Simple Endoscopic Score For Crohn's Disease Research Articles

Assessment of Treatment Response in Known Crohn's Disease-A Prospective Blinded Study Comparing the Diagnostic Accuracy of Intestinal Ultrasound, Magnetic Resonance Enterocolonography, Panenteric Capsule Endoscopy, and Fecal Calprotectin.

Minimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn's disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD. This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn's Disease (SES-CD) with IC defined treatment response. Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn's Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively. IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.

Gut Microbial Signatures in Pediatric Crohn's Disease Vary According to Disease Activity Measures and Are Influenced by Proxies of Gastrointestinal Transit Time: An ImageKids Study.

We investigated relationships between disease activity measures and the gut microbiome in children with Crohn's disease (CD) and how these were confounded by gastrointestinal transit time. Microbiome was profiled (16S rRNA sequencing) in feces from 196 children with CD. Sixty participants also provided samples after 18 months. Mural inflammation (Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index, PICMI), the simple endoscopic score for CD, and the weighted pediatric Crohn's disease activity index (wPCDAI) were assessed. Fecal calprotectin, plasma C-reactive protein (CRP), and fecal water content (FWC), a proxy of gastrointestinal transit time, were measured too. Microbiome α diversity, clustering, and differential taxa were related to disease status, but varied remarkably by disease activity measure used. The strongest relationships between microbiome and disease activity status were observed using wPCDAI; fewer or no relationships were seen using more objective measures like PICMI. Taxa predictive of disease activity status were dependent on the disease activity measure used with negligible overlap. Active disease was associated with more pathobionts (eg, Viellonella, Enterobacterales) and fewer fiber-fermenting organisms. The effect FWC had on microbiome superseded the effect of active disease for all disease activity measures, particularly with wPCDAI. Accounting for FWC, the differences in microbial signatures explained by disease activity status were attenuated or lost. In CD, microbiome signatures fluctuate depending on the measure used to assess disease severity; several of these signals might be secondary disease effects linked with changes in gut motility in active disease. PICMI appears to be less influenced when studying relationships between microbiome and mural inflammation in CD.

Does HLA-DQA1*05 carriage have a greater impact on the outcome of infliximab therapy for isolated small-bowel Crohn's disease?

Carriage of HLA-DQA1*05 is thought to increase the formation of anti-tumour necrosis factor alpha (TNF-α) antibodies, reducing the drug efficacy in Crohn's disease (CD) patients. However, little data are currently available for small-bowel Crohn's disease (SB-CD). A specific assessment of the impact of HLA-DQA1*05 on the clinical response to treatment with infliximab (IFX), a TNF-α antagonists, in SB-CD patients is necessary. We conducted a single-center retrospective study that included 106 SB-CD patients treated with IFX. The serum samples were collected for antibodies to infliximab (ATI) testing and HLA-DQA1*05 genotyping. Double-balloon enteroscopy (DBE) was performed following the IFX treatment, with endoscopic outcomes evaluated using the partial simple endoscopic score for CD (pSES-CD), whereas the clinical response was assessed with the Crohn's disease activity index (CDAI). Multivariate logistic regression and multivariate COX regression analyses were employed to analyze the correlation of the HLA-DQA1*05 genotypes with other clinical variables. In this study, 30.2% of SB-CD patients carried the HLA-DQA1*05 allele, which significantly increased their risk of ATI generation (odds ratio [OR]=2.337, p=.043), but it was not associated with the clinical response to IFX and drug persistence (OR=2.356, p=.145; OR=0.457, p=.249). The endoscopic remission rates were 40.6% (13/32) and 55.4% (41/74) in HLA-DQA1*05 carriers and non-carriers, respectively. HLA-DQA1*05 was not associated with endoscopic remission (OR=0.684, p=.414). The HLA-DQA1*05 variant is identified as a significant risk factor of ATI formation in Chinese patients with SB-CD, but is not associated with the clinical response of IFX treatment and endoscopic remission of SB lesions.

Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.

Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD. Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm. Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively. Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.

Performance of bowel preparation quality scales in patients with Crohn's disease.

