated IR to conventional therapies only (without prior bio-failure). Methods Data included in this subgroup analysis included pooled data from patients randomized to receive intravenous (IV) RZB 600mg (N=527) or placebo (PBO) IV (N=362) every 4 weeks (wks) for 12wks during induction (ADVANCE+MOTIVATE), and data from patients receiving subcutaneous (SC) RZB 360mg (N=141) or withdrawn from RZB IV to receive PBO SC (withdrawal [PBO SC], N=164) every 8wks for 52-wks during maintenance. At Wks 12 and 52, endoscopic response, endoscopic remission, ulcer-free endoscopy (absence of ulceration), and deep remission (Wk52 only) were evaluated both in the overall population and in subpopulations of patients with and without prior bio-failure. (Endpoints are defined in Table footnotes). Safety was assessed throughout the studies. Results Approximately three-quarters of randomized patients included in this subgroup analysis had prior bio-failure (ADVANCE+MOTIVATE: 75.4%; FORTIFY: 73.8%). Higher rates of endoscopic response, endoscopic remission, and ulcer-free endoscopy were observed at Wk12 among patients receiving induction with RZB IV versus PBO IV. Subgroup analysis demonstrated treatment effects with risankizumab in patient subpopulations with and without prior bio-failure, with greater adjusted differences versus PBO in patients without prior bio-failure (Figure). At Wk52, endoscopic response, endoscopic remission, ulcer-free endoscopy, and deep remission rates favored RZB SC compared to withdrawal (PBO SC). Again, treatment effects were observed in patients with and without prior bio-failure, with greater adjusted differences versus withdrawal (PBO SC) in patients without prior bio-failure. RZB maintenance treatment was well-tolerated and no new safety signals were observed. The safety profile of RZB has been reported previously.1,2 Conclusion Induction and maintenance therapy with risankizumab achieved higher rates for endoscopic endpoints in patients with moderate to severe Crohn’s disease versus placebo, regardless of prior bio-failure status. However, numerically higher efficacy rates were observed in patients without prior bio-failure. 1 D’Haens, G. et al. in DDW 2021 2 Ferrante, M. et al. in UEGW 2021

DOP89 Infliximab and ustekinumab clearance during induction predicts post-induction endoscopic outcomes in patients with Crohn’s Disease

Abstract Background Monitoring of monoclonal antibody clearance has been hypothesised to be an appealing approach for predicting treatment outcomes in patients with inflammatory bowel diseases. We aimed to investigate the benefits of monitoring infliximab and ustekinumab clearance in patients with Crohn’s disease (CD) based on data from clinical trials. Methods Data were obtained from patients with moderate-to-severe CD starting infliximab (n=108)1 or ustekinumab (n=80)2 therapy. Endoscopic remission (CD Endoscopic Index of Severity &amp;lt;3) and endoscopic response (≥50% decrease from baseline in simple endoscopic score for CD) were assessed at week (w)12 and w24 of infliximab and ustekinumab therapy, respectively. A priori prediction (based on covariate data only; at w0) and a posteriori prediction (Bayesian forecasting using measured drug concentrations; during treatment) were performed using previously built population pharmacokinetic models (NONMEM 7.5).3,4 Covariates of fecal calprotectin, albumin, CD activity index, and antibodies towards infliximab (ATIs) were used to estimate infliximab clearance. Albumin and body weight were used to estimate ustekinumab clearance. Results Patients achieving endoscopic remission at w12 had significantly lower infliximab clearance and higher infliximab serum concentration at w2 and w6 of treatment (P &amp;lt;0.05, Table 1). Patients achieving endoscopic response at w24 had significantly lower ustekinumab clearance at w4 and w8, as well as a significantly larger reduction in clearance relative to w0 (P &amp;lt;0.05, Table 1). However, ustekinumab serum concentrations at w4 and w8 were similar between patients with and without endoscopic response (P &amp;gt;0.2, Table 1). Most patients with an early increase in infliximab clearance (16/22; 73%) and ustekinumab clearance (27/29; 93%) did not reach the endoscopic endpoint (P &amp;lt;0.05; Table 2). However, a decrease in clearance was no guarantee for endoscopic remission during infliximab therapy (false predictive rate 46%) and response during ustekinumab therapy (false predictive rate 69%). The infliximab clearance after start of induction therapy (at w2 and w6) was significantly higher in patients who developed ATIs during induction therapy (Figure 1). Conclusion Lower infliximab and ustekinumab clearance (absolute as well as relative to w0) early during induction predict more favourable endoscopic outcomes. In patients treated with ustekinumab, clearance monitoring may better predict endoscopic response at w24 as compared to standard therapeutic drug monitoring.

