Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers.

INTRODUCTION: Approximately 50% of Crohn's disease (CD) patients develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of CD patients. METHODS: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 CD patients and 10 non-inflammatory bowel disease (IBD) controls. Macroscopically, unaffected, fibrostenotic and inflamed ileum was collected and analysed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed via a Masson's Trichrome staining. Eosinophil and fibroblast co-localization was assessed through immunohistochemistry. RESULTS: The Masson's Trichrome staining confirmed augmented collagen deposition in both the fibrotic as the inflamed region, though with a significant increased collagen deposition in fibrotic compared to inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells and monocytes were identified in fibrotic and inflamed CD ileum compared to unaffected ileum of CD patients as non-IBD controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased Eosinophil Cationic Protein (ECP) protein expression in inflamed deeper layers. Lastly, no differences in eosinophil and fibroblast co-localization was observed between the different regions. CONCLUSION: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of CD patients. Immunologic, proteomic and histological data suggest inflammation and fibrosis are intertwined, with large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.

Efficacy and Safety of Ustekinumab for Chronic Pouchitis: A Prospective Open-label Multicenter Study.

BACKGROUND & AIMS: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients. METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI. RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001). CONCLUSION: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).

Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn's Disease: A Belgian Multicentric Cohort Study.

BACKGROUND: As real-world data on risankizumab in patients with moderate to severe Crohn's disease (CD) are scarce, we evaluated its effectiveness and safety in multirefractory Belgian patients. METHODS: Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. Clinical remission and response were defined using the 2-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score with ≥50%. Both effectiveness end points were evaluated at week 24 and/or 52, while surgery-free survival and safety were assessed throughout follow-up. RESULTS: A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included. At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively. At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks. Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively). During a median follow-up of 68.3 weeks, 18.8% (13 of 69) of patients discontinued risankizumab, and 20.3% (14 of 69) of patients underwent CD-related intestinal resections. The estimated surgery-free survival at week 52 was 75.2%. No new safety issues were observed. CONCLUSIONS: In this real-world cohort of multirefractory CD patients, risankizumab was effective in inducing both clinical remission and endoscopic response. Risankizumab was well tolerated with no safety issues.

In this real-world study of multirefractory Crohn's disease patients, risankizumab was effective, with 58.2% and 27.3% achieving steroid-free clinical response and remission, respectively, at week 52. Surgery-free survival at week 52 was 75.2%, and no new safety concerns arose.

The assessment of segmental healing by the Modified Mayo Endoscopic Score (MMES) complements the prediction of long-term clinical outcomes in patients with ulcerative colitis.

BACKGROUND AND AIMS: Current endoscopic scoring systems for ulcerative colitis (UC) do not consider the extent of mucosal inflammation. The modified Mayo endoscopic score (MMES) was developed to detect segmental endoscopic improvement. We evaluated the ability of the MMES to predict long-term clinical outcomes and compared it to the widely used Mayo endoscopic subscore (MES). METHODS: Consecutive patients with moderate to severe UC starting biological therapy were enrolled between January 2014 and September 2017 in this prospective observational study. A clinical and endoscopic evaluation was performed at baseline and at week 8/14. A modified Mayo score was used to grade clinical activity, MES and MMES were used to evaluate endoscopic activity. Patients were divided into 3 groups according to the evolution of endoscopic activity, namely endoscopic improvement (MES ≤ 1), segmental endoscopic response only (MES > 1, but decrease in MMES ≥ 30%) or no endoscopic response (all others). Over the follow-up period clinical relapse-, discontinuation- and colectomy-free survival were assessed. RESULTS: A total of 150 patients were included (48% female, median age 42 years, median disease duration 7 years) with a median follow-up of 61 months. We identified 69 patients with endoscopic improvement, 27 with segmental endoscopic response and 54 without endoscopic response. Patients with segmental endoscopic response showed intermediate long-term clinical outcomes as compared to the other two groups (log rank p = 0.003 for clinical relapse-, and p < 0.001 for both discontinuation- and colectomy-free survival). CONCLUSIONS: The MMES exhibited a benefit in predicting long-term outcome in UC even though endoscopic improvement remains the strongest predictor.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

The Role of MRI in the Diagnosis of Spinal Cord Tumors.