The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. To evaluate the operating properties of instruments used to assess BP quality in patients with CD. We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100-mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES-CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within-patient correlation between instruments and the visual analogue scale using mixed-effect models. The correlation between BP quality and SES-SD scores was assessed using Spearman's rho. Inter- and intra-rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter-rater reliability ICC ≥0.41). The visual analogue scale had substantial inter- and almost perfect (ICC ≥0.81) intra-rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD.

Changes in endoscopic activity and classification of lesions with panenteric capsule endoscopy in patients treated for Crohn's disease - a prospective blinded comparison with ileocolonoscopy, faecal calprotectin and C-reactive protein.

Panenteric capsule endoscopy (PCE) is a minimally invasive modality that may replace ileocolonoscopy (IC) in selected patients with Crohn's disease (CD). This study aimed to evaluate the dynamics of repeated assessment with PCE in patients receiving medical treatment for ileocolonic CD. This prospective, blinded, multicentre study included patients with endoscopically active CD. Patients were scheduled for IC, PCE, faecal calprotectin and C-reactive protein before and 12 weeks after treatment with corticosteroids or biological therapy. The endoscopic disease activity was assessed with the Simple Endoscopic Score for Crohn's Disease (SES-CD). 31 patients entered the study, and PCE visualized 148 (95.5%) and 128 (82.6%) ileocolonic bowel segments before and after medical treatment, respectively. The median SES-CD decreased from 14 (IQR 8-17) to 5 (IQR 0-14) (P < 0.001) and 14 (IQR 10-17) to 6 (IQR 3-12) (P < 0.001) with IC and PCE, respectively. The repeated measurement correlation between PCE and IC was very strong (r = 0.77, P < 0.001), strong compared to faecal calprotectin (r = 0.42, P = 0.003) and moderate compared to C-reactive protein (r = 0.36, P = 0.005). The mean score for ulcer size, ulcerated surface and affected surface was equal to that of IC before and after treatment. PCE had a sensitivity and specificity of 80.6% (CI 62.5-92.5) and 93.8% (CI 79.2-99.2) for ulcer healing compared to IC. PCE is responsive in patients treated for CD and may serve as a minimally invasive alternative to IC in selected patients.

Mirikizumab Sustained Impact on Fatigue in Patients with Moderately to Severely Active Crohn's Disease in the Phase 2 AMAG Study.

Fatigue is a burdensome,under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104). Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200mg, 600mg, or 1000mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000mg) and PBO patients (PBO/1000mg) who received 1000mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient. At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers. Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.

Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4+ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4+ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4+ T cells of UC patients compared with that in Crohn’s disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn’s Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn’s disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4+ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4+ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4+ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4+ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.

Re-evaluating Methods for Assessing Differences in Response in Ileal vs. Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease (CD). We aimed to determine whether disease location affects response to filgotinib, a Janus kinase (JAK) inhibitor, in patients with moderate-to-severely active Crohn's disease (CD) and applying appropriate methods to account for differences in measuring disease activity in the ileum compared to the colon. This post-hoc analysis of data from the FITZROY phase 2 trial (NCT02048618) compared changes in the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD) amongst patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200mg daily or placebo. A mixed effects model for repeated measures was used to test whether ileal disease responded differently than colonic disease, by evaluating for effect modification using the interaction term of treatment assignment-by-disease location. Numerically greater proportions of patients with isolated colonic disease compared to ileal-dominant CD achieved clinical remission (CDAI <150, 75.9% vs. 41.6%) and endoscopic response (SES-CD reduction by 50%, 52.5% vs. 15.5%) at Week 10. However, after adjusting for baseline disease activity by disease location and within-patient clustering effects, there was no significant difference in treatment response by disease location (mean difference in ΔCDAI between ileal-dominant vs. isolated colonic disease +9.24 [95% CI: -87.19, +105.67], p=0.85; mean difference in ΔSES-CD -1.93 [95% CI: -7.03, +3.44], p=0.48). Filgotinib demonstrated similar efficacy in ileal-dominant and isolated colonic CD when controlling for baseline disease activity and clustering effects.

Mucosal Healing with Vedolizumab in Patients with Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND & AIMSVedolizumab is indicated for the treatment of chronic pouchitis in the EU. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements. METHODSEARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis. Centrally read endoscopic and histological evaluation was performed at baseline, week (W)14, and W34. Ulcer count, adapted Simple Endoscopic Score for Crohn’s Disease (SES-CD) in the pouch, and Pouchitis Disease Activity Index (PDAI) histological component were evaluated. PDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at W14 and W34 were compared by MH status at W14. RESULTSFollowing treatment, mean (SD) number of ulcers in vedolizumab-treated patients reduced from 15.1 (16.4) to 5.0 (4.9) at W14 and 2.7 (3.2) at W34 vs placebo-treated patients with corresponding values of 11.8 (11.3), 13.4 (18.4), and 9.7 (13.8) (vedolizumab vs placebo difference [95% CI]: W14:−8.4 [−14.3,−2.6]; W34:−7.0 [−12.0,−2.0]). More patients receiving vedolizumab vs placebo achieved reduction in ulcerated pouch surface area (W14: 52.4% vs 20.0%; difference 32.4p.p [9.7, 51.4]; W34: 52.1% vs 12.9%; difference 40.2p.p [15.6, 60.3]), absence of ulceration (W14: 23.8% vs 7.5%; difference 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference 18.8p.p [-2.0, 39.5]), SES-CD remission (W14: 23.8% vs 7.5%; difference 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference 18.8p.p [-2.0, 39.5]) and MH (W14: 16.7% vs 2.5%; difference 14.2p.p [1.9, 26.4]). Patients with MH at W14 had higher rates of PDAI and IBDQ remission at W14 and W34 than those without. CONCLUSIONVedolizumab induced endoscopic improvements in patients with chronic pouchitis, which was associated with improved outcomes at W34, particularly in patients achieving MH at W14. ClinicalTrials.gov number, NCT02790138.

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn’s disease patients over three years

Long-term data on ustekinumab in real-life Crohn’s disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn’s disease patient cohort with a three-year follow-up. Crohn’s disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn’s Disease (SES-CD)) were collected for three-years’ time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn’s disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn’s disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

Value of different endoscopic scoring methods in assessing disease activity in pediatric Crohn's disease

To explore the value of different endoscopic scoring methods in assessing disease activity in pediatric Crohn's disease (CD). A total of 70 children diagnosed with CD at the Children's Hospital of Chongqing Medical University from January 2018 to January 2023 were included. Clinical disease activity was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), while different endoscopic scores were assigned based on endoscopic findings. Spearman rank correlation analysis was used to evaluate the correlation between each endoscopic scoring method and PCDAI as well as laboratory indicators. Kappa test was used to assess the consistency between colonoscopy/capsule endoscopy scoring methods and PCDAI in determining CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of laboratory indicators in predicting endoscopic activity. The PCDAI score showed a moderate positive correlation with the scores of Crohn's Disease Endoscopic Index of Severity (CDEIS) (rs=0.696, P<0.01), Simple Endoscopic Score for Crohn's Disease (SES-CD) (rs=0.680, P<0.01), Lewis Score (rs=0.540, P<0.01), and Capsule Endoscopy-Crohn's Disease Index (CE-CD) (rs=0.502, P<0.01). The consistency between all endoscopic scoring methods and PCDAI in determining CD activity was poor (Kappa=0.069-0.226). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hematocrit (HCT), and serum albumin (ALB) levels showed a moderate correlation with the PCDAI score and the scores of colonoscopy scoring methods (CDEIS and SES-CD) (|rs|=0.581-0.725, P<0.01), but a weak correlation with the scores of capsule scoring methods (P<0.05). ESR and CRP had higher area under the curve (AUC) values in predicting disease activity based on PCDAI, CDEIS, SES-CD, and Lewis Score compared to HCT and ALB (P<0.05). CDEIS, SES-CD, Lewis Score, and CE-CD can be used to evaluate disease activity in pediatric CD, but they do not fully correspond with disease activity assessed by PCDAI. Elevated levels of ESR and CRP can predict clinical and endoscopic disease activity in children with CD.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

P1040 Comparative effectiveness of upadacitinib versus ustekinumab in patients with moderately to severely active Crohn’s disease: a matching-adjusted indirect comparison

Abstract Background Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL 12/23 antagonist, are effective treatments for moderately to severely active Crohn’s Disease (CD). In the absence of head-to-head data, a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) was conducted to indirectly compare efficacy of UPA vs UST. Methods Individual patient (pt)-level data from phase 3 UPA trials and published data from phase 3 UST trials were used. For induction, pts received UPA 45mg daily or PBO for 12 weeks or UST ~6mg/kg IV or PBO IV at week 0 with 8-week follow-up. For maintenance, UPA clinical responders were re-randomized to UPA 15mg, 30mg, or PBO daily for 52 weeks. UST clinical responders were re-randomized to 90mg SC (every 8 or 12 weeks) or PBO SC for 44 weeks. UPA pts had baseline (BL) CD Activity Index (CDAI) 220-450; those with prior UST or vedolizumab exposure were excluded. Treatment effect modifiers, including BL mean CDAI, Simple Endoscopic Score for CD (SES-CD), median C-reactive protein, prior biologic(s) failure, and disease location, from UPA data were weighted to match the UST population. Outcomes assessed were CDAI response (≥100-point decrease or CDAI &amp;lt;150), CDAI remission (CDAI &amp;lt;150), endoscopic response (SES-CD ≥50% decrease), and SES-CD ≤2. Separate MAICs were conducted for induction and maintenance; data reported for induction clinical outcomes are stratified by prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR). Results A greater proportion of UPA- vs UST-treated pts achieved endoscopic response (difference 26.3%, P&amp;lt;0.001) and SES-CD ≤2 (difference 9.9%, P&amp;lt;0.05) at the end of induction. In TNF-IR patients, a greater proportion of UPA- vs UST-treated pts achieved CDAI response at the end of induction (difference 18.2%, P&amp;lt;0.05) and at the end of Week 8 (difference 26.0%, P&amp;lt;0.001). CDAI remission rates were also higher at end of Week 8 for UPA- vs UST-treated pts (difference 13.3%, P&amp;lt;0.05). Rates of achieving CDAI response and remission were similar between UPA- and UST-treated pts at the end of induction and Week 8 among bio-naïve pts. Following maintenance treatment, similar rates of SES-CD ≤2, endoscopic response, and CDAI remission were obtained in the total population of UPA and UST-treated pts. Conclusion Pts with moderately to severely active CD treated with UPA achieved higher rates of endoscopic (total population) and clinical (TNFi-IR population) outcomes during induction compared to UST-treated pts. Outcomes at the end of maintenance were similar for UPA and UST, however, results should be interpreted with caution due to low sample size.

P741 Characterisation of endoscopic improvements with risankizumab treatment in patients with moderately to severely active Crohn’s disease

Abstract Background Endoscopy is used to objectively evaluate disease severity in patients with Crohn’s disease (CD), and endoscopic remission is a target for disease control. Ulcer size is associated with longer-term endoscopic remission, so evaluating ulcers may inform longer-term outcomes. Risankizumab (RZB) is an interleukin 23p19 inhibitor approved for adults with moderately to severely active CD. In phase 3 trials, greater proportions of patients with CD achieved endoscopic outcomes including ulcer-free endoscopy with RZB induction and maintenance therapy vs placebo (PBO).1,2 We further investigated the effect of RZB on endoscopic outcomes by evaluating improvements in Simple Endoscopic Score for CD (SES-CD) components during these phase 3 trials. Methods This post hoc analysis used data from the phase 3 induction studies (ADVANCE [NCT03105128] and MOTIVATE [NCT03104413]) and phase 3 maintenance study (FORTIFY [NCT03105102]). Patients received intravenous (IV) doses of RZB (600 mg or 1200 mg) or PBO for 12 weeks, and clinical responders to IV RZB received RZB maintenance therapy (180 mg or 360 mg subcutaneously [SC]) or PBO (withdrawal) for 52 weeks. This analysis evaluated change in SES-CD subscores (size of ulcers, affected surface, and ulcerated surface) at induction week 12 and maintenance week 52 across ileocolonic segments (rectum, left colon, transverse colon, right colon, and ileum); analyses of improvement were based on a nonresponder imputation for patients with baseline subscores &amp;gt; 0 in the specific ileocolonic segment. Data from the induction studies were pooled for analysis; results for RZB 1200 mg IV induction are not reported. Shift data were from patients with available values. Results During the induction and maintenance studies, a numerically greater proportion of patients treated with RZB compared with PBO experienced improvements in any ileocolonic segment in SES-CD size of ulcers, ulcerated surface, and affected surface subscores (Figure). In general across each segment, a numerically greater proportion of patients treated with RZB induction and maintenance therapy compared with PBO experienced improvement from baseline SES-CD size of ulcer subscores of 2 or 3 (diameter 0.5–2 cm or diameter &amp;gt; 2 cm, respectively) to subscores of 0 or 1 (none or diameter 0.1–0.5 cm, respectively) at weeks 12 and 52 (Table). Similar patterns were observed for SES-CD ulcerated surface and affected surface subscores. Safety data for the phase 3 studies have been reported previously. Conclusion Patients treated with RZB experienced greater improvements in SES-CD components compared with PBO during the induction and maintenance studies.

