Outcomes In Inflammatory Bowel Disease Research Articles

P248 Feasibility, accuracy and reproducibility of the ultrasound measurement of psoas muscle compared to bioelectrical impedance analysis for the evaluation of skeletal muscle mass in patients with IBD

Abstract Background Sarcopenia is characterized by the loss of muscle mass and it is a strong predictor of disability and poor outcomes in several chronic gastrointestinal diseases such as inflammatory bowel diseases (IBD). Therefore, it is useful to evaluate muscle mass in patients with chronic gastrointestinal diseases at risk for sarcopenia. Radiological evaluation of muscle mass is obtained with computed tomography (CT), magnetic resonance (MRI) and bioelectrical impedance (BIA). We aimed at assessing the feasibility, reproducibility and diagnostic accuracy of ultrasound (US) measurement of psoas muscle thickness adjusted for body mass index (BMI) compared to skeletal muscle mass (SMM) evaluated with BIA normalized to height2 in the quantification of muscle mass among patients with IBD. Methods We enrolled a total of 86 consecutive patients with IBD (males 68.6%, mean age 50.4 ± 17.6, 7.4% with Crohn’s disease) who underwent US evaluation of psoas muscle thickness and BIA during the same day. US measurement (Philips Epiq, Bothell, USA) was performed by two sonographers, blind to each other. BIA was performed with the Seca mBCA 525 (Hamburg, Germany). A cut-off of 6.68 and 8.97 of SMM normalized to height2 was considered as normal value for women and men respectively. Sensitivity, specificity, positive and negative predictive values(PPV and NPV), positive and negative likelihood ratios (LR+ andLR−) were calculated, all with the respective 95% confidence inter-vals (95% CI). The reproducibility between the US operators was evaluated by intra-class correlation coefficient(ICC) for the quantitative variables of psoas muscle. The study was approved by our local ethics committee and partially funded by the Italian Ministry of Health. Results US psoas muscle thickness measurement was feasible in all the 86 enrolled patients. There was a significant correlation between US measurement and BIA with a Pearson r coefficient of 0.54 (p= <0.0001). Among men a cut off of 108.18 cmxkg/m*2 showed a sensitivity of 93.5% and a specificity of 53,6% in the detection of low SMM at BIA (Figure 1). Among women a cut off of 66.9 cmxkg/m*2 showed a sensitivity of 78.5% and a specificity of 69.2% in the detection of low SMM at BIA (Figure 2). Reproducibility among the operators had an ICC of 0.95 (CI 0.93-0.96). Conclusion Sarcopenia is a prognostic factor of poor outcomes in IBD, therefore it is important to identify patients at risk for it. Nowadays, assessment of muscle mass and eventually sarcopenia relies on radiological techniques (CT/MRI and BIA). At this purpose we propose a simple, non-ionizing, fast and reproducible US technique that compared to BIA showed a high sensitivity and thus can be used in clinical ractice to screen for muscle mass reduction in IBD patients.

P1133 Relative survival and cause-specific mortality of a Chilean Inflammatory Bowel Disease cohort

Abstract Background In the past two decades, multiple studies have shown an improvement in outcomes of inflammatory bowel disease (IBD) patients including a decreasing mortality associated with new treatments, surveillance, and healthcare support. There are no large studies in Latin-American countries addressing survival and death causes in IBD patients. We aimed to assess relative survival (RS) and causes of death in Chilean IBD patients. Methods IBD patients treated in a tertiary reference centre (Pontificia Universidad Católica of Chile, Santiago, Chile) since January 1990 were included in a local database. Death certificates were analysed to obtain the date and specific cause of death. The recorded time started on the date of definitive diagnosis and lasted until death or censoring on December 31st, 2020. The survival of IBD patients was compared with the life expectancy of the Chilean general population based on official life tables collected in the Human Mortality Database (www.mortality.org). The RS was computed using the Ederer II method implemented in the RELSURV package of the R software. A RS greater than 1.0 indicates that the analysed cohort has a higher survival than the expected survival of the reference population for the same age, sex and date at which age was coded. Inclusion of 1.0 within 95% CI indicates no difference between observed and expected survival. Data were also expressed graphically as the observed cumulative survival curves over time and the 95% confidence interval (CI) and compared to the reference population. Results We included 1,289 IBD patients with a media age at diagnosis of 35.9±14 years, 40.9% males and a follow-up of 22,525 patients-year. Ulcerative Colitis, Crohn’s disease and IBD unclassified patients comprised 50.2%, 43.1% and 6.7% of the cohort, respectively. A total of 106 patients (8.9%) died during the study period. Compared with the general population, the survival of IBD patients was higher (RS = 1.04; 95% CI: 1.02-1.07) at 20 years of follow-up (Table and Figure). This higher RS in IBD patients was observed in males and females, as well as CD patients and IBD patients older than 40-year-old (Table). The main causes of death in IBD patients were cancer (34%), infections (27.7%) and cardiovascular diseases (21.3%). Conclusion Compared to the general population, a higher long-term survival was observed in this large cohort of Chilean IBD patients. These findings may be due to a closer surveillance of this group of patients. Causes of death mirrored those in previously reported cohorts; therefore, a special care should be pay on their prevention in Latin-American countries as well.

P468 Relevance of anti-drug antibodies in context of supra-therapeutic anti-TNF concentrations

Abstract Background The low serum concentration of anti-tumor necrosis factor-alpha (anti-TNFα) agents and the presence of anti-drug antibodies are related to poor therapeutic outcomes in inflammatory bowel disease (IBD). We aimed to evaluate the prognosis of patients having both antidrug antibodies and supratherapeutic drug concentrations. Methods IBD patients on maintenance infliximab (IFX) or adalimumab (ADA) therapy were prospectively recruited. Serum drug concentrations and antidrug antibodies were measured (Anser, Prometheus). The drug concentrations were classified as subtherapeutic (IFX: <3 µg/mL; ADA: <5 µg/mL), therapeutic (IFX: 3-8 µg/mL; ADA 5-10 µg/mL), and supratherapeutic (IFX > 8 µg/mL; ADA > 10 µg/mL) concentrations regardless of the timing of blood sample collection. We analysed the relationship between i) drug concentrations and ii) the presence and absence of anti-drug antibodies with use of systemic corticosteroids and anti-TNF discontinuation. Results Of 172 patients (122 CD [70.9%], 44 UC [25.6%], 3 IBD-U [1.7%], and 3 IBD-pouch [1.7%]), the median age was 32.3 years (range, 24.8-42.5), and the median duration of IBD was 9.7 years (range 5.3-15.6). IFX and ADA were used in 81 (47.1%) and 91 (52.9%) patients, respectively, and concurrent usage of immunomodulators and systemic corticosteroids was observed in 39 (22.7%) and 23 (13.4%) patients, respectively. Supratherapeutic, therapeutic, and subtherapeutic concentrations were observed in 74 (43.0%), 32 (18.6%), and 66 (38.4%), respectively. The patients with antidrug antibodies (n = 79, 45.9%) showed a higher frequency of having subtherapeutic drug concentrations (68.4% vs 12.9%, P < 0.001) compared to those without antibodies, and the presence of antibodies was an independent predictor of discontinuation of anti-TNFα agents (hazard ratio 3.50, 95% confidence interval 1.88-6.51, P < 0.001, Fig. 1A). In subgroup analysis, patients with antidrug antibodies and supratherapeutic drug concentration exhibited a tendency to have improved drug persistence compared to those with subtherapeutic drug concentration, albeit insignificantly (P = 0.099, Fig. 1B). However, the persistence in this group was still poorer than that observed in patients without antibodies (P = 0.003). Finally, neither anti-TNFα concentrations nor the presence of antidrug antibodies were associated with the need for additional systemic corticosteroid use within 6 months. Conclusion The presence of antidrug antibodies can predict the discontinuation of anti-TNFα agents despite supratherapeutic drug levels. While supratherapeutic drug concentration may improve the treatment persistence of anti-TNFα agents in patients with anti-drug antibodies, it does not last as long as in those without antibodies.

P261 Co-infection of Clostridioides Difficile Aggravates Poor Outcomes in Inflammatory Bowel Disease with Cytomegalovirus Colitis

Abstract Background Inflammatory bowel disease (IBD) prognosis is adversely affected by both Cytomegalovirus (CMV) colitis and Clostridioides Difficile (CD) infection. This is the first study in Asia to investigate the clinical impact and risk factors associated with their co-infection in IBD patients. Methods We conducted a retrospective cohort study at Linkou Chang Gung Memorial Hospital from January 2000 to May 2021, involving 53 IBD patients diagnosed with CMV colitis through colonic CMV immunohistochemistry staining. Based on stool toxin A/B tests, patients were divided into two groups: CMV only and CMV+CD co-infection. We compared baseline characteristics, clinical manifestations, risk factors, and outcomes between these groups. Logistic regression was used to analyze independent risk factors, and Kaplan-Meier methods evaluated cumulative incidence of remission rates. Results The study included 53 patients (37 in the CMV group and 16 in the Co-infection group). Diarrhea (93.8%) and abdominal pain (87.5%) were more prevalent in the co-infection group. Compared to the CMV group, the co-infection group had higher hospitalization times (2.5 vs. 1, p=0.005), more frequent CMV recurrences (1 vs. 0, p<0.001), and longer durations to achieve clinical (5 vs. 1 months, p<0.001), steroid-free (10 vs. 4 months, p=0.001), endoscopic (17.5 vs. 8.3 months, p=0.011), and histological remission (18 vs. 11 months, p=0.021) (Table 1-1). Kaplan-Meier analysis also indicated similar trends in Figure 1. The use of biologics was identified as an independent risk factor for co-infection (Odds Ratio 13.33, Confidence Interval 1.52-117.15, P=0.02) (Table 1-2). Conclusion Co-infection with CMV and CD in IBD patients leads to significantly worse outcomes. Early identification and aggressive treatment of co-infection in high-risk patients are vital for improving their prognosis.

P625 Electronic patient-reported outcomes in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional German LISTEN II study

Abstract Background Integrating systematic monitoring of patient-reported outcomes (PROs) with clinical information may enhance disease management and improve patient outcomes. Vedolizumab (VDZ) is approved for treating patients with ulcerative colitis (UC) and Crohn’s disease (CD). The German, multicentre, prospective, non-interventional LISTEN II study evaluates patient characteristics and effectiveness of VDZ treatment in real-world clinical practice, focusing on PROs. Methods Adult UC or CD patients, who either initiate VDZ intravenously (IV) or switch from IV maintenance to subcutaneous (SC) formulation, are enrolled. Data on patient characteristics, modalities of VDZ use and disease activity are recorded quarterly over one year. PROs are recorded via weekly questionnaires in app (ePRO). Sustained ePRO use was defined as proportion of patients reporting at least one PRO for ≥80% of available questionnaires. Interim data up to 9 months follow-up are presented. Results Data of 299 UC and 174 CD patients (51% and 59% female, respectively) with a mean age of 40 years were analysed. VDZ treatment was newly initiated IV (start) in 259 UC and 151 CD patients and switched from IV to SC application (switch) by 40 UC and 23 CD patients at baseline. Total mean pMayo score decreased in UC start-patients from 5.0 to 1.7 and from 1.1 to 0.8 in switch-patients. In CD start-patients HBI score decreased from 5.5 to 2.5 and from 3.1 to 2.3 in switch-patients. The ePRO was initially utilized by 226 UC and 124 CD patients (51% and 61% female, 57% and 52% sustained ePRO users, respectively) with a mean age of 39 years; 86% were start- and 14% switch-patients. Disease activity at baseline was comparable to the overall population, showing a total mean pMayo score of 4.5 for UC and a HBI of 5.3 for CD patients. Most UC (82%) and CD patients (88%) used a patient support program for the first time. ePRO use declined to approx. 40% usage within the second quarter and to 30% during further follow-up. Overall, mean symptom scores reported via the ePRO declined during the 9-month follow-up period. The most notable improvements (baseline to month 9) were reported for the symptom impact on work productivity (from 3.9 to 1.7 points) in UC patients and for sick leave (from 1.3 to 0.4 points) in CD patients (Table). For most PROs reduction in symptom scores was apparent within the first week of ePRO-use (Figure). Conclusion LISTEN II real-world data confirm VDZ effectiveness in UC and CD patients, with reduction in disease activity in IV starters and maintained effectiveness in IV-to-SC switchers. Both UC and CD patients reported sustained symptom improvement under VDZ treatment, with scores indicating improvement within the first week of ePRO-use.

P211 Impact of celiac disease on the outcome of Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) and celiac disease (CeD) are digestive disorders that share common genetic, immunological, and environmental factors in their pathogenesis. Objective To investigate whether the concurrent diagnosis of CeD and IBD predisposes to a more aggressive phenotype of IBD. Methods A multicenter case-control study was performed including cases (celiac IBD) and controls (non-celiac IBD) (paired 1:2, matched for sex, year of diagnosis, and IBD type). CeD diagnosis was established if Marsh score was > 1. Disease phenotype and IBD outcomes, including mortality and neoplasm development, were ascertained from medical records. Results 66 patients with celiac IBD (39 females; 30 ulcerative colitis-UC/6 indeterminate colitis-IC/30 Crohn disease-CD; age at diagnosis 30±14 years) and 132 matched non-celiac IBD patients (85 females; 68 UC/4 IC/60 CD; age at diagnosis 32±14 years) were included. The diagnosis of CeD was confirmed by gastroscopy and duodenal biopsy in 97% of cases, and the most common histological lesion was Marsh 3. Overall, there were no significant differences in the duration of IBD (median 11±8 years vs 9±8 years; p=0.81), IBD extension (UC (E1/E2/E3): 6 (20.7%)/14 (48.3%)/9 (31%) vs 19 (29.2%)/22 (33.8%)/24 (36.9%); p=0.39); CD (L1/L2/L3/L4): 17 (56.7%)/3 (10%)/8 (26.7%)/2 (6.7%) vs 27 (45%)/6 (10%)/23 (38.3%)/4 (6.4%); p=0.71), extra-intestinal manifestations (10 (15,2%) vs 20 (12,8%); p=0.96) and other autoimmune diseases (8 (12%) vs 16 (12.1%); p=1) between celiac and non-celiac IBD, respectively. In terms of disease outcome, no differences were found either globally or by IBD subtype in terms of perianal disease, use of mesalamine, exposure to immunomodulators, receipt of biologic agents, need for IBD surgery, and development of neoplasm during follow-up (Table 1). There was no mortality in any of the cohorts. Conclusion No significant differences in disease outcome were observed in patients with a concurrent diagnosis of CeD and IBD compared with non-celiac IBD patients. In our large multicenter cohort of patients with celiac IBD and IBD controls, coexisting CeD did not show an impact on the natural history of IBD.

P708 Multiple Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes in Inflammatory Bowel Disease: A Real-World Effectiveness Analysis in a National U.S. Cohort

Abstract Background Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD. Methods We conducted a retrospective cohort study of IBD patients on maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. Cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from originator to one biosimilar, or Double Switch (DS)-switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate (MV) logistic regression models adjusting for patient and non-patient factors. Results 789 patients (487 CD, 298 UC) on maintenance IFX originator were identified. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In MV logistic regression including age, race, gender, medication, comorbidity and VA priority status, no significant differences in flares at 12 months was observed between DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82). Conclusion In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, DS was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.

P1015 Subcutaneous infliximab effectively manages clinical outcomes of Inflammatory Bowel Disease independently of various confounding factors

Abstract Background Since its approval, many inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but the association of various confounding factors with clinical outcomes is still elusive. Methods The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 database analysis, three studies from France and the United Kingdom1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) <5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) <3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. After adjustment with inverse probability of treatment weights (IPTW), the association of various parameters on clinical outcomes was assessed with marginal structural models (MSMs), by comparing the estimated marginal means (EMMs) of remission rates at 6M between patients in each subgroup. Results The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching to SC IFX with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. The overall clinical remission and persistence rates at 6M after switching were 84.7% and 94.5%, respectively. Pre-switch IV IFX regimens, immunomodulator (IMM) use, age, baseline fecal calprotectin (FC) level, or baseline C-reactive protein (CRP) level were not associated with persistence. Persistence rate was >90% regardless of body mass index (BMI), although it was higher for patients <25 kg/m2 BMI (98.1%). Assessment with MSMs indicated that the clinical remission rate of CD, but not UC, was expected to be significantly lower only if patients were treated with escalated IV IFX before switching rather than standard 5 mg/kg Q8W regimen (p=0.01; Table 1). No association with high BMI, IMM use, age, ≥150 μg/g FC, and ≥5 mg/L CRP was found in both CD and UC (Table 1). Perianal disease was not associated with CD remission either. Conclusion The ASSEMBLE-1 results confirm that switching from IV to SC IFX is well accepted and effectively manages the clinical outcomes of the disease regardless of various confounding factors in IBD patients. However, further studies are warranted to explore the association of pre-switch IV IFX regimens with clinical outcomes. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.

P286 Variation of outcomes in inflammatory bowel disease at ten Australasian centres - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Inflammatory bowel disease (IBD) is a global health issue with Australia having amongst the highest prevalence rates worldwide. Our study examined the quality, safety and equity of care amongst ten Australasian centres using Crohn’s Colitis Care electronic management record. The aim was to describe current care delivery at each centre for a range of performance indicators to provide a baseline from which to engage in a regional care quality benchmarking initiative Methods Deidentified data prospectively entered by clinicians during routine clinical practice throughout 2022 were retrospectively analysed. Only centres with >100 eligible people with IBD and an assessment during the trial period were included. Sites from Australia and New Zealand were a mixture of public and private IBD referral centres Results The cohort included 7172 people with IBD from 10 centres; 58.6% with Crohn’s disease (CD), 39.1% ulcerative colitis (UC) and 2.3% IBD-unclassified (IBDU). Mean age was 44.3 (SD +/- 18.0) with an even gender balance (50.7% female). The number of people with IBD per centre ranged from 201 to 2151 (median 566). In the total cohort, 38.3% were currently on advanced IBD therapy (biologics or new small molecules), with centre variation from 30.8% to 43.5% (p<0.001). Of those on advanced therapy, 42% were on dose escalated therapy which varied between centres substantially from 18% to 64%. Current steroid use ranged from 0.3% to 6.1% (median 1.6%; p<0.001). Documented IBD surgical rates varied from 0.1% to 7.2% (median 2.0; p<0.001). IBD admission rates ranged from 0.1% to 13.6% (median 1.2; p<0.001) while current smokers comprised 1.7% to 12.5% (p<0.001) of the cohort with a mean of 6.0% across all ten centres. A total of 3,379 faecal calprotectin’s (FCP) with an overall remission rate (< 250μg/g) of 71% varying from 63.4% to 83.1% (median 69.1; p=0.001); 2,616 lower endoscopies were performed with an observed remission rate of 56%; this varied between sites from 0% to 69%. Recorded Influenza vaccination rates varied from 6.3% to 54.4% (median 19.8) and Covid vaccination rates from 14% to 78.5% (median 43.4). Skin care check completion rates ranged from 16.3% to 32.3% (median 22.9). The centre with the highest documented healthcare maintenance completion rate across all three domains was private. Conclusion Despite advances in treatment and much literature addressing care guidelines and targets, significant disparity in care documentation and outcomes remains for people with IBD in routine care. CCCare as an IBD-specific EMR supports easy, serial examination of these measures at scale and is therefore a useful tool to measure and drive efforts to improve these deficiencies and reduce unwarranted care variation

P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort. Methods We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE. Results A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml). Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001). Conclusion Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.

P1179 Long-term impact of COVID-19 on the disease course of IBD: a meta-analysis

Abstract Background Viral infections have been implicated in the exacerbation of immune-mediated inflammatory diseases like inflammatory bowel disease (IBD). The COVID-19 pandemic, therefore, sparked interest in whether infection with the virus has an adverse effect on the course of IBD. Since the existing evidence is conflicting and limited by a small sample size, we performed the very first meta-analysis to study the long-term impact of SARS-CoV-2 infection on the disease course of IBD. Methods We performed a systematic literature search in MEDLINE and EMBASE for studies that explored the risk of adverse IBD outcomes following a SARS-CoV-2 infection. We used the random effects model meta-analysis to calculate the pooled hazard ratio for the risk of IBD flares following the acute phase of COVID-19. Subgroup meta-analysis was carried out for the risk of the outcomes by IBD subtype. Meta-regression was carried out for sex and duration of follow-up. The ROBINS-E tool for observational studies was used to assess the quality of the studies. Results A total of 5 studies were included in the meta-analysis. The studies were based on cohorts from Denmark, Italy, the US, and a cohort from a consortium of the EU comprising a total of 34977 SARS-CoV-2 positive IBD patients and 53270 IBD patients without the infection as controls. Two of the studies had a high risk of bias according to the quality assessment tool. The meta-analysis did not show an increased risk of IBD-related outcomes in IBD patients who contracted a SARS-CoV-2 infection compared to those who did not (HR: 1.0514, CI: 0.7547- 1.4646, p= 0.7671). There was substantial heterogeneity between the included studies (91%, p<0.01). There was no significant difference between CD and UC patients in terms of disease flare (CD- HR: 0.9134, CI: 0.8163-1.0220; UC- HR: 0.8257, CI: 0.7549-0.9032). Neither sex nor the duration of follow-up was a predictor of the overall effect size. Conclusion In this group of patients, SARS-CoV-2 infection does not increase the risk of adverse outcomes related to IBD. High-quality studies with longer follow-up duration are required to understand the long-term impact of SARS-CoV-2 infection on IBD prognosis.

P337 Proactive therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome and persistence of treatment

Abstract Background Anti-TNF drugs have proven effective in managing Inflammatory Bowel Disease (IBD), but a significant percentage of patients exhibit primary or secondary non-response. Therapeutic drug monitoring (TDM) is a valuable tool for optimizing patient management. HLA-DQA1*05 gene has been investigated as a potential marker for immunogenicity and loss of response to anti-TNF therapy.This prospective, multicentric study aimed to assess the clinical impact of determining Adalimumab (ADA) levels and anti-adalimumab antibodies (Abs) in IBD patients and the influence of the HLA-DQA1*05 allele on the response and maintenance of ADA treatment over a 24-month follow-up. Methods Patients initiating ADA treatment between October 2020 and October 2022 were enrolled. Demographic data and IBD characteristics were recorded. Clinical Activity Index, C reactive protein (CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was utilized to assess correlations between ADA levels and disease activity. Results We included 170 (age 42±17 years, 54% female) IBD patients (74% Crohn`s Disease, 24% Ulcerative Colitis and 2% Indeterminate colitis) who started ADA (85% naïve to anti-TNF). At baseline, 80% had an active disease (GPA=1); CRP and FC were 10.72 ±17.85 mg/L and 568 ±775 µg/g; PRO at baseline was 63±8.6. HLA was determined in 167 patients, of whom 71 (42%) were HLA-DQA1*05 positives. Median follow up was 17 months. No correlation between HLA and drug levels or Abs was founded. ADA levels at the end of induction was correlated with ADA levels during follow up. ADA serum concentration >7 µg/mL at weeks 4 and 10 correlated with improved clinical response at corresponding time points (p<0.001). Patients with ADA levels >7 µg/mL at week 10 demonstrated better disease control at 12 months. 41 patients stopped ADA. It was associated with active disease, low ADA levels, and adverse clinical and laboratory markers. HLA-DQA1*05 positivity did not correlate with adverse reactions or Abs during the observational period. A significative improvement in PROs in patients who started treatment with ADAL (62.73 at baseline and 69.42 at week 30) (p<0.001) was observed. Conclusion Early Drug level monitoring of Adalimumab may improve the management of IBD patients. PCR, CF and GPA at week 10 may predict treatment failure. ADA levels >7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.

Inpatient outcomes of inflammatory bowel disease in hospitalized patients with COVID-19: analysis of a nationally representative sample

Purpose To compare the risks of adverse outcomes, including mortality, gastrointestinal bleeding, and venous thromboembolism, between COVID-19 patients with inflammatory bowel disease (IBD) and those without IBD. Methods We analyzed data from the National Inpatient Sample between January and December 2020. The study included adult patients with Crohn’s disease (CD) and ulcerative colitis (UC) who contracted COVID-19. Inpatient outcomes were compared between the IBD and non-IBD COVID-19 cohorts. Results Out of 1,050,045 COVID-19 hospitalizations, 0.28% had CD (2954 patients) and 0.26% had UC (2794 patients). After adjusting for confounding factors, UC patients had a significantly higher risk of deep vein thrombosis compared to non-IBD patients, with an adjusted odds ratio (aOR) of 2.55 (P < 0.001). However, CD patients did not show a significant association with deep vein thrombosis (aOR 1.29, P = 0.329). There were no significant associations between IBD patients (both UC and CD) and pulmonary embolism, nonvariceal gastrointestinal bleeding, or in-hospital mortality. UC patients had a longer average hospital stay (8.25 days) compared to non-IBD patients (adjusted mean difference 0.89, P = 0.007). Healthcare resource utilization was similar among the three groups. Conclusion Our national study on COVID-19 hospitalizations indicates that patients with IBD have comparable rates of gastrointestinal bleeding, pulmonary embolism, and mortality as those without IBD. However, patients with UC hospitalized with COVID-19 have a higher risk of deep vein thrombosis than COVID-19 patients hospitalized without UC. Further research is needed to better understand the relationship between COVID-19 and IBD.

Co-Administration of Proton Pump Inhibitors May Negatively Affect the Outcome in Inflammatory Bowel Disease Treated with Vedolizumab.

Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided.

Treatment trajectories and outcomes in inflammatory bowel disease: a tertiary single-centre experience.

There is an increasing diversification in the treatment landscape for inflammatory bowel diseases (IBD) leading to therapeutic challenges that can only incompletely be covered by prospective randomized double-blind trials. Real-world observations are therefore an important tool to provide insights into therapeutic strategies. To describe the real-world treatment algorithms in an IBD referral centre. Single-centre retrospective cohort study. We retrospectively analysed prospectively collected data on treatment sequences and outcomes from 502 patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with infliximab, adalimumab, vedolizumab or ustekinumab at a large German tertiary referral centre. Treatment decisions correlated to baseline patient characteristics. Over time, infliximab continued to be the preferred first-line option in CD and UC, although ustekinumab and vedolizumab, respectively, became increasingly important choices. Remission rates decreased with the advancement of therapy lines. We provide insights into the evolution of tertiary centre real-world treatment sequences that might - together with other observations - help to guide the selection of therapies in IBD. Our data also strongly underscore the unmet need for biomarkers supporting treatment decisions. None.

Sex and age differences in inflammatory bowel disease patients; a nationwide study based on Iranian Registry of Crohn's and Colitis (IRCC).

Despite the rising prevalence of Inflammatory Bowel Disease (IBD), age and sex differences in its outcomes remain understudied. We investigated age and sex differences in IBD patients using a nationwide study in Iran, the Iranian Registry of Crohn's and Colitis (IRCC). The IRCC is a national registry that gathered information on adult IBD patients since 2017. The collected data included demographic information, medication history, disease activity, comorbidities, diagnosis age, prognosis, the extent of ulcerative colitis (UC), Crohn's disease (CD) location, and extraintestinal manifestations. The statistical methods included the independent Student's t-test, Chi-square test, and binary logistic regression, using R version 4.2.2. Among the 9,392 IBD patients, 7,496 (3,600 females) and 1,896 (808 females) had UC and CD, respectively. Sex difference showed higher odds of active disease in the past six months in male CD patients (OR 1.24 [95%CI 1.03, 1.49]) vs. females, but in male UC patients, the OR was 0.85 [0.78, 0.93]. Severe disease was less likely in CD patients aged 19-59 and >60 vs. <18. Similarly, UC patients <18 had lower odds of severe disease vs. those aged 19-59 and >60. This study emphasizes the importance of understanding age and sex differences in IBD outcomes. These findings contribute to the ongoing global discussion on IBD management and facilitate the development of targeted interventions and personalized care.

Early infliximab trough levels in paediatric IBD patients predict sustained remission.

Exposure-response studies have shown that higher infliximab concentrations are associated with better outcomes in inflammatory bowel disease. There is little agreement about the optimal time to measure infliximab levels in children. We aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission. The secondary aim was to define target trough levels at weeks 6 and 14. We used routinely collected electronic healthcare data of 70 anti-tumour necrosis factor naïve children with inflammatory bowel disease treated with a standard infliximab induction- and variable maintenance scheme. Trough levels and blood and faecal markers for disease activity were measured before every infliximab administration. Sustained remission was defined as the absence of symptoms and low inflammatory markers between weeks 26 and 52 after the start of infliximab therapy. Optimal infliximab levels at weeks 6 and 14 were determined using the receiver operating characteristic curve. The median infliximab level at week 6 was not significantly higher in children who achieved sustained remission compared to those who did not (16.9 mg/L versus 12.0 mg/L; p = 0.058) but the median infliximab level at week 14 was significantly higher in those with sustained remission (7.7 mg/L versus 3.8 mg/L; p = 0.006). The area under the receiver operating characteristics curves at weeks 6 and 14 to predict sustained remission was 0.67 (95% CI 0.51-0.83) and 0.75 (95% CI 0.60-0.90), respectively. Target trough levels at weeks 6 and 14 were ⩾13.2 and ⩾6.9 mg/L, respectively. An infliximab measurement at week 14 with a target through level ⩾6.9 mg/L best predicted sustained remission.

Monoclonal Antibody Against Mature Interleukin-18 Ameliorates Colitis in Mice and Improves Epithelial Barrier Function.

Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD. The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed. Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression. Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.

Gastrointestinal microbiota-directed nutritional and therapeutic interventions for inflammatory bowel disease: opportunities and challenges.

Evidence-based research has confirmed the role of gastrointestinal microbiota in regulating intestinal inflammation. These data have generated interest in developing microbiota-based therapies for the prevention and management of inflammatory bowel disease (IBD). Despite in-depth understanding of the etiology of IBD, it currently lacks a cure and requires ongoing management. Accumulating data suggest that an aberrant gastrointestinal microbiome, often referred to as dysbiosis, is a significant environmental instigator of IBD. Novel microbiome-targeted interventions including prebiotics, probiotics, fecal microbiota transplant, and small molecule microbiome modulators are being evaluated as therapeutic interventions to attenuate intestinal inflammation by restoring a healthy microbiota composition and function. In this review, the effectiveness and challenges of microbiome-centered interventions that have the potential to alleviate intestinal inflammation and improve clinical outcomes of IBD are explored.

Differential Manifestations of Inflammatory Bowel Disease Based on Race and Immigration Status

Background and AimsThe prevalence of inflammatory bowel disease (IBD) is increasing globally. In this context, identifying risk factors for severe disease is important. We examined how race/ethnicity and immigration status influence IBD manifestations, treatments, and outcomes in a diverse, tertiary-care safety-net hospital. MethodsWe conducted a single-center retrospective review of all IBD inpatients and outpatients treated from 1997-2017. Using logistic regression modeling, we compared disease onset, treatment, and outcomes by race (White, Black, Hispanic, Asian) and immigration status (US-born vs. foreign-born). ResultsA total of 577 patients were identified, of which 29.8% were White, 27.4% Hispanic, 21.7% Black, and 13.0% Asian. Compared to Whites, Asians were more likely to be male (OR 2.63, 95% CI: 1.45, 5.00), whereas Blacks were more likely to be diagnosed with Crohn’s disease (CD) (OR 1.75, 95% CI: 1.10, 2.77) and more likely to undergo IBD-related intestinal resection (OR 2.49, 95% CI: 1.40, 4.50). Compared to US-born patients, foreign-born patients were more likely to be diagnosed with UC (OR 1.77, 95% CI: 1.04, 3.02). They were also less likely to be diagnosed before 16 years of age (OR 0.19, 95% CI: 0.08, 0.41), to have undergone intestinal resections (OR 0.39, 95% CI: 0.19, 0.83), to have received biologics (OR 0.43, 95% CI: 0.25, 0.76), or to have had dermatologic manifestations (OR 0.12, 95% CI: 0.03, 0.41). ConclusionsIBD phenotype varies by race, although foreign-born patients of all races show evidence of later onset and milder disease. These findings may aid in disease prognostication and clinical management and furthermore may provide insight into intrinsic and environmental influences on IBD pathogenesis.