P347 Sarcopenia is a poor prognostic factor for endoscopic outcomes in patients with Crohn’s disease

Abstract Background Sarcopenia is defined as depletion in lean muscle mass with a loss of muscle strength and has been associated with increased morbidity and mortality in chronic diseases. Despite the risks and potential consequences of low lean muscle mass in patients with Crohn’s disease (CD), the impact of sarcopenia has been poorly evaluated. Therefore, the aim of our study was to assess the role of sarcopenia in predicting clinical and endoscopic outcomes in a cohort of CD patients. Methods Consecutive CD patients who started biologics between, 2015 and, 2020 and who underwent abdominal magnetic resonance imaging (MRI) within, 6 months from the beginning of the treatment were enrolled. Sarcopenia was defined as sex-specific total psoas area index (TPAI), measured at the, 3rd lumbar vertebra level, below the, 25th percentile. Multivariate analysis was used to evaluate whether sarcopenia could predict steroid-free clinical remission (Harvey-Bradshaw Index [HBI] &amp;lt;5 and no steroid treatment) and endoscopic response (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD ≤2 and Rutgeerts score i0-i1) after, 52 weeks of treatment. Results 358 patients were included. Sarcopenic patients were older (p = 0.001), with lower body mass index (BMI) (p = 0.001) and higher Charlson Comorbidity Index (p = 0.02). Furthermore, sarcopenia was associated with a lower rate of endoscopic response (p = 0.014) and a lower SES-CD and Rutgeerts score after, 52 weeks of treatment (p = 0.008; p = 0.001). In multivariate analysis, sarcopenia was an independent predictor of absence of endoscopic response (odds ratio [OR] = 2.8;, 95% confidence interval (95% CI), 1.1–7.5; p = 0.02), along with smoking (OR = 2.39;, 95% CI, 1.05–5.44; p = 0.038) and perianal disease (OR = 2.69;, 95% CI, 1.19–6.08; p = 0.017). Sarcopenia was not associated with steroid-free clinical remission. Conclusion This is the first study demonstrating that sarcopenia is a poor prognostic factor for endoscopic response in CD patients. These results suggest that, in the future, screening for sarcopenia on routine abdominal MRI could be used in clinical practice for better management of CD patients in need of biological therapy. Further studies with a larger sample size and a validation cohort are needed to confirm our data.

DOP84 Risankizumab maintenance therapy results in sustained improvements in endoscopic outcomes in patients with moderate to severe Crohn’s Disease: Post-hoc analysis from the phase 3 study FORTIFY