P368 Correlation between patient-reported outcome measures in inflammatory bowel disease and other measures of disease activity: a systematic review

Abstract Background The clinical activity of inflammatory bowel disease (IBD) has traditionally been evaluated by healthcare professionals. To allow direct reporting of symptoms by patients, several patient-reported outcome measures (PROMs) have been developed. We evaluated the correlation between IBD-specific PROMs and measures of endoscopic activity. Methods A systematic review of the literature was performed up to June 2022. Searches were conducted in three databases (PubMed, Scopus and Web of Science). The search protocol was registered in PROSPERO (CRD42022383899). Studies reporting the correlation between self-administered, IBD-specific PROMs and endoscopic scores were included. A descriptive analysis was performed by assessing the correlation between PROMs and IBD endoscopic activity. PROMs used in Crohn’s disease (CD) and ulcerative colitis (UC) were considered separately. Results Seventeen PROMs were identified encompassing a series of IBD signs and symptoms, mainly abdominal pain (n=10), stool frequency (n=6) and rectal bleeding (n=4). Twenty-two studies assessed correlations of PROMs with existing clinical measures of disease activity and/or their accuracy in predicting remission. The mainly used endoscopic indices were Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore (MES) (n=11), and clinical indices were Harvey–Bradshaw Index for CD (n=7) and SCCAI for UC (n=7). Most studies used more than one comparator as standard for validation. A marked heterogeneity in the study design and statistical methods was observed. In CD, five studies analysed correlations between PROMs and SES-CD. They generally found weak correlations with PROMs (PRO2, n=2; mobile Health Index [mHI]-CD, n=1) (Figure), except for one which found a negative moderate correlation between PRO2 and SES-CD. The strongest correlation was with the stool frequency item of the Monitor IBD at home (MIAH) questionnaire. In UC, four studies assessed the correlation between PROMs and MES. Positive weak-to-moderate correlations were found with PRO2, MIAH rectal bleeding item and mHI-UC MES in four studies. Conclusion In CD, PROMs poorly correlate with endoscopic activity. However, in UC, rectal bleeding reasonably correlates with endoscopic status. It is well known that IBD symptoms overlap with those of other digestive diseases as functional disorders, especially in CD. In line with this, our data suggest that PROMs cannot substitute endoscopic data to monitor disease activity in IBD, especially in CD patients. Nonetheless, they represent a valuable complementary instrument to comprehensively describe disease control by capturing patient perspective. More studies are needed to better evaluate correlations between PROMs and clinical disease activity measures.

P983 Treatment of patients with moderate-to-severe Crohn’s disease with subcutaneous infliximab leads to an endoscopic response across all segments of the colon and terminal ileum: A post hoc analysis of the LIBERTY-CD study

Abstract Background Mucosal healing (MH) has been associated with positive long-term clinical and surgical outcomes in patients (pts) with Crohn’s disease (CD).1 Patterns of MH vary by therapeutic agent, with limited efficacy in the terminal ileum.2–4 This post hoc analysis aimed to investigate the pattern of endoscopic MH across intestinal segments in pts who received subcutaneous (SC) infliximab (IFX) maintenance treatment in the Phase 3 LIBERTY-CD study. Methods LIBERTY-CD demonstrated superior efficacy of SC CT-P13 120 mg every 2 weeks (Q2W) vs placebo (PBO) after IV IFX induction for clinical remission and endoscopic response at Week (W) 54.5 This post hoc analysis evaluated centrally read and batch analysed Simple Endoscopic Score for Crohn's Disease (SES-CD) values obtained at screening, W22 and W54 for 5 ileocolonic segments (rectum; left, transverse and right colon; and terminal ileum). Pts with missing data or who underwent dose escalation to SC IFX 240 mg Q2W upon loss of response from W22 were imputed as non-responders. Endoscopic complete MH (CMH; defined as SES-CD=0) or partial MH (PMH; defined as ≥50% decrease in the SES-CD from screening) were evaluated for segments that had endoscopic abnormalities at screening (segmental SES-CD ≥1 at screening). Results were analysed descriptively. Results Among all randomised pts (N=343; SC CT-P13: n=231, PBO: n=112), the most frequently affected segment at screening was the left colon (187/343; 54.5%), followed by the right colon (185/343; 53.9%), rectum (163/343; 47.5%), terminal ileum (156/343; 45.5%) and transverse colon (134/343; 39.1%). In an analysis of all affected segments, endoscopic CMH rates were higher with SC CT-P13 vs PBO (Figure 1A). Endoscopic CMH rates in the terminal ileum at W54 were 46.7% and 19.6% in the SC CT-P13 and PBO arm, respectively (p=0.0014). PMH rates were also significantly higher in the SC CT-P13 arm across all segments at W22 and W54 (Figure 1B), with rates in the terminal ileum of 64.8% and 33.3% in the SC CT-P13 and PBO arm, respectively (p=0.0003). Conclusion SC IFX 120 mg Q2W led to high and consistent endoscopic MH rates across all segments, including the terminal ileum. Early observation of endoscopic MH (at W22) underscores the potency of SC IFX treatment. Further studies are warranted to investigate the association between segmental MH and long-term outcomes. 1Otte ML et al. World J Gastroenterol 2023;29:1157–72. 2Danese S et al. Gastroenterology 2019;157:1007–18. 3Reinisch W et al. J Crohns Colitis 2017;11:425–34. 4Wu Y et al. Therap Adv Gastroenterol 2020;13:1756284820976923. 5Hanauer SB et al. Gastroenterology 2023;164(S6):S220–1.

OP09 Oral ritlecitinib and brepocitinib in patients with moderate to severe active Crohn’s Disease: Data from the PIZZICATO umbrella study

Abstract Background Oral ritlecitinib (RIT; JAK3/TEC family kinase inhibitor) and brepocitinib (BRE; TYK2/JAK1 inhibitor) are being assessed in a 64-week (wk) phase 2a randomised, double-blind, induction-maintenance, umbrella study (PIZZICATO; NCT02958865) in participants (pts) with moderate-to-severe active Crohn’s disease (CD) with inadequate, loss of response or intolerance of corticosteroids, immunosuppressants or biologics. We report the efficacy and safety results from the 12-wk induction period. Methods Pts 18-75 years old with endoscopic confirmation of active CD with Simple Endoscopic Score for CD (SES-CD) ≥7/≥4 for isolated ileal disease, and average daily liquid/soft stool frequency (SF) ≥2.5 or daily abdominal pain (AP) ≥2.0 were included. Pts were randomised to RIT 200 mg once daily (QD) for 8 wks then 50 mg QD for 4 wks and matching placebo (PBO) in a 2:1 ratio or BRE 60 mg QD for 12 wks and matching PBO in a 2:1 ratio. Pts continued in their respective arms with open-label RIT 50 mg or BRE 30 mg QD for 52 wks. PBO arms were combined for analysis. Pts achieving SES-CD 50 (≥50% reduction in SES-CD from baseline [BL]; primary endpoint Wk 12), Clinical Disease Activity Index (CDAI) remission (CDAI&amp;lt;150) and CDAI-100 response for pts with BL CDAI≥220, clinical response (≥30% reduction from BL in AP or SF; neither worse than BL) and remission (SF≤1.5 and AP≤1; neither worse than BL) were assessed. Safety was also evaluated. Results A total of 244 pts were randomised and received treatment in the induction period with BL mean age of 34.6-36.5 years, median SES-CD 11-14, and prior biologics experience 69-76% across groups. The proportion of pts achieving SES-CD 50 was significantly higher at Wk 12 with RIT 200/50 mg QD and BRE 60 mg vs PBO (change from PBO: RIT 14.3% [90% CI, 4.0, 24.5], BRE 21.4% [10.0, 32.9]; Table). Statistical significance vs PBO was observed for RIT at Wks 8 and 12 and BRE at Wk 12 for CDAI remission, CDAI-100, clinical response and remission by SF or AP. Most treatment emergent adverse events (TEAEs) in both groups were mild or moderate. Herpes infections occurred in 1 pt in each group and serious infections in 1 pt in RIT and 2 in BRE. No deaths or malignancies occurred. No events of thromboembolism or MACE occurred for RIT. One pt on BRE had a TEAE of pulmonary embolism. There were no clinically significant observations for labs. Conclusion Both RIT and BRE met the primary endpoint in the induction period with significant clinical improvement vs PBO in pts with active CD. Other meaningful efficacy endpoints had similar results to the primary endpoint for both therapies. RIT and BRE had an acceptable safety and tolerability profile that was consistent with previous studies.

P1074 Impact of body mass index (BMI) on clinical outcomes and drug levels in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study

Abstract Background Obesity and high levels of visceral adipose tissue are associated with lower response rates to intravenous (IV) infliximab (IFX).1 Subcutaneous (SC) IFX is a novel formulation that demonstrated superiority to placebo as maintenance therapy in patients (pts) with moderate-to-severe active Crohn’s disease (CD) in the Phase 3 LIBERTY-CD study. Assessing efficacy of SC IFX by BMI is important as, unlike the IV formulation, pts receive a fixed dose. This post hoc analysis aimed to assess the association between BMI and the efficacy of SC IFX therapy. Methods Data from LIBERTY-CD (NCT03945019) were analysed; 231 pts from the SC IFX arm were divided into four subsets by their BMI: underweight (BMI &amp;lt;18.5 kg/m2, n=27); normal (18.5–24.9 kg/m2, n=133); overweight (25–29.9 kg/m2, n=53); obese (≥30 kg/m2, n=18). Co-primary endpoints at Week (W) 54 (clinical remission [CD Activity Index (CDAI) score &amp;lt;150]; endoscopic response [≥50% decrease in Simple Endoscopic Score for CD (SES-CD) from baseline (BL)]) and W54 change from BL in CDAI score were assessed by BMI subset. Correlations between BMI and CDAI score, SES-CD or median trough level of infliximab (TLI), and the impact of BMI on W54 TLI, were evaluated. Analyses were conducted in a descriptive manner. Results At W54, there were no statistically significant differences in co-primary endpoints or change from BL in CDAI score across BMI subsets, despite descending trends in rates of achieving co-primary endpoints, change in CDAI score and TLI with increasing BMI (Table). From the underweight to obese subsets, clinical remission rates were 63.0%, 66.2%, 58.5% and 44.4% (p=0.125), endoscopic response rates were 55.6%, 36.1%, 41.5% and 27.8% (p=0.207) and median changes from BL in CDAI score were −227.3, −212.9, −196.2 and −204.5 (p=0.358). No significant correlations were observed between BMI and CDAI score (Pearson r=0.0972/p=0.141; Spearman rank r=0.0619/p=0.349) or BMI and SES-CD (Pearson r=0.0446/p=0.507; Spearman rank r=0.0375/p=0.577), while there was a weak, but significant, negative correlation between BMI and TLI (Pearson r=−0.2808/p&amp;lt;0.001; Spearman rank r=−0.2829/p&amp;lt;0.001) (Figure). Additionally, there was a significant difference in median W54 TLI across BMI subsets from underweight to obese (17.0, 13.6, 9.3 and 6.6 µg/mL; p=0.007) (Table). Conclusion While there was a significant difference in TLI across BMI subsets, there was no statistically significant impact of BMI on W54 clinical or endoscopic outcomes. These results could be explained by the relatively high TLI achieved with the SC formulation. Further larger and longer-term studies including pts with morbid obesity and utilising body composition assessment are warranted. 1Yarur A et al. Gastroenterology 2023;165:963–75.

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 &amp;gt;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&amp;lt;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&amp;lt;0.0001), mucosal healing (wk24: 25.1% vs 14.4%, P&amp;lt;0.01; wk48: 30.2% vs 12.1%, P&amp;lt;0.0001), and the composite endpoint of deep remission (wk24: 22.0% vs 10.2%, P&amp;lt; 0.001; wk48: 22.7% vs 10.9%, P&amp;lt;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