Spinal cord tumors are uncommon, and its multiple representatives not always have pathognomonic characteristics, which poses a challenge for both patients and caring physicians. The radiologist performs an important role in recognizing these tumors, as well as in differentiating between neoplastic and non-neoplastic processes, supporting clinical and surgical decision-making in patients with spinal cord injury. Magnetic Resonance Imaging (MRI) assessment, paired with a deep understanding of the various patterns of cord involvement allied to detailed clinical data can provide a diagnosis or significantly limit the differential diagnosis in most cases. In this article, we aim to review the most common and noteworthy intramedullary and extramedullary spinal tumors, as well as some other tumoral mimics, with an emphasis on their MRI morphologic characteristics.

Effect of anastomotic configuration on Crohn's disease recurrence after primary ileocolic resection: a comparative monocentric study of end-to-end versus side-to-side anastomosis.

There is ongoing debate whether the type of anastomosis following intestinal resection for Crohn's disease (CD) can impact on complications and postoperative recurrence. The aim of the present study is to describe the outcomes of side-to-side (S-S) vs end-to-end (E-E) anastomosis after ileocecal resection for CD. A retrospective comparative study was conducted in consecutive CD patients who underwent primary ileocecal resection between 2005 and 2013. All patients underwent colonoscopy 6 months postoperatively to assess endoscopic recurrence, defined as Rutgeerts' score (RS) ≥ i2. Surgical recurrence implied reoperation due to CD activity at the anastomotic site. Modified surgical recurrence was defined as the need for reoperation or balloon-dilation. Perioperative factors related to recurrence were evaluated. Of the 127 patients included, 51 (40.2%) received an E-E anastomosis. Median follow-up was longer in the E-E group (8.62 vs 13.68 years). Apart from the microscopic resection margins, patient, disease and surgical characteristics were similar between both groups. Anastomotic complications were comparable (S-S 5.3% vs E-E 5.8%, p = 1.00)0. Postoperatively, biologicals were used in 55.3% and 62.7% (p = 0.47) in S-S and E-E patients, respectively. Endoscopic recurrence did not differ between S-S and E-E patients (78.9 vs 72.9%, p = 0.37), with no significant difference in RS values between both groups (p = 0.87). Throughout follow-up, a higher surgical (p = 0.04) and modified surgical recurrence (p = 0.002) rate was observed in the E-E anastomosis group. Type of anastomosis was an independent risk factor for modified surgical recurrence. The type of anastomosis did not influence endoscopic recurrence and immediate postoperative disease complications. However, the wide diameter and the morphologic characteristic of the stapled S-S anastomosis resulted in a significant reduced risk for surgical and endoscopic reintervention on the long term.

Position statement on the management of the immune checkpoint inhibitor-induced colitis via multidisciplinary modified Delphi consensus.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has shown increased overall survival in a wide range of cancer types with the associated risk of developing severe immune-mediated adverse events, commonly involving the gastrointestinal tract. AIM: The aim of this position statement is to provide an updated practice advice to the gastroenterologists and oncologists on the diagnosis and management of ICI-induced gastrointestinal toxicity. METHODOLOGY: The evidence reviewed in this paper includes a comprehensive search strategy of English language publications. Consensus was reached using a three-round modified Delphi methodology and approved by the members of the Belgian Inflammatory Bowel Disease Research and Development Group (BIRD), Belgian Society of Medical Oncology (BSMO), Belgian group of Digestive Oncology (BGDO), and Belgian Respiratory Society (BeRS). CONCLUSIONS: The management of ICI-induced colitis requires an early multidisciplinary approach. A broad initial assessment is necessary (clinical presentation, laboratory markers, endoscopic and histologic examination) to confirm the diagnosis. Criteria for hospitalisation, management of ICIs, and initial endoscopic assessment are proposed. Even if corticosteroids are still considered the first-line therapy, biologics are recommended as an escalation therapy and as early treatment in patients with high-risk endoscopic findings.

Review article: Putting some muscle into sarcopenia-the pathogenesis, assessment and clinical impact of muscle loss in patients with inflammatory bowel disease.