Abstract Background Data from Phase 3 studies in Crohn’s disease (CD) demonstrated significant improvements in endoscopic outcomes with risankizumab (RZB) versus placebo (PBO) following 12-weeks (wks) induction therapy. Continued maintenance therapy with 360mg RZB SC led to significantly higher rates of endoscopic response and remission at Wk52 compared to withdrawal/placebo. This post-hoc analysis examined the durability of SC RZB maintenance therapy for endoscopic outcomes among patients achieving these endpoints at the end of induction Methods Patients achieving clinical response with 12-wks IV RZB induction therapy in ADVANCE or MOTIVATE entered the maintenance study, FORTIFY, and received either RZB SC or had RZB withdrawn and received placebo for 52 wks. For this analysis, endoscopic outcomes in the RZB 360 mg SC (N=141) and withdrawal/placebo (N=164) arms are reported. Maintenance of endoscopic response, endoscopic remission, and/or an SES-CD score of 0–2 were assessed at Wk52 in patients who achieved these endpoints at Wk0 of maintenance (Wk12 of induction). Safety was assessed throughout the study. Results Following 12-wks of IV RZB induction therapy (FORTIFY Wk0), 141 patients were randomized to RZB 360 mg (patients achieving endoscopic response, 55/141; endoscopic remission, 39/141; SES-CD score of 0–2, 29/141) and 164 were randomized to withdrawal (PBO SC) (patients achieving endoscopic response, 73/164; endoscopic remission, 46/164; SES-CD 0–2, 32/164). Maintenance of endoscopic response at Wk52 was demonstrated in 70.2% (39/55) of patients receiving RZB 360 mg SC versus 38.4% (28/73) of patients in the withdrawal (PBO SC) arm (P&amp;lt;0.001). Maintenance of endoscopic remission at Wk52 was demonstrated in 74.4% (29/39) of patients receiving RZB 360 mg versus 23.9% (11/46) of patients in the withdrawal (PBO SC) arm (P&amp;lt;0.001). Maintenance of an SES-CD score from 0–2 at Wk52 was demonstrated in 65.5% (19/29) of patients receiving RZB 360 mg versus 21.9% (7/32) of patients in the withdrawal (PBO SC) arm (P&amp;lt;0.001).RZB maintenance treatment was well-tolerated and no new safety signals were observed. The safety profile of RZB has been reported previously.1–5 Conclusion RZB IV induction followed by SC maintenance therapy led to sustained improvements in endoscopic outcomes, demonstrating the durability of efficacy with continued RZB treatment in patients with moderate to severe CD. Reference 1. Feagan, B. G. et al. Lancet 389, 1699–1709 (2017) 2 Feagan, B. G. et al. Lancet Gastroenterol Hepatol 3, 671–680 (2018) 3 Ferrante, M. et al. Journal of Crohn’s and Colitis jjab093 (2021) 4 Ferrante, M. et al. in UEGW 2021 5 D’Haens, G. et al. in DDW 2021

Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn\u2019s disease: a Chinese real-world study

BackgroundUstekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting.MethodsWe retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis.ResultsNineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02).ConclusionsUST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation.Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

P307 Modelling of the relationship between ustekinumab exposure, faecal calprotectin and endoscopic outcomes in patients with Crohn’s disease

Abstract Background In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn’s disease (CD) on ustekinumab achieved endoscopic response and 10.9% achieved endoscopic remission at week (w)44. We aimed to investigate if improved endoscopic outcomes can be achieved through dose optimisation based on a population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis. Methods Real-world data were obtained from 83 patients with moderate-to-severe CD (94% multi-refractory) enrolled in a prospective cohort study receiving ustekinumab 6 mg/kg induction and every eight-week (q8w) 90 mg maintenance therapy. Ustekinumab serum concentrations were measured at mid-dose (w4) and trough (w8, w16, w24). Faecal calprotectin (fCal) was measured at baseline and at w4, w8, w16, w24. Endoscopic response (≥50% decrease in simple endoscopic score for CD [SES-CD]) and endoscopic remission (SES-CD ≤2) were assessed at w24. Modelling and simulation were performed using NONMEM 7.4. Results Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fCal, and a logistic regression popPD model linking fCal at w8 to endoscopic outcomes at w24 (Figure 1). Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. The terminal half-life of ustekinumab in a median patient (bodyweight 65 kg, serum albumin 42.7 g/L) was 20.4 days. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1,800 μg/g to 694 μg/g (Figure 2a) The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1,800 μg/g to 214 μg/g (Figure 2b).The results from the simulation-based comparison of q8w and q4w maintenance dosing are shown in Table 1. Dose doubling (180 mg q8w), as opposed to interval halving (90 mg q4w), was predicted to result in a ustekinumab trough concentration of 2.4 μg/mL instead of 4.8 μg/mL. Conclusion The developed model can guide clinical trial design and support model-informed dose optimisation to improve endoscopic outcome rates. Although our analyses showed that q4w dosing resulted in higher ustekinumab and lower fCal concentrations, the proportion of patients achieving endoscopic remission was limited.