Abstract Background The ability to predict failure of infliximab (IFX) in acute severe ulcerative colitis (ASUC) is crucial to identify patients who may benefit from dose-escalation, sequential rescue or early colectomy. Methods PREDICT-UC (NCT02770040) was a randomised controlled trial that compared IFX dosing strategies in ASUC.1 Clinical factors and biomarkers were collected daily between day 0 to 3 post-IFX and assessed on their ability to predict IFX failure (Lichtiger score ≥10 on day 14) and 3-month colectomy. Stepwise logistic regression was used to develop a Risk of IFX Failure (RIF) index, which was calibrated against the observed risk of IFX failure. The RIF index represents the predicted probability of IFX failure and takes on values between 0 and 1. Internal validation was performed using bootstrap validation. Results Of 138 patients, 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg; 39 (28%) experienced IFX failure and 17 (12%) required colectomy by 3 months. There was no difference in lymphocyte count (LC, ×109/L) on day 0 (prior to IFX) in patients who failed or responded to IFX (median [IQR] 1.1 [0.9–1.6] vs 1.3 [0.9–1.8], P=0.47). LC rose by day 3 in both groups, though to a lesser degree in patients who failed IFX (median [IQR] 1.9 [1.4–2.8]) compared to responders (3.3 [2.1–4.9]; P=0.004), and lower in patients requiring colectomy (median [IQR] 1.4 [1.1–1.9] vs 3.0 [2.0–4.8]; P<0.001). A lower day 3 LC was predictive of IFX failure (AUC 0.71, 95% CI 0.60–0.81) and colectomy (AUC 0.83, 95% CI 0.74–0.92). A higher CRP was predictive of both IFX failure and colectomy at all time-points from days 0 to 3 (day 3 CRP AUC 0.68, P=0.003 and 0.70, P=0.019 respectively). A lower day 3 albumin predicted IFX failure (AUC 0.63, P=0.039) while a lower day 2 albumin predicted colectomy (AUC 0.66, P=0.042). The final RIF index comprised day 3 stool frequency, rectal bleeding score, CRP and LC. The RIF index had a naïve AUC of 0.80 and an optimism-adjusted AUC of 0.73 (95% CI 0.65–0.80) for predicting IFX failure, and a naïve AUC of 0.90 and an optimism-adjusted AUC of 0.88 (95% CI 0.81–0.94) for predicting colectomy. A RIF index threshold of ≥0.15 had an 85% sensitivity and 90% negative predictive value (NPV) for IFX failure and a 94% sensitivity and 98% NPV for colectomy, while a threshold of ≥0.50 had a 92% specificity and 69% positive predictive value (PPV) for IFX failure, and an 88% specificity and 42% PPV for colectomy. Conclusion Lymphocytosis by day 3 is a novel predictor of response to IFX rescue in ASUC. The RIF index is a simple on-treatment risk index that predicts IFX failure and colectomy, and may be used to inform IFX dose-optimisation or switch to alternate therapies. References 1Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.

Abstract Background Information on infectious complications following acute severe ulcerative colitis (ASUC) is limited. The aim of this study was to determine rates of infections following ASUC treatment and the associated risk factors, using data from the Asian Organization for Crohn’s and Colitis (AOCC) and the Australia New Zealand IBD Consortium (ANZIBDC). Methods We collected medical records of patients diagnosed with ASUC according to Truelove and Witts criteria from January 2015 to December 2022 across the AOCC and ANZIBDC. We analyzed the incidence, prognosis, and associated risk factors for infection within one year after treatment and discharge for ASUC. Results A total of 676 ASUC patients (mean age 37±17.08, male 379, 56%) were enrolled, with 329 from AOCC (China, Japan, Korea, Taiwan) and 347 from ANZIBDC. Infections occurring within 1 year following ASUC treatment were identified in 65 patients (9.6%), with no difference between the AOCC and ANZIBDC groups. The most common infections included Clostridioides difficile (C. diff) infection (17/65, 26%), CMV colitis (14/65, 21%), and pneumonia (7/65, 10%). The infection group experienced a poorer prognosis, including a higher overall readmission rage (39.3% vs. 92.2%, P < 0.001) and UC-related readmission rate (16.3% vs. 31.3%, P = 0.004), as well as increased mortality during the 1-year follow-up period (1.1% vs. 13.8%, P < 0.001) compared with the non-infection group. Infections occurred more frequently in patients with clinical activity than in those with clinical remission following ASUC treatment (17.2% vs. 6.9%, P < 0.001). In an analysis adjusted for age, gender, and region (AOCC vs. ANZIBDC), significant risk factors for infection after ASUC included combination therapy with an anti-TNF agent and thiopurine at discharge (adjusted hazard ratio [aHR] 3.714, 95% confidence interval [CI] 1.122–8.979, P = 0.03) and clinical activity during the follow-up period (aHR 3.080, 95% CI 1.690–5.614, P < 0.001). Conclusion Infections were common within 1 year following ASUC treatment and associated with high readmission rates and increased risk of mortality. Combination therapy with an anti-TNF agent plus thiopurine at discharge and persistent disease activity were significant risk factors for the development of infection following ASUC treatment. These findings highlight the need for vigilant infection monitoring and inflammation control to improve ASUC outcomes. References 1.Solitano V, Facciorusso A, Jess T, et al. Comparative Risk of Serious Infections With Biologic Agents and Oral Small Molecules in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2023 Apr;21(4):907-921.e2 2.Kucharzik T, Ellul P, Greuter T, et al. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis. 2021 Jun 22;15(6):879-913. 3.Ahuja D, Luo J, Qi Y, et al. Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn's Disease: Secondary Analysis of the PYRAMID Registry. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1286-1294.e4.

Abstract Background There are limited comparisons of clinical outcomes of acute severe ulcerative colitis (ASUC) between East Asian (EA) and Western countries and many currently used scoring systems are based on Western populations. We developed a predictive model using ASUC data from EA patients and assessed its ability to predict clinical outcomes in an Australia/New Zealand (ANZ) cohort. Methods This retrospective international study was conducted across 23 referral hospitals in EA and ANZ. Patients who met Truelove and Witts criteria for ASUC between January 2015 and December 2022 were included. We compared the 1-year colectomy rates and non-response to corticosteroid therapy (NRS) between the EA and ANZ cohorts. Logistic regression analysis was employed to develop predictive models for 1-year colectomy and NRS. Each variable found as an independent predictor in the logistic regression analysis was weighted as score 1 making the scoring system range 0 to 3 or 4. Results A total of 826 patients with ASUC (411 EA and 415 ANZ) were included. The 1-year colectomy rate was significantly lower in the EA group (3.9%) compared to the ANZ group (22.7%, p<0.001), as was the NRS rate (25% vs. 58.9%, p<0.001). In the EA cohort, independent risk factors for 1-year colectomy included female sex, previous exposure to tumor necrosis factor inhibitors, and albumin levels <3 g/dL at admission. For NRS in the EA cohort, independent risk factors included age at diagnosis <37 years, baseline steroid use, albumin levels <2.5 g/dL at admission, and presence of extraintestinal manifestations. The scoring system based on this model did not predict colectomy and NRS risk effectively in the ANZ cohort (p=0.106 and p=0.012, respectively) compared to the EA cohort (p<0.0001 and p=0.001, respectively). In contrast, previously developed predictive models from Europe, including the French colectomy score and the ADMIT-ASC index for NRS, successfully predicted outcomes in the ANZ cohort (p=0.007 and p<0.0001, respectively) but were less effective in the EA cohort (p=0.106 and p=0.026, respectively). Conclusion Clinical outcomes and predictors of ASUC differ between EA and ANZ patients. Further investigation is needed to determine whether these differences arise from variations in management strategies or disease behavior between these groups. References Kim ES, Kim KO, Jang BI, et al. Comparison of 1-Year Colectomy Risk Between the US and Korean Patients with Acute Severe Ulcerative Colitis: A Propensity Score Matching Analysis. Dig Dis Sci 2022;67:2866-2875. Le Baut G, Kirchgesner J, Amiot A, et al. A Scoring System to Determine Patients’ Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol 2021;19:1602-1610 e1601. Adams A, Gupta V, Mohsen W, et al. Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response. Gut 2023;72:433-442.

