Confocal laser endomicroscopy as predictive biomarker of clinical and endoscopic efficacy of vedolizumab in ulcerative colitis: The DETECT study.

AIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4ß7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4ß7- and TNF-expressing cells. Positive α4ß7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4ß7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.

Influence of training and expertise on deep neural network attention and human attention during a medical image classification task.

In many different domains, experts can make complex decisions after glancing very briefly at an image. However, the perceptual mechanisms underlying expert performance are still largely unknown. Recently, several machine learning algorithms have been shown to outperform human experts in specific tasks. But these algorithms often behave as black boxes and their information processing pipeline remains unknown. This lack of transparency and interpretability is highly problematic in applications involving human lives, such as health care. One way to "open the black box" is to compute an artificial attention map from the model, which highlights the pixels of the input image that contributed the most to the model decision. In this work, we directly compare human visual attention to machine visual attention when performing the same visual task. We have designed a medical diagnosis task involving the detection of lesions in small bowel endoscopic images. We collected eye movements from novices and gastroenterologist experts while they classified medical images according to their relevance for Crohn's disease diagnosis. We trained three state-of-the-art deep learning models on our carefully labeled dataset. Both humans and machine performed the same task. We extracted artificial attention with six different post hoc methods. We show that the model attention maps are significantly closer to human expert attention maps than to novices', especially for pathological images. As the model gets trained and its performance gets closer to the human experts, the similarity between model and human attention increases. Through the understanding of the similarities between the visual decision-making process of human experts and deep neural networks, we hope to inform both the training of new doctors and the architecture of new algorithms.

Role of ICAM-1 in the Adhesion of T Cells to Enteric Glia: Perspectives in the Formation of Plexitis in Crohn's Disease.

BACKGROUND & AIMS: The presence of myenteric plexitis in the proximal resection margins is a predictive factor of early postoperative recurrence in Crohn's disease. To decipher the mechanisms leading to their formation, T-cell interactions with enteric neural cells were studied in vitro and in vivo. METHODS: T cells close to myenteric neural cells were retrospectively quantified in ileocolonic resections from 9 control subjects with cancer and 20 patients with Crohn's disease. The mechanisms involved in T-cell adhesion were then investigated in co-cultures of T lymphocytes with enteric glial cells (glia). Finally, the implication of adhesion molecules in the development of plexitis and colitis was studied in vitro but also in vivo in Winnie mice. RESULTS: The mean number of T cells close to glia, but not neurons, was significantly higher in the myenteric ganglia of relapsing patients with Crohn's disease (2.42 ± 0.5) as compared with controls (0.36 ± 0.08, P = .0007). Co-culture experiments showed that exposure to proinflammatory cytokines enhanced T-cell adhesion to glia and increased intercellular adhesion molecule-1 (ICAM-1) expression in glia. We next demonstrated that T-cell adhesion to glia was inhibited by an anti-ICAM-1 antibody. Finally, using the Winnie mouse model of colitis, we showed that the blockage of ICAM-1/lymphocyte function-associated antigen-1 (LFA-1) with lifitegrast reduced colitis severity and decreased T-cell infiltration in the myenteric plexus. CONCLUSIONS: Our present work argues for a role of glia-T-cell interaction in the development of myenteric plexitis through the adhesion molecules ICAM-1/LFA-1 and suggests that deciphering the functional consequences of glia-T-cell interaction is important to understand the mechanisms implicated in the development and recurrence of Crohn's disease.

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics.

Background: Patients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels. Methods: Patients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients. Results: In total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas. Conclusions: The prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.

Prevalence of and Factors Associated With Extraintestinal Manifestations and Their Remission in Inflammatory Bowel Disease: The EXTRA-Intestinal Manifestation Prospective Study From the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

INTRODUCTION: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort. METHODS: We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire. RESULTS: A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission. DISCUSSION: One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission.

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4+OTOP2+ absorptive and BEST2+WFDC2+ secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC+KLRD1+HOPX+ γδ+ T cells with RORA+CCL20+S100A4+ TH17 cells and the influx of inflammatory myeloid cells. The EC transcriptome (exemplified by S100A8, HIF1A, TREM1, CXCR1) correlated with clinical, endoscopic, and histological severity of UC in an independent validation cohort (n=649). Furthermore, therapeutic relevance of the observed cellular and transcriptomic changes was investigated in 3 additional published UC cohorts (n=23, 48 and 204 respectively) to reveal that non-response to anti-Tumor Necrosis Factor (anti-TNF) therapy was associated with EC related myeloid cell perturbations. Altogether, these data provide high resolution mapping of the EC to facilitate therapeutic decision-making and personalization of therapy in patients with UC.

Sacral neuromodulation for refractory ulcerative colitis: safety and efficacy in a prospective observational series of eight patients.

PURPOSE: Ulcerative colitis (UC) treatment is mainly based on immunosuppressive therapy. As anti-inflammatory effects of sacral neuromodulation (SNM) have been previously reported in animal models, we conducted a pilot study aimed at assessing clinical, biological, and endoscopic response but also safety of SNM use in UC refractory to medical therapy. METHODS: Adult patients with histologically proven UC resistant to immunosuppressive therapy were invited to enroll in the study. Primary outcome was the rate of UC remission (UCDAI score ≤ 2, without any criteria > 1) at 8 weeks (W8). Secondary outcomes were biological and endoscopic response also evaluated at W8 and W16. Subsequently, every patient was followed every 6 months. Adverse events were prospectively collected for safety assessment during the follow-up. RESULTS: Eight patients, with mean age 47 years old, suffering from UC for 2-13 years were included. There were no complications in relation to SNM procedure. The acceptance of the device was excellent in all patients. Clinical and endoscopic remission was obtained at W8 in one patient (12.5%) and three other patients (37.5%) were responders at W16. At review (mean follow-up of 4 years), two patients (25%) were in remission and two (25%) were responders. CONCLUSION: SNM application is safe in patients suffering from refractory UC. Effects on disease activity were mainly observed after 16 weeks. Larger prospective studies are mandatory, but SNM could be a way to reinforce medical therapy and reduce the use of immunosuppressive drugs.

Adalimumab in Biologic-naïve Patients With Crohn's Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID.

BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.

Comparative Acceptability of Therapeutic Maintenance Regimens in Patients With Inflammatory Bowel Disease: Results From the Nationwide ACCEPT2 Study.

BACKGROUND: Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). METHODS: From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. RESULTS: Among 1850 included patients (65.9% with Crohn's disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size <0.5). From patients' acceptability perspective, superiority and noninferiority cutoff values should be 15% and 5%, respectively. CONCLUSIONS: Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.

Considering both the route of medication delivery and the interval between 2 administrations, we observed a strong impact of patients' experience regarding previous treatments. The most accepted maintenance regimens were subcutaneous injections with interval ≥8 weeks and oral intake.

Distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn's disease stopping infliximab: when the remission state hides different types of residual disease activity.

OBJECTIVE: Despite being in sustained and stable remission, patients with Crohn's disease (CD) stopping anti-tumour necrosis factor α (TNFα) show a high rate of relapse (~50% within 2 years). Characterising non-invasively the biological profiles of those patients is needed to better guide the decision of anti-TNFα withdrawal. DESIGN: Ninety-two immune-related proteins were measured by proximity extension assay in serum of patients with CD (n=102) in sustained steroid-free remission and stopping