BACKGROUND: Sarcopenia, a loss of skeletal muscle mass or function, affects up to 50% of patients with inflammatory bowel disease (IBD) and is associated with poor clinical outcomes including increased hospitalizations, need for surgery and post-operative complications. Despite the high prevalence and clinical significance of sarcopenia in patients with IBD, few patients undergo routine muscle evaluation. AIM: The goal of this study was to review the mechanisms of sarcopenia in patients with IBD and understand novel modalities to assess and treat impaired muscle mass or function. METHODS: Pubmed and Cochrane databases were searched including articles published up to February 2023 utilizing the following keywords: "inflammatory bowel disease", "IBD", "Crohn's disease", "ulcerative colitis", "sarcopenia", "myosteatosis", "muscle health", and "frailty". RESULTS: The pathogenesis of sarcopenia in IBD is not well defined, however, there is evidence supporting the role of malabsorption, reduced protein intake, chronic inflammation, dysbiosis, decreased physical activity, medication effects and hormone signaling from visceral adiposity. Traditional sarcopenia assessment techniques include direct measurements on cross sectional imaging. However, given the time, cost and radiation exposure associated with cross sectional imaging, new bedside tools are now available to estimate muscle mass, including assessment of grip strength, mid upper arm circumference and body composition utilizing bioelectrical impedance analysis. In addition, novel biomarkers for assessing muscle mass and techniques utilizing point of care ultrasound have been proposed to make sarcopenia evaluation more streamlined in the IBD clinic. CONCLUSION: Sarcopenia is associated with poor clinical outcomes independent of IBD activity and therefore muscle health should be assessed in all IBD patients at routine intervals. Future studies to better our understanding of the pathophysiology as well as most effective management of sarcopenia in IBD will help guide clinical care and reduce disease related complications.

SARS-CoV-2 infection and COVID19 vaccination across eight immune-mediated inflammatory disorders: A prospective, real-life Belgian cohort study - the BELCOMID study.

Background: The risks and impact of COVID19 disease and vaccination in patients with Immune Mediated Inflammatory Diseases (IMID) remain incompletely understood. IMID patients and particularly patients receiving immunosuppressive treatment were excluded from the original, registrational phase-3 COVID19 vaccination efficacy and safety trials. Real-world observational data can help to fill this gap in knowledge. The BELCOMID study aims to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Methods: A multidisciplinary, prospective, observational cohort study was set up. Consecutive patients with IMIDs of the gut, joints and skin followed at two high-volume referral centers were invited. Both patients under conventional treatment or targeted immune modulating therapies were included. Patient data and serological samples were collected at 3 predefined periods (before COVID19 vaccination, before booster vaccination, after booster vaccination). Primary endpoints were positive PCR-test and SARS-CoV-2 serology reflecting previous SARS-CoV-2 infection or vaccination. Associations with IMID treatment modality and IMID disease activity were assessed. Results of the first two inclusion periods (before booster vaccination) are reported. Results: At the first inclusion period data was assessed of 2165 IMID-patients before COVID19 vaccination. At the second inclusion period, data of 2065 patients was collected of whom 1547 had received complete baseline COVID19 vaccination and 222 were partially vaccinated. SARS-CoV-2 infection rate remained low in both groups. No significant increase in IMID flare-up rate was noted in patients with prior SARS-CoV-2 infection. Multiple logistic regression analyses did not show a significant influence of IMID-treatment modality or IMID activity on SARS-CoV-2 infection risk (based on PCR positivity or N-serology). Patients treated with conventional immunomodulators, systemic steroids, and patients on advanced therapies such as biologics or small molecules, had reduced S-antibody seroconversion. S-antibody response was also lower in patients without prior SARS-CoV-2 infection and in active smokers. A subset of patients (4.1%) had no S- nor N-antibody seroconversion following complete baseline vaccination. Conclusion: The BELCOMID study results confirm the benign course of COVID19 infection and vaccination in a large real-life IMID-population. However, our results underscore the need for repeated vaccination and smoking cessation in patients with IMIDs treated with immune-modulating therapies or systemic steroids during the pandemic.

Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD.

OBJECTIVE: To infer potential mechanisms driving disease subtypes among patients with inflammatory bowel disease (IBD), we profiled the transcriptome of purified circulating monocytes and CD4 T-cells. DESIGN: RNA extracted from purified monocytes and CD4 T-cells derived from the peripheral blood of 125 endoscopically active patients with IBD was sequenced using Illumina HiSeq 4000NGS. We used complementary supervised and unsupervised analytical methods to infer gene expression signatures associated with demographic/clinical features. Expression differences and specificity were validated by comparison with publicly available single cell datasets, tissue-specific expression and meta-analyses. Drug target information, druggability and adverse reaction records were used to prioritise disease subtype-specific therapeutic targets. RESULTS: Unsupervised/supervised methods identified significant differences in the expression profiles of CD4 T-cells between patients with ileal Crohn's disease (CD) and ulcerative colitis (UC). Following a pathway-based classification (Area Under Receiver Operating Characteristic - AUROC=86%) between ileal-CD and UC patients, we identified MAPK and FOXO pathways to be downregulated in UC. Coexpression module/regulatory network analysis using systems-biology approaches revealed mediatory core transcription factors. We independently confirmed that a subset of the disease location-associated signature is characterised by T-cell-specific and location-specific expression. Integration of drug-target information resulted in the discovery of several new (BCL6, GPR183, TNFAIP3) and repurposable drug targets (TUBB2A, PRKCQ) for ileal CD as well as novel targets (NAPEPLD, SLC35A1) for UC. CONCLUSIONS: Transcriptomic profiling of circulating CD4 T-cells in patients with IBD demonstrated marked molecular differences between the IBD-spectrum extremities (UC and predominantly ileal CD, sandwiching colonic CD), which could help in prioritising particular drug targets for IBD subtypes.

Screening Failure in a Large Clinical Trial Centre for Inflammatory Bowel Diseases: Rates, Causes, and Outcomes.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) sometimes require investigational medicinal therapy in a clinical trial. Before enrollment, patients must meet strict eligibility criteria, hampering recruitment rates. We investigated the rates, causes, and outcomes of screening failure (SF) in a tertiary IBD center. METHODS: We reviewed all IBD patients screened for sponsored multicenter phase 1-3 induction studies with available global SF rates between January 2008 and March 2021. We compared our SF rates with the global SF rates. Causes of SF were categorized into disease activity, hematology, chemistry, microbiology, protocol violation, and withdrawal of consent. Patient outcomes were categorized into rescreening for the same trial, screening for another trial, (re)introduction of commercially available therapy, surgery, or watchful waiting. RESULTS: During the study period, 642 local screenings were performed as part of 53 studies. We identified an overall SF rate of 17.1%, compared with 39.2% in the global study population (P < .00001). Causes of SF at our center included ineligible disease activity (36.4%), microbiology (25.5%), protocol violation (16.4%), withdrawal of consent (9.1%), chemistry (6.4%) and hematology (6.4%). Thirty SFs could have been avoided by prescreening that was more thorough. After SF, 34 patients were rescreened for the same trial, 17 screened for another trial, 38 initiated approved therapy, 9 were referred for surgery, and 12 did not receive further therapy. CONCLUSIONS: A significant proportion of IBD patients consenting to clinical trials fail their screening. Main causes of SF are ineligible disease activity and abnormal finding on microbiology. Approximately one-fourth of SFs could have been avoided by prescreening that was more thorough.

What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study.

BACKGROUND AND AIMS: As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients' preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. METHODS: This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. RESULTS: IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medication's long-term effects. Furthermore, participants extensively discussed the mental impact of IBD and their need for more psychological guidance, support, and improved information and communication with healthcare workers regarding their disease and emotional wellbeing. The following five characteristics were identified during the attribute grading as most important: prevent surgery, long-term clinical remission, improved quality of life [QoL], occurrence of urgency and improved labour rate. CONCLUSIONS: This study suggests that IBD drug development and treatment decision-making are needed to improve IBD symptoms and adverse events that significantly impact IBD patients' QoL. Furthermore, this study underlines patients' need for a shared decision-making process in which their desired treatment outcomes and uncertainties are explicitly discussed and considered.

Adalimumab versus ustekinumab as first-line biological in moderate-to-severe Crohn's disease: real-life cohort from a tertiary referral center.

BACKGROUND: Therapeutic options for Crohn's disease are growing, making the choice of first-line therapy relevant. Both adalimumab and ustekinumab are effective in moderate-to-severe Crohn's disease. The Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year trial suggested no difference in clinical or endoscopic remission at week 52 in biological-naive Crohn's disease patients. We explored if results withstand in the real world. METHODS: We included bio-naive Crohn's disease patients starting adalimumab or ustekinumab between 2017 and 2020. Patients had endoscopy-proven moderate-to-severe disease [Simple Endoscopic Score for Crohn's disease (SES-CD) ≥3]. Clinical remission was defined as Harvey Bradshaw Index (HBI) <5 or physician global assessment. Endoscopic remission (SES-CD <3) and improvement (≥50% reduction in SES-CD from baseline) were assessed at W26-52. Propensity score matching was used. RESULTS: A total of 68 biological-naive Crohn's disease patients were included (32 adalimumab and 32 ustekinumab) and followed for median of (IQR) 60 (33-104) weeks. Patients had significantly higher odds of achieving endoscopic remission with adalimumab than ustekinumab [adjusted odds ratio (aOR), 2.73; confidence interval (CI), 1.12-7.36; P = 0.03]. Also, more adalimumab-treated patients achieved endoscopic response, clinical remission at week 26 and 52 (aOR, 2.24; CI, 0.94-5.71; P = 0.07; aOR, 1.26; CI, 0.36-4.51; P = 0.72; aOR, 1.58; CI, 0.54-4.88; P = 0.41, respectively). Treatment persistence was not different between groups (P = 0.44). The number of adverse events was similar. CONCLUSION: In a real-world cohort of biological-naive Crohn's disease patients, adalimumab was superior to ustekinumab in achieving endoscopic remission. No differences in clinical remission at W26-52 or treatment persistence were observed. Both adalimumab and ustekinumab remain good options as first-line biologicals in moderate-to-severe Crohn's disease.

Performance measures for colonoscopy in inflammatory bowel disease patients: European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy (ESGE) presents a short list of performance measures for colonoscopy in inflammatory bowel disease (IBD) patients. Current performance measures for colonoscopy mainly focus on detecting (pre)malignant lesions. However, these performance measures are not relevant for all colonoscopy indications in IBD patients. Therefore, our aim was to provide endoscopy services across Europe and other interested countries with a tool for quality monitoring and improvement in IBD colonoscopy. Eight key performance measures and one minor performance measure were recommended for measurement and evaluation in daily endoscopy practice.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

Real-world Endoscopic and Histological Outcomes Are Correlated with Ustekinumab Exposure in Patients with Ulcerative Colitis.

BACKGROUND: Histo-endoscopic outcomes are being proposed as new treatment targets in ulcerative colitis [UC]. Little is known about the pharmacokinetic-pharmacodynnamic [PK-PD] relationship of ustekinumab [UST] in UC patients or whether serum UST concentrations reflect tissue drug exposure. We aimed to study UST serum concentrations and their relation to tissue exposure and drug effectiveness in a real-world setting. METHODS: A total of 42 UC patients starting UST were prospectively followed by clinical, endoscopic and histological assessments at Week 16. Histological remission was defined as Nancy Histology Index of 0. Analogous to the UNIFI programme, histo-endoscopic mucosal improvement was defined as a combination of histological improvement [Geboes ≤3.1] and endoscopic improvement [MES ≤1]. Paired trough serum samples and colonic mucosal biopsies were collected for UST levels measurement. RESULTS: After 16 weeks [IQR 15.8-16.4] of therapy, histological remission and histo-endoscopic mucosal improvement were observed in 19 [45%] and 18 [43%] patients, respectively. Patients who achieved these outcomes had higher serum UST levels than those who did not. Patients with shorter disease duration and clinical response at Week 8 had higher odds to achieve histological remission. UST concentrations from paired serum and biopsy samples revealed a strong positive correlation [r = 0.88, p < 0.001], in both inflamed and uninflamed tissue. CONCLUSIONS: In this real-world cohort of refractory UC patients initiating UST, more than a third of the patients achieved histological remission. A drug exposure-response relationship was observed for histo-endoscopic outcomes, with no added value of measuring tissue exposure given the strong correlation with serum exposure.

Safety of sequential biological therapy in inflammatory bowel disease: results from a tertiary referral centre.

BACKGROUND: Biologicals represent the cornerstone of treatment for moderate-to-severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events. AIM: To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals. METHODS: We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for. RESULTS: In total, 1575 patients were included with a median (interquartile range) follow-up of 10 (6-16) years and a duration of biological therapy of 71 (39-112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post-biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78-4.93], p < 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37-4.34], p = 0.002), female gender (1.25 [1.04-1.51], p = 0.02), and prior serious infections in the pre-biological setting (1.42 [1.03-1.96], p = 0.03). Malignancy rates were 1.06 per 100PY in the post-biological setting and increased with older age at biological initiation (1.04 [1.02-1.05], p < 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed. CONCLUSION: This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk.