Outcomes In Crohn Research Articles

Optimizing Treatment Outcomes in Crohn's Disease: A Comprehensive Systematic Review and Meta-Analysis of Regenerative Therapies with Emphasis on Platelet-Rich Plasma.

Crohn's disease (CD) is a chronic inflammatory disorder that significantly affects patients' quality of life; conventional treatments often provide limited relief. This systematic review and meta-analysis explored the potential of regenerative therapies, particularly platelet-rich plasma (PRP), as an adjunctive treatment for CD. The study protocol was registered with PROSPERO (CRD42024576683), and a comprehensive search was conducted across major databases, such as PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included terms related to CD and PRP. Studies assessing the efficacy of PRP in CD treatment were selected. Statistical analysis was conducted using the PICO framework with R software (version 4.3.2) and meta-package. Of the 29 studies identified, 10 met the inclusion criteria, comprising pilot studies and controlled trials. Nine studies focused on Crohn's disease perianal fistulas (CDPF), and one focused on colonic CD. Among 138 patients with CDPF, 82.44% showed some fistula healing after PRP treatment, with 48.05% achieving complete resolution. In a sub-analysis, combining PRP with a stromal vascular fraction (SVF) resulted in a 58.62% complete healing rate, whereas combining PRP with adipose-derived stem cells (ASCs) showed even higher efficacy at 85.89%. PRP treatment alone resulted in a lower complete healing rate of 38.51%. PRP was well tolerated, with minor side effects such as localized pain. These findings suggest that PRP, especially when combined with stem cells, offers a promising new approach for treating CD. However, larger trials are needed to confirm its long-term benefits and refine its clinical applications.

Assessment of outcomes in Crohn's disease: A systematic review of randomized clinical trials to inform a multiple outcome framework.

Longstanding disease control in Crohn's disease (CD) is challenging and requires understanding treatment efficacy and outcomes assessment. With multiple novel therapeutic options, rigorous evaluation of outcomes in randomized controlled trials (RCTs) is crucial to inform clinical practice. This study systematically reviewed RCTs focusing on CD outcomes to elucidate the breadth and depth of reported outcomes and measurement instruments. A systematic search was conducted on MEDLINE and Scopus for RCTs published from 1 January 2000 to 31 January 2023. Eligible studies included full-text articles with at least 50 adult CD patients. Primary and secondary outcomes, along with their measurement instruments, were categorized according to the Outcome Measures in Rheumatology Filter 2.1 framework. From 88 included studies, 393 outcomes were analyzed. Clinical outcomes, such as clinical remission and response, were the most prevalent (50.6%); biomarkers (11.5%) and patient-reported outcomes (10.2%) were also assessed. Other outcomes included disease behavior and complications (2%), endoscopy (10.4%), histology (0.5%), radiology (1.3%), healthcare utilization (3.8%), and therapy-related safety (6.9%). Composite outcomes showed an increasing trend, reflecting a shift toward comprehensive evaluations. Coprimary endpoints, including clinical symptoms and mucosal inflammation, were reported in 21 of 88 studies. This review highlights the evolving landscape of outcome assessment in CD RCTs, emphasizing the increasing complexity of outcomes. The prominence of composite outcomes underscores efforts to capture the multidimensional nature of CD. These findings will inform the second stage of a two-round e-Delphi aimed at prioritizing key domains and outcomes for developing a multiple-component outcome for RCTs in CD research.

S1395 The Impact of Neutropenia on Outcomes of Crohn’s Disease Treated With Tumor Necrosis Factor Inhibitors: A Propensity Score Matched Analysis from Global Federated Health Research Network

S1395 The Impact of Neutropenia on Outcomes of Crohn’s Disease Treated With Tumor Necrosis Factor Inhibitors: A Propensity Score Matched Analysis from Global Federated Health Research Network

Acute Abdomen in Crohn’s Disease Patients: Short- and Long-Term Outcomes

Abstract The aim of the study was to determine long-term outcome in Crohn’s disease patients hospitalised for acute abdominal pain. Retrospective chart review was made of consecutive Crohn’s disease patients hospitalised for acute abdominal pain at the tertiary referral centre in Eastern Europe. Between 2015 and 2020, 65 patients with Crohn’s disease were admitted at least once to the emergency room because of acute abdominal pain. Thirteen were admitted twice, eight — three times, three — four times, and three — five times. Most patients had ileal involvement. There were two intra-abdominal abscesses. Fifty-three of 65 underwent abdominal imaging. Forty-five were treated with antibiotics (65%), 17 with steroids (26%), eight received a nasogastric tube and three — parenteral nutrition. Six underwent an intestinal resection during the initial hospitalisation (9%). The hospitalisation length median was eight days and significantly longer in those who underwent surgery (28 vs. 9, p = 0.003). The median follow-up time was 42.8 months. During the follow-up period, 26 (40%) readmitted for abdominal emergencies, 14 underwent surgery — either at the initial or later hospitalisation (21%). Thirteen of 14 surgeries were emergencies, and three were concluded by ostomy formation (21%). One developed postoperative intra-abdominal complication, and two died postoperatively (14%). Complicated disease was associated with hospital readmission (HR, 5.8, 95% CI:1.4–23.3; p = 0.013) and enhanced probability to undergo intestinal surgery (HR, 10.3, 95% CI: 2.4–44.1; p = 0.002). An elevated CRP was associated with decreased risk of hospital readmission (HR, 0.08, 95% CI: 0.01–0.55; p = 0.010). Ileocolic disease was the main cause of hospitalisation for acute abdominal pain. Complicated (stricturing or penetrating) disease should be diagnosed early and surveilled closely.

Mucosal and Transmural Healing and Long-term Outcomes in Crohn's Disease.

Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease. Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease. A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH. Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.

Relationship between Ustekinumab trough concentrations and clinical, biochemical and endoscopic outcomes in Crohn's disease: A multi-center nationwide retrospective study (TARGET STUDY).

Ustekinumab has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real-life. We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6 mg/kg intravenous induction followed by 90 mg every 4-, 8-, or 12-weeks during maintenance were included. We assessed clinical, biochemical, and endoscopic outcomes. Trough concentrations of ustekinumab that were taken from week 42 to week 52 were measured. Primary outcome was to evaluate the relationship between ustekinumab trough concentrations and clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes. A total of 137 patients with CD, median age of 32 years and 83 (60.6%) males. The median serum levels of ustekinumab measured was 7.2 mcg/mL (interquartile range [IQR] 3.1-9.6). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and simple endoscopic score (SES-CD) (r = -0.464, P < .001). Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by Harvey-Bradshaw index (HBI) score (r = -0.582, P < .001), C-Reactive Protein (CRP) levels (r = -0.598, P < .001) and fecal calprotectin (FC) levels (r = -0.529, P < .001). A multivariable analysis adjusted for age, sex and body mass index (BMI) showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/mL was associated with 24% increase in the likelihood of having an SES-CD score <3 (OR 1.24, confidence interval [CI] 1.12-1.37, P value < .001), 44% more likely to achieve HBI score <5 (OR 1.44, CI 1.26-1.65, P value < .001), 52% higher likelihood of CRP more than 10 (OR 1.52, CI 1.31-1.77, P < .001), and 42% increased likelihood of FC more than 250 (OR 1.42, CI 1.24-1.62, P < .001). Ustekinumab trough concentrations above 4.5 mcg/mL were associated with clinical, biochemical and endoscopic remission in CD. Prospective data is warranted to confirm these findings.

The role of proactive therapeutic drug monitoring in guiding infliximab therapeutic optimization in pediatric patients with Crohn's disease: A retrospective study

AbstractTherapeutic drug monitoring (TDM) plays an important role in guiding treatment plan adjustments and clinical outcomes in Crohn's disease. To evaluate the role of TDM‐guided optimization of infliximab dosage in patients with pediatric Crohn's disease. Medical records of patients with pediatric Crohn's disease who were treated with infliximab and had proactive TDM from June 2020 to June 2022 at the Children's Hospital of Chongqing Medical University were included. Baseline influencing factors for infliximab trough concentration (TC) and clinical outcomes before and after the treatment change were analyzed to assess the value of adjusting treatment in the patients. Forty‐six patients (male‐to‐female ratio = 1.55:1, age &lt;18 years) were included. Univariate and multivariate analyses showed that hormone exposure (odds ratio: 0.042, 95% confidence interval: 0.002–0.924, p = 0.044), perianal lesions (5.813, 0.984–34.349, p = 0.052), simplified endoscopic score for Crohn's disease (1.656, 1.065–2.577, p = 0.025), and total protein (TP) (0.851, 0.749–0.967, p = 0.014) were correlated with infliximab TC. Shortening the treatment interval increased the infliximab TC (pre vs. post = 1.69 ± 0.8 vs. 12.03 ± 6.64, p = 0.001, n = 12) after 93.9 ± 37.47 days, decreased the pediatric Crohn's disease activity index and simplified endoscopic score for Crohn's disease, and increased the biochemical remission, clinical remission, endoscopic remission, and endoscopic response rates; however, there was no statistical significance. Hormone exposure, perianal lesions, simplified endoscopic score for Crohn's disease, and TP levels before the first infliximab use affected the infliximab TC. Shortening the treatment interval can improve infliximab TC levels and clinical outcomes.

Factors Predicting Loss of Remission in Crohn's Disease Patients in Endoscopic Remission in the Real World: Results From TARGET-IBD.

There is limited evidence that histologic remission improves outcomes in Crohn's disease (CD). We aimed to characterize a cohort of patients with CD in endoscopic remission and explore factors associated with subsequent loss of remission (LOR). In total, 4474 patients were enrolled in TARGET-IBD, a longitudinal, observational cohort study. Patients with a normal steroid-free colonoscopy (index) were defined as "in endoscopic remission" and were followed for LOR, defined as presence of inflammation, erosion, ulceration, or stricturing on a subsequent colonoscopy or commencement of steroids. Histologic activity was dichotomized using standard of care reports for active inflammation. Unadjusted and multivariable-adjusted Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of LOR in relation to independent variables. Of 658 patients with CD with steroid-free endoscopic remission, the majority were female (57%), white (83%), non-Hispanic (93%); 20% had ileal and 20% isolated colonic disease. Inflammatory (B1) disease was the most common phenotype (43%). Of these 658 patients, 257 (39%) had histologic inflammation on index colonoscopy. Histologic inflammation at index colonoscopy was associated with nearly twice the LOR risk (HR 1.96, 95% CI: 1.50-2.57) with median time to relapse of 1.20 years. Biologic use at index was associated with lower LOR risk (monotherapy, HR 0.61, 95% CI: 0.45-0.82; combination therapy, HR 0.43, 95% CI: 0.28-0.66). Active histologic inflammation despite endoscopic remission, and lack of biologic use were independently associated with risk of subsequent LOR, providing evidence that histologic remission may impart improved outcomes in patients with CD.

Magnetic resonance enterography findings 46 weeks after initiation of biological therapy predict long-term adverse outcomes in Crohn's disease.

Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes. Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years. A logistic regression analysis was performed to assess the prognostic value of different radiologic findings for various predefined adverse outcomes. Of the 89 patients included, 46 (51.7%) had ≥1 adverse outcome during follow-up: 40 (44.9%) had clinical recurrence; 18 (20.2%) required surgery, 8 (9%) endoscopic balloon dilation, 12 (13.5%) hospitalization and 7 (7.8%) required corticosteroids. In the multivariate analysis, persistence of severe lesions (MaRIA ≥11) in any intestinal segment was associated with an increased risk of surgery [OR 11.6 (1.5-92.4)], of surgery and/or endoscopic balloon dilation [OR 6.3 (1.3-30.2)], and of clinical relapse [OR 4.6 (1.6-13.9)]. Penetrating lesions were associated with surgery [OR 3.4 (1.2-9.9)]. Creeping fat with hospitalization [OR 5.1 (1.1-25.0)] and corticosteroids requirement [OR 16.0 (1.2-210.0)]. The presence of complications (stricturing and/or penetrating lesions) was associated with having ≥1 adverse outcome [OR 3.35 (1.3-8.5)]. MRE findings at week-46 after initiating biological therapy can predict long-term adverse outcomes in CD. Therapeutic intervention may be required in patients with persistence of severe inflammatory lesions, CD-associated complications, or creeping fat.

Racial and Ethnic Disparities in Health-Related Outcomes in Crohn's Disease: Results From the National Health and Wellness Survey.

Crohn's disease (CD) is a chronic inflammatory condition affecting the entire gastrointestinal tract that is associated with significant humanistic, clinical, and economic burdens. Few studies have assessed the association between CD severity and patient-reported outcomes (PROs), healthcare resource utilization (HCRU), and medical costs; even fewer have examined differences in disease outcomes among patients of various racial/ethnic groups. In this cross-sectional study, sociodemographic data, PROs, and economic outcomes for participants with self-reported CD were collected from the National Health and Wellness Survey (2018-2020). Multivariable analyses were used to assess the association of CD severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), HCRU, and medical costs. Analyses included 1077 participants with CD (818 non-Hispanic White, 109 non-Hispanic Black, and 150 Hispanic). Participants with self-reported moderate/severe CD reported significantly worse HRQoL and WPAI, greater HCRU, and higher medical costs than those with self-reported mild CD. Non-Hispanic Black participants reported better HRQoL and fewer healthcare provider visits than non-Hispanic White participants. There were no significant differences in PROs between non-Hispanic White and Hispanic groups. Interactions between race/ethnicity and CD severity emerged for some, but not all groups: Specifically, non-Hispanic Black participants with moderate/severe CD reported greater absenteeism and more gastroenterologist visits than non-Hispanic Black participants with mild CD. Participants with moderate/severe CD reported worse PROs, greater HCRU, and higher medical costs than those with mild CD. Additionally, racial/ethnic differences were found across several HCRU and economic outcomes. Further research is needed to better understand factors contributing to burden among patients with varying CD severity across racial/ethnic groups.

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.

Parenteral n–3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn’s disease after bowel resection: a randomized, unblinded controlled clinical trial

BackgroundThe postoperative inflammatory response is associated with postoperative recovery in surgery. n–3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n–3 polyunsaturated fatty acids supplementation on outcomes in Crohn’s disease after bowel resection is unclear. ObjectivesWe aimed to investigate the effects of postoperative parenteral n–3 polyunsaturated fatty acids supplementation in Crohn’s disease. MethodsA prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn’s disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n–3 polyunsaturated fatty acids supplementation for 5 d postoperatively. ResultsThere were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n–3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention–to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n–3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1β (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. ConclusionsParenteral n–3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn’s disease following bowel resection, with fewer complications and reduced inflammatory cytokines.This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic.clinicaltrials.gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

P263 Clinical-Endoscopic Correlation of Postoperative Recurrence in Surgically Treated Crohn's Disease Patients

Abstract Background The majority of patients with Crohn's disease (CD) require surgical intervention at some point in their disease course, particularly ileocolic resection. However, the average rate of clinical postoperative relapse is 30% at 3 years and 60% at 10 years. Endoscopic postoperative recurrence precedes clinical recurrence, highlighting the importance of conducting a colonoscopy 6 to 12 months postoperatively to establish the Rutgeerts score,which predicts the risk of clinical recurrence. The aim of this study is to correlate endoscopic findings with the clinical symptoms of these patients. Methods We retrospectively analyzed clinical symptoms and Rutgeerts scores of Crohn's disease patients who underwent ileocolic resection during the course of their disease, and followed at the Hepato-Gastroenterology Department of MOHAMMED VI university hospital in Oujda, Morocco, during the period [2018-2023] Results Sixty Crohn's disease patients underwent at least one surgical operation during the course of their disease, comprising 25 females and 35 males with a sex ratio (M/F: 1.4). The average age of our patients was 35 years [20-73]. The average time between diagnosis and the first surgery was 4 years. All these patients received postoperative medical treatment before colonoscopy, including azathioprine or methotrexate in 26 patients (43%) and anti-TNF in 34 cases (56%), with an average time of 8 months between surgery and the start of treatment. According to the Montreal classification, the ileocolic form dominated in 88% of cases, with a penetrating phenotype in 40% and a structuring phenotype in 60%. The operative indication was primarily obstructive syndromes in 85% of cases and collections in15%. The average time to perform colonoscopy after surgery was 10 months. During follow-up, 80% of patients were asymptomatic post-surgery, with Rutgeerts scores of I0-I1 in 11(23%) patients, I2 in 13 (27%) cases, I3 in 9 (19%) cases, and I4 in 15 (31%) cases.However, clinical recurrence, characterized by diarrhea, abdominal pain, or Koenig's syndrome, was observed in 20% of patients, with an average postoperative clinical recurrence time of 2 years. The endoscopic findings in these patients revealed Rutgeerts scores of I2 in 4 cases (33%), I3 in 3 cases (25%), and I4 in 5 cases (41%). Conclusion In summary, despite postoperative medical management, the risk of clinical recurrence isnotable. Early postoperative colonoscopy, assessing Rutgeerts scores, proves crucial inpredicting clinical recurrence risk. The observed clinical-endoscopic discordance emphasizes the need for a comprehensive approach to monitoring postoperative outcomes in Crohn's disease.

P966 The intra-patient variability of adalimumab clearance during an intensive sampling study of Crohn’s disease patients receiving maintenance therapy

Abstract Background Lower adalimumab (ADA) clearance (CL) is associated with improved outcomes in Crohn’s disease (CD) and may be a superior pharmacokinetic (PK) measure than ADA concentrations. We compared intra-patient variability in ADA CL and concentrations within a 14-day treatment cycle and across two consecutive cycles under maintenance treatment. Methods In a previous PK study of CD patients receiving maintenance ADA 40mg fortnightly, samples were collected intensively at 3 visits (day 4-6, 7-9, and 13-14 post dose) across 2 consecutive cycles. Available sera from this cohort were subsequently used to measure ADA concentrations (lower limit quantification: &amp;lt;1.6 µg/mL) and antibody to adalimumab (ATA) status using a drug tolerant homogeneous mobility shift assay, and albumin. Apparent ADA CL (L/day) was calculated incorporating these measure parameters in a nonlinear mixed effect model with Bayesian priors (under steady state assumption) with dose and inter-dose interval with ATA and albumin as covariate. Rates of sustained clinical and biochemical remission (Harvey Bradshaw Index (HBI) score consistently &amp;lt;5 and CRP levels consistently &amp;lt;3 mg/L) were estimated for each patient. Longitudinal changes in PK parameters within-and-across cycles were evaluated using intra-patient coefficient of variation and linear mixed effect models. Results Sera was available from 70 study visits in 12 patients (6 males, mean age 36 years). Median ADA concentrations and CL were 8 µg/mL (IQR 6.0-10.4) and 0.374 L/day (IQR 0.29-0.43), respectively, with ATA detected in one patient (#9). Estimated ADA concentrations and CL is presented in the Table. Intra-patient variability in CL was much lower across the two 14-day cycle (9% and 7%, respectively) compared to intra-patient variability in ADA concentration (15% and 13%, respectively). Linear mixed effect models confirmed these findings with no impact of sampling time on CL (intercept=0.46±0.12 L/day; slope estimate=0.002±0.002 L/day; p=0.16) as compared to significant change in ADA concentrations (intercept=10.6±1.2 µg/mL; slope estimate=-0.25±0.03 µg/mL; p&amp;lt;0.01) over inter-dose interval sampling time. Sustained clinical and biochemical remission was achieved in 5/12 patients (42%); none presented with CL &amp;gt;0.8 L/day (a cut-off previously associated with worse outcomes). Of 7 patients without sustained clinical and biochemical remission, two presented with optimal concentrations (&amp;gt; 10 µg/mL), thus suggestive of mechanistic failure, and one developed ATA, lower concentration and higher ADA CL. Conclusion CL is subject to less intra-patient variability than ADA concentrations, supporting its assessment at any time point within a 14-day treatment cycle.

P802 Impact of early use of immunomodulator on the outcomes of Crohn's disease: A Systematic Review and Meta-Analysis

Abstract Background Although immunomodulators play a crucial role in the treatment of Crohn's disease, robust evidence regarding the impact of early use of immunomodulators on its outcomes is still limited. Methods We searched MEDLINE, EMBASE, and the COCHRANE library to identify articles analyzing clinical outcomes according to the timing of immunomodulator administration in Crohn's disease. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs]. Types of immunomodulators include thiopurines or methotrexate. Results A total of 7 studies were identified as eligible for the meta-analysis. Early immunomodulator administration within 1 to 3 years after diagnosis was associated with a lower risk of bowel resection surgery (HRs 0.57, 95% confidence interval [CI] 0.45-0.71), but it was not associated with a lower risk of perianal surgery (HRs 0.62, 95% CI 0.27 - 1.39). In subgroup analyses, early immunomodulators were effective in lowering the risk of intestinal resection in both adults and the young population. Conclusion Early administration of immunomodulators in Crohn's patients is associated with a lower risk of bowel resection surgery. This finding suggests that when immunomodulators are administered within an optimal therapeutic window, they possess the potential to alter the disease course in Crohn's patients.

P075 Early intestinal ultrasound non-response is a prediction tool of complicated disease outcome in Crohn’s disease patients treated with infliximab

Abstract Background The ultimate goal of Crohn’s disease (CD) treatment is to modify the natural course of disease and prevent complications. We aim to assess the role of intestinal ultrasound (IUS) as predictor tool for complicated disease. Methods Prospective longitudinal study including patients with active CD starting infliximab. Clinical, laboratorial and IUS parameters were assessed at week(W) 0, 14, 30, and 54. The IBUS-SAS score was used to assess ultrasonographic disease activity and includes, among others, bowel wall thickness (BWT) measurement. IUS response was defined as reduction in 25% in BWT and IUS remission as the normalization of BWT (≤3mm), doppler sign (≤1), stratification (BWS), and inflammatory fat in the most affected segment. Ileocolonoscopy was done at W0 and 54. Endoscopic healing (EH) was defined as SES-CD &amp;lt;3. We defined a composite outcome(CO) for complicated disease including development of stricturing or penetrating disease, need for bowel surgery, CD-related hospitalization, or the need to switching due to loss of response to therapy. Results We included 48 patients (48% male; median age 31 years, IQR 26-44). The median follow-up time was 23.5 months(M) (IQR11-38.25). The median time until the development of the outcome was 12M, IQR 9.75-15.25. During follow-up, 37.5% developed the CO (27.1% with stricturing or penetrating disease, 12,5% needed bowel surgery, 18,8% needed hospitalization and 6% switched therapy). Baseline disease behavior (B1:21,2% vs B2/B3:73.3% p&amp;lt;0.001) and a higher IBUS-SAS score (70.34 vs 58.80 p=0.042) were associated with development of CO during follow-up. Patients who developed the CO had a numerically higher BWT throughout the first year of therapy (W14: 5.00mm vs 3.65mm, p=0.007; W30: 4.78mm vs 3.43mm, p=0.007); a higher IBUS-SAS score was also seen at W14, W30 and W54 (57.00 vs 40.35, p= 0.03; 54.74 vs 31.00, p=0.004 and 29.84 vs 23.39, p=0.026, respectively). On survival analysis, IUS remission at W30 (HR 0.27 95% CI (0.76-0.94), p=0.04) and IUS response at W30 (HR 0.27 95% CI (0.09-0.94), p =0.015) were protective for the development of the CO. In multivariate Cox regression, the absence of IUS response at W30 (HR 4.80, 95% CI 1.03-22.45, p=0.046), and EH at W54 (HR 5.70, 95% CI 1.33-24.45, p=0.02) were independent predictors of worse outcome. The best cut-off at W30 to predict the CO was IBUS-SAS &amp;gt;52 (AUC 0.74) and BWT &amp;gt; 4.11 mm (AUC 0.75). Conclusion Early assessment of ultrasonographic response at W30 of therapy can help to predict prognosis in CD. Our results highlight that in the absence of significant IUS response after 6 months of therapy, we should consider treatment intensification and close monitoring to prevent complications.

P794 Relationship between Ustekinumab Trough Concentrations and Clinical, Biochemical and Endoscopic Outcomes in Crohn’s Disease; A Multi-Center Nationwide Study (TARGET STUDY)

Abstract Background Ustekinumab (UST) has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn’s disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real life settings Methods We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6mg/kg intravenous induction followed by 90 mg every 4 or 8 weeks during maintenance were included. Clinical, biochemical, and endoscopic outcomes, trough concentrations of ustekinumab that was taken from week 42 to week 52 were included. Primary outcome was to assess if ustekinumab trough concentrations were associated with clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes Results A total of 137 patients with CD. mean age of 34.1 years and 83 (60.6%) males. The mean serum levels of ustekinumab was 7.2 (SD 4.5). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and SES-CD score (r = -0.464, p &amp;lt; 0.001. Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by HBI score (r = -0.582, p &amp;lt; 0.001), C-Reactive Protein(CRP) levels (r = -0.598, p &amp;lt; 0.001) and fecal calprotectin (FCAL) levels (r = -0.529, p &amp;lt; 0.001). A multivariate analysis adjusted for age, sex and BMI showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/ml was associated with 24% increase in the likelihood of having an SES-CD score less than 3 (OR 1.24, CI 1.12-1.37, P&amp;lt;0.001), 44% more likely to achieve HBI score less than 5 (OR 1.44, CI 1.26-1.65, P&amp;lt;0.001), 52% higher likelihood of CRP less than 10 (OR 1.52, CI 1.31-1.77, p &amp;lt; 0.001), and 42% increased likelihood of FCAL less than 250 (OR 1.42, CI 1.24-1.62, p &amp;lt; 0.001). Conclusion Ustekinumab trough concentrations above 4.5 mcg/ml was associated with clinical, biochemical and endoscopic remission in Crohn’s disease. Prospective data is warranted to confirm these findings

P573 Simplified MARIA score does not predict long-term outcomes in Crohn’s disease patients undergoing modified side-to-side strictureplasty for extensive ileitis

Abstract Background Strictureplasty techniques were developed to limit the risk of short bowel syndrome in Crohn’s disease (CD) patients with affected small intestine. In the setting of extensive small bowel disease, long strictures might be treated with modified side-to-side isoperistaltic strictureplasty (SSIS). We studied long-term outcomes in patients who underwent SSIS and evaluated if radiological features on MR enterography (MRE) predict them. Methods This retrospective study included CD patients who underwent SSIS, for whom preoperative and six-month postoperative MRE were routinely performed. Simplified MARIA (MARIAs) score, considering wall thickness, edema, fat stranding and ulcers (score &amp;gt;1 active CD; maximum 5) was used. Improvement in maximal wall thickness was defined as decrease of at least 30% from baseline. Deep remission was defined as absence of symptoms and endoscopic remission (mRutgeerts score ≤i1), and clinical recurrence as occurrence of new symptoms confirmed by endoscopy (mRutgeerts score ≥i2b) or radiology (new strictures/inflammation) requiring treatment. Clinical data were collected from medical records. The correlation between recurrence and features within the MARIAs score was assessed. Results Thirty CD patients underwent SSIS and had pre- and six-month postoperative MRE (table). Immediately after surgery, 13 (43.3%) patients were continued or initiated on advanced therapy. Over a median [IQR] follow-up of 7.4 [3.3-9.3] years, 17 (56.7%) patients showed clinical recurrence of whom 6 (20.0%) needed surgical reintervention (figure). Deep remission was observed in 8 (26.7%) patients. Preoperatively, all patients had a maximum MARIAs score of 5. After surgery, the median [IQR] change in MARIAs score was 0.0 [0.0-0.8]. Cox regression analysis showed no association between decrease in overall MARIAs score, nor separate components of this score, with clinical or surgical recurrence free survival. Wall thickness decrease of &amp;gt;30%, observed in 15 (50%) patients, showed a trend for clinical recurrence free survival (p=0.098). Three patients showed normalization of MARIAs score and showed no recurrence thereafter. None of the clinical variables collected showed significant association with recurrence, except for immediate postoperative advanced therapy which had a 70% protection from clinical recurrence [p=0.036 / HR 0.3 (0.097-0.92)]. Conclusion Long-term follow-up of CD patients undergoing SSIS showed that 57% of patients had clinical recurrence and 20% needed surgical reintervention. The MARIAs score was not predictive of long-term postoperative clinical or surgical recurrence as most features of the score remained unaltered. These shortcomings of the MARIAs score should be addressed when designing improved scoring tools.

Treat to target in Crohn's disease: A practical guide for clinicians.

A treat-to-target (T2T) approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II guidelines specify short, intermediate, and long-term treatment goals, documenting specific treatment targets to be achieved at each of these timepoints. Scheduled appraisal of Crohn's disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified. Consensus treatment targets in Crohn's disease comprise combination clinical and patient-reported outcome remission, in conjunction with biomarker normalisation and endoscopic healing. Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing, clinicians must consider that this may not always be appropriate, acceptable, or achievable in all patients. This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets. The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques, particularly intestinal ultrasound, holds great promise; as do emerging treatment targets such as transmural healing. Two randomised clinical trials, namely, CALM and STARDUST, have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn's disease. Findings from these studies reflect that patient subgroups and Crohn's disease characteristics likely to benefit most from a T2T approach, remain to be clarified. Moreover, outside of clinical trials, data pertaining to the real-world effectiveness of a T2T approach remains scare, highlighting the need for pragmatic real-world studies. Despite the obvious promise of a T2T approach, a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake. This highlights the need to describe strategies, processes, and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice. Hence, this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn's disease.

Shorter Crohn’s Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies

Early biologic therapy treatment has demonstrated better outcomes in Crohn's disease (CD). We evaluated the impact of CD duration in patients with moderately to severely active CD treated with risankizumab therapy. This post hoc analysis evaluated clinical, endoscopic, and safety outcomes by baseline CD duration (<2, 2-5, >5-10, and >10 years) in patients from ADVANCE, MOTIVATE, and FORTIFY. Pooled induction analyses included patients who received intravenous 600-mg dose of risankizumab or placebo for 12 weeks. Maintenance analyses included patients who responded to induction risankizumab and received subcutaneous 180-mg or 360-mg dose of risankizumab for 52 weeks. Duration subgroups were compared using Cochrane-Armitage trend tests with nominal P values. Among 527 patients who received risankizumab 600-mg induction therapy, higher outcome rates were observed at week 12 among patients with shorter vs longer baseline disease duration (for <2, 2-5, >5-10, and >10 years, clinical remission: 42.7%, 46.9%, 43.5%, and 33.2% [P= .046]; endoscopic response: 48.3%, 36.3%, 32.0%, and 33.4% [P= .025]). Among 298 patients receiving risankizumab (180 mg or 360 mg) maintenance therapy, shorter vs longer baseline disease duration was generally associated with numerically higher endoscopic outcome rates at week 52. Higher clinical remission and endoscopic outcome rates were generally observed with shorter disease duration with 180-mg risankizumab dose only. Adverse event rates were generally similar across duration subgroups. Clinical benefits of risankizumab are observed across disease duration subgroups; clinical and endoscopic outcome rates are higher with risankizumab initiation earlier in the disease course (ClinicalTrials.gov numbers: NCT03105128, NCT03104413, and NCT03105102).