Abstract Background The utility of infliximab (IFX) therapeutic drug monitoring (TDM) in acute severe ulcerative colitis (ASUC) is unclear. We aimed to assess whether IFX levels are associated with outcomes in ASUC. Methods PREDICT-UC (NCT02770040) was a randomised controlled trial that compared dosing strategies in 138 steroid-refractory ASUC patients.1 Serum and faecal IFX levels were quantified by ELISA (MabTrack level infliximab, Essange Reagents, Netherlands) after conclusion of the trial and correlated with outcomes: IFX response by day 7 (Lichtiger score [LS]<10, with ≥3-point reduction and decrease in rectal bleeding and stool frequency ≤4/day); eventual response by day 14 (LS<10); and colectomy by month 3. Individual IFX clearance was estimated using a two-compartment pharmacokinetic model with fixed V1, V2 and Q. Results 681 serum IFX levels were available across 135 patients; 91 received an initial 5mg/kg and 44 an initial 10mg/kg IFX dose. 85 responded by day 7 and 17 required colectomy by month 3. Post-IFX serum levels were higher on days 1 and 3 (median ug/mL, IQR) in the 10mg/kg group (175.4, 137.2-202.7 and 116.3, 83.4-132.9) compared to the 5mg/kg group (91.8, 77.2-109.4 and 56.0, 46.0-67.0; each P<0.001). Day 1 and day 3 serum IFX levels were not significantly different in responders and non-responders. A higher day 3:day 1 serum IFX ratio predicted response (63.1%, IQR 56.0-72.1 vs 58.1%, IQR 51.6-62.8, P=0.006; AUC 0.67). A lower day 3 serum IFX level predicted colectomy (51.0, IQR 39.2-57.4 vs 69.0, IQR 51.1-101.7, P=0.003; AUC 0.23). IFX clearance using serum levels between days 1-7 was higher in non-responders compared to responders (0.72L/day, IQR 0.55-0.89 vs 0.56L/day, IQR 0.39-0.72, P<0.001) and in patients who had colectomy (P=0.011). Patients with high clearance (≥0.62L/day) were more likely to respond to an initial 10mg/kg vs 5mg/kg IFX dose (RR 1.50, 95%CI 1.01-2.23, P=0.046), and more likely to require colectomy if they received an initial 5mg/kg vs 10mg/kg dose (HR 4.81, 95%CI 1.09-21.37, P=0.039). In patients with high clearance who did not respond initially, response by day 14 was higher in those receiving a second 10mg/kg dose compared to 5mg/kg (10/26 [38%] vs 1/9 [11%]; RR 3.43, 95%CI 1.05-11.19, P=0.041). Day 1 and 3 faecal IFX correlated with IFX clearance (both rho=0.36, both P<0.001), CRP and the UCEIS (including bleeding and erosion/ulcer sub-scores). Conclusion Elevated day 3:day 1 serum IFX ratio was associated with IFX response by day 7. Early IFX clearance predicted IFX response and month 3 colectomy. High IFX clearance may be overcome by higher IFX dosing, resulting in improved response and reduced colectomy rates. Early IFX level quantification can help predict outcomes in ASUC. References 1.Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.

Abstract Background Clinically active inflammatory bowel disease (IBD) impacts 30-50% of women antenatally1,2. Such clinically active disease is associated with an increased risk of adverse pregnancy outcomes, including preterm delivery2. However, the validity of clinical scores to assess antenatal disease activity has been questioned, whilst both faecal calprotectin (FCP) and intestinal ultrasound (IUS) are feasible and accurate in pregnancy3,4. We aimed to assess whether active disease defined by IUS may predict adverse obstetric outcomes in pregnant women with IBD. Methods This international multi-centre prospective cohort study recruited both preconception and pregnant individuals with IBD in Australia and the USA from 2017-2023. Participants underwent clinical assessments and FCP testing six months before conception, in each trimester (T1, T2, and T3), and, when feasible, six weeks postpartum. IUS was performed preconception and in T1 and T2. Clinically active disease in pregnancy was defined by a PGA>1, or a HBI>5 or SCCAI >3. A FCP>100μg/g was considered elevated, and IUS remission was defined as a bowel wall thickness of <3mm in all bowel segments, with normal bowel wall stratification, a lack of extra-mural complications, and an absence of mesenteric fat hypertrophy or hyperaemia. Univariable and multivariable binary logistic regression analyses including relevant confounders were used to determine the independent impact of IUS disease activity on obstetric outcomes. Cohen κ coefficients were used to determine agreement between FCP, IUS and clinical disease activity. Results 379 participants, 200 with Crohn’s Disease (CD), were recruited. Overall, rates of adverse obstetric outcomes were comparable to the general population (Figure 1). Maximal bowel wall thickness (BWT) >6mm in T1 was associated with a three-fold increased risk of neonatal intensive or special care unit admission (RR 3.10;1.27-7.54, p=0.013) and in T2 was associated with a four-fold increased risk of prematurity (4.51; 1.45-14.04, p=0.009). IUS hyperaemia in T2 was associated with a three-fold increase in preeclampsia risk (3.61; 1.07-12.15, p=0.038). FCP >100μg/g in T2 was associated with an increased risk of preterm delivery after adjusting for clinical disease activity (RR 2.90; 1.22-7.50, p=0.028). Agreement between clinical (HBI or SCCAI) and IUS/FCP activity during pregnancy was weak (Figure 2). Conclusion Sub-clinical disease activity identified on IUS in pregnancy is associated with an increased risk of pre-term delivery, with poor agreement between clinical symptoms and objective biomarkers of disease activity during pregnancy. IUS monitoring should be performed as part of routine antenatal IBD care and IUS remission targeted. References 1.Vestergaard T, Julsgaard M, Rosok JF, Vestergaard SV, Helmig RB, Friedman S, Kelsen J. Predictors of disease activity during pregnancy in women with inflammatory bowel disease-a Danish cohort study. Aliment Pharmacol Ther. 2023;57(3):335-344. 2.Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ. Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease. Gastroenterology. 2021;160(4):1131-1139. 3.Flanagan E, Wright EK, Begun J, Bryant RV, An Y-K, Ross AL, Kiburg KV, Bell SJ. Monitoring Inflammatory Bowel Disease in Pregnancy Using Gastrointestinal Ultrasonography. J Crohns Colitis. 2020;14(10):1405-1412. 4.de Voogd F, van Wassenaer EA, Mookhoek A, Bots S, van Gennep S, Löwenberg M, D’Haens GR, Gecse KB. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022;163(6):1569-1581.

Abstract Background Faecal calprotectin (FCP) is routinely used in the management of inflammatory bowel disease; however, its role in acute severe ulcerative colitis (ASUC) is unclear. We aimed to evaluate the relationship between FCP and outcomes in ASUC. Methods We included ASUC patients who were screened/randomised as part of PREDICT-UC (NCT02770040), a randomised controlled trial that evaluated escalated infliximab (IFX) dosing strategies in steroid-refractory ASUC.1 Stool was collected at screening, and in steroid-refractory patients at day 0 (pre-IFX), and days 1, 3, 5, 7, 14, 30 and 42 and months 3, 6, 9 and 12 post-IFX. FCP was quantified by Liaison® XL (Diasorin) and correlated with outcomes. Outcomes included initial IFX response by day 7 (Lichtiger score<10, with ≥3-point reduction and decrease in rectal bleeding and stool frequency ≤4/day), month 3 colectomy and month 3 Mayo remission (partial Mayo ≤1 & Mayo endoscopic score ≤1). Results Of 185 patients with ASUC, 49 were steroid responders while 136 were steroid-refractory and received IFX. Of 136, 85 were initial IFX responders and 17 required colectomy by month 3. Screening FCP was higher in steroid-refractory compared to steroid responsive patients (median [IQR] 3745 [1753-6175] ug/g vs 2305 [826-4400] ug/g, P=0.020). In steroid-refractory patients, day 0 FCP did not correlate with the Mayo endoscopic score or Ulcerative Colitis Endoscopic Index of Severity (UCEIS) but correlated with CRP (rho=0.251, P=0.031) and the erosion/ulcer sub-score of the UCEIS (rho=0.298, P=0.010). In linear mixed modelling, FCP dynamics in the first 3 days differed between IFX responders and non-responders (daily 22% decrease [95% CI 13 to 31%] vs 3% decrease [95% CI -12 to 16%], P=0.018). A higher day 3:day 0 FCP ratio predicted initial IFX non-response (median [IQR] 109 [51-158] % vs 57 [21-92] %, P=0.006, Area under receiver operator characteristic curve [AUROC]=0.72). FCP dynamics in the first 2 weeks after IFX differed in patients who avoided vs required colectomy (weekly 59% decrease, 95% CI 52 to 65% vs 6% decrease, 95% CI -76 to 50%; P=0.012). Month 3 colectomy was predicted by a higher day 7 FCP (AUROC 0.71, 95% CI 0.49-0.92, P=0.044) and a higher day 3:day 0 FCP ratio (AUROC 0.75, 95% CI 0.58-0.91, P=0.018). Mayo remission at 3 months was predicted by lower day 14 FCP (AUROC 0.31, P=0.004) and day 14:day 0 ratio (AUROC 0.27, P=0.006). Conclusion FCP level and dynamics are novel predictors of outcomes in ASUC. Decrease in FCP by day 3 after IFX predicts initial response. Absolute day 7 FCP and early dynamics predict colectomy. Absolute day 14 FCP and FCP dynamics by day 14 predict month 3 Mayo remission and may help identify patients who may benefit from treatment optimisation. References 1.Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.

Abstract Background Exposure to maternal inflammation in-utero is associated with an increased risk of neurocognitive developmental disorders in offspring, including cerebral palsy (CP). An increased risk of CP and neurological morbidity has been reported in infants of women with CD and UC in registry but not prospective cohort studies. Unsedated neonatal cerebral MRI (nMRI) allows for early assessment of brain microstructural integrity, with bipartietal diameter (BPD) predictive of cognitive and motor outcomes in preterm infants. Generalised movement assessments evaluate the character of infant’s spontaneous movements, can be undertaken remotely by parents with app-based technology (BabyMoves (BM) and are an early indicator of being high risk for cerebral palsy. nMRI & BM have not been used to screen for adverse neurocognitive outcomes in infants born to women with inflammatory disorders. We aimed to assess the feasibility of nMRI and BM in infants born to women with IBD and correlate abnormalities with maternal biochemical inflammation antenatally. Methods Pregnant women with IBD were assessed clinically and biochemically (faecal calprotectin (FC), CRP) in each trimester of pregnancy in this single centre prospective pilot study. Biochemically active disease was defined by FC >100ug/g or CRP >15mg/L. Infants underwent nMRI using a 1.5T MRI with T1-weighted and T2/proton density-weighted sequences performed at 6-12 weeks post-corrected term. Parents filmed 2 BM videos at 12-14 & 14-16 weeks post-corrected term. nMRIs (Figure 1) and BMs were scored by blinded reviewers with validated scoring systems. Metric nMRI data were corrected for gestational age (cGA). Descriptive statistics and spearman correlation coefficients were performed. Results 40 mother-baby pairs, 19 with CD & 20 exposed to a biologic drug, were recruited. Most patients were in biochemical remission throughout pregnancy with median FC <50ug/g and <13% having a CRP >15g/L in trimesters 1-3. At delivery 2/40 infants were premature, 4/40 low birth weight & 3/40 required neonatal intensive care. The median cGA at nMRI was 46 weeks 6 days (range 42 + 5-53 + 4). 2/39 MRI were of insufficient quality for scoring. 5/37 nMRI and 4/35 BM were abnormal, with 1/7 having a clinically significant adverse outcome (Table 1). Biparietal diameter did not correlate with maternal CRP or FC in any trimester of pregnancy. Conclusion nMRI & BM for infant neurocognitive disorder screening is feasible in the setting of maternal IBD. In this cohort of 40 infants, one clinically significant abnormality was identified in an infant of a mother with inactive IBD. Larger studies are required to stratify the risk of adverse neurocognitive outcomes in infants born to women with maternal inflammatory disorders.

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is a life-threatening complication of UC. Previous research has shown that body composition parameters, including sarcopaenia, are associated with outcomes in IBD. However, the relationship between body composition and the clinical outcomes of patients hospitalised with ASUC has not yet been clearly defined. We sought to further evaluate the prognostic role of body composition and further explore predictors of clinical outcome in ASUC. Methods We performed a cohort study of hospitalised ASUC patients. Body composition was assessed using fat and muscle segmentation, at the level of the L3 vertebral body, in patients who underwent abdominal computed tomography (CT) during hospitalisation. We defined sarcopenia according to skeletal muscle index (SMI) < 38 cm2/m2 in females and < 42 cm2/m2 in males. Clinical endpoints included length of hospitalisation, need for rescue medical therapy or colectomy. Between group comparisons were performed and logistic regression was used for risk factor analysis. Results We studied 116 patients with ASUC, 51 of whom underwent abdominal CT imaging during their hospitalisation. Median age was 32 years and 64% of patients were female. Sixty-two patients (53.5%) required rescue medical therapy. Rescue medical therapy was successful in 48 patients (77.4%) and 14 patients (22.6%) required an inpatient colectomy. Patients who underwent CT imaging during admission required increased rescue medical therapy (66.7% vs 43.1%, p=0.02) and were hospitalised for longer (11 vs 6 days, p<0.001). Compared to non-sarcopaenic patients, sarcopaenic patients did not require increased rescue medical therapy (60.7 % vs 79 %, p= 0.22) nor longer median hospitalisation (10.5 vs 11.4 days, p=0.69). We observed a trend towards increased rescue therapy failure in patients with sarcopaenia (52.9% vs 33.3%, p=0.31). Higher Mayo score at presentation was associated with increased need for rescue medical therapy (OR 2.18, 95%CI: 1.43-3.33, p<0.001) and an increasing C-reactive protein (CRP) to albumin ratio predicted prolonged length of stay (OR 1.44, 95%CI: 1.18-1.77, p=<0.001). Conclusion Sarcopaenia did not predict ASUC outcomes in this cohort. Higher Mayo score and increased CRP to albumin ratio at admission predicted prolonged hospitalisation and need for rescue medical therapy.

Abstract Background Strictures are the commonest complication in Crohn’s disease. Surgery and endoscopic dilation are the main treatments; drug therapy has been considered contra-indicated. Given that most strictures have an inflammatory component we aimed to assess the efficacy of anti-inflammatory therapy, and to identify the optimal treatment. Methods In this randomised trial patients with symptomatic Crohn’s disease strictures and inflammation were assessed by imaging (MRI, colonoscopy, intestinal ultrasound) and for inflammation (faecal calprotectin and CRP). Symptoms were assessed using an Obstructive Symptom Score (OSS). Patients with short endoscopically-accessible strictures had a baseline endoscopic balloon dilation if indicated. Patients were then randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with therapy increased for ongoing inflammation at 4 and 8 months, versus standard dose adalimumab mono-therapy. At 12 months primary endpoint was improved OSS. Secondary outcomes: disease activity, treatment failure, stricture morphology, inflammation, psychological well-being, disability, and quality of life. MRI was assessed blindly. Results 52 patients were randomised to the intensive and 25 to the standard treatment arm. 27 of 52 (52%) intensive treatment patients dose escalated at 4 or 8 months. Improved OSS at 12 months occurred in 41 (79%) intensive treatment and 16 (64%) standard treatment arms (P=0.17). Treatment failure was less common in the intensive treatment arm (10%) versus the standard treatment arm (28%) (P=0·045). Faecal calprotectin normalised (<100mcg/g) in 32 (62%) v 11 (44%) (P=0.15), and CRP normalised in 32 (62%) v 11 (44%) (P=0.15), in intensive versus standard treatment arms respectively. MRI stricture morphology improvement (MaRIA score decrease ≥25%) was seen in 31 (61%) v 9 (28%) (P=0.009) and in 40 (78%) v 14 (56%) using the simplified MaRIA score (≥1 point improvement) (P=0.047). Improvement in bowel wall thickness by >25% on ultrasound was seen in 22/43 (51%) and 7/21 (33%) respectively (P=0.18). MRI complete stricture resolution was seen in 10/51 (20%) and 4/25 (16%) (P=0.7). At 12 month colonoscopy 22/48 (46%) v 9/25 (36%) strictures were passable (P=0.42). 12 month median drug levels were 13.2µg/ml and 6.6µg/ml respectively (P<0.0001). See summary results figure 1 and case example figure 2. Conclusion Crohn’s disease strictures are responsive to drug therapy. A majority of patients experience symptom improvement and many have improved stricture morphology. Treat-to-target therapy intensification results in less treatment failure, less stricture-associated inflammation, and greater improvement in stricture morphology.

Abstract Background Gastrointestinal ultrasound (GIUS) can accurately assess disease activity in atients with ulcerative colitis (UC). The aim of this study was to determine the accuracy of GIUS in predicting IV corticosteroid (CS) failure in patients with Acute Severe Ulcerative Colitis (ASUC) and the requirement for rescue therapy. Methods We conducted a multi-centre prospective observational cohort study of adult ASUC admitted to hospital between November 2019 to July 2022. GIUS was performed at six time points for each patient: at hospital admission (SV1), day 3 (SV2), at discharge (SV3), and thereafter during outpatient review in the 10 months of follow-up. Medical rescue therapy was given at the discretion of treating physician according to best clinical practice. Results A total of 32 consecutive patients with ASUC were recruited with a median follow-up duration of 8.9 months: median age 32 years, 38% male and median duration of disease 19 months. Seven patients had newly diagnosed UC and six patients (19%) were biologic experienced. Sixteen patients (50%) were CS responders and the remainder required medical rescue therapy; two patients required colectomy. The median time to rescue therapy and colectomy was 3.5 and 11 days from admission, respectively. At SV1, the median BWT of the worst affected segment was similar between CS responders and non-responders (5.50mm vs 5.85mm, p=0.66), however at SV2, responders had a significantly lower BWT (3.85mm vs 5.05mm, p=0.02). CS responders demonstrated a significant reduction in width of the muscularis propria (p=0.02) and submucosal (p=0.006) layer, but not the mucosal (p=0.61) layer (Figure 1). CS non-responders had a smaller absolute and relative reduction in median BWT at SV2. Receiver operating characteristic curve analysis showed that an absolute reduction of <1.40mm (Sn 63%, Sp 75%, AUROC 0.76) or a relative BWT reduction of <20% (Sn 81%, Sp 75%, AUROC 0.78) predicted CS non-response and need for rescue therapy well. A reduction in BWT and the absence of doppler activity at SV2 further enhanced the predictive capability of GIUS (Sn 81.3%, Sp 87.5%, AUROC 0.91) (Figure 2). Conclusion This study demonstrates the predictive utility of early GIUS in the management of ASUC. A reduction in absolute BWT of <1.40mm or relative BWT of <20% at 36-48 hours of admission identifies CS non-responders with good sensitivity and specificity. BWT reduction at SV2 in responders was driven mainly by decreased muscularis propria and submucosal thickness. Accuracy is further augmented when reduction in BWT and resolution of doppler signal are combined. This study suggests GIUS may allow clinicians to expedite initiation of rescue therapy for patients requiring salvage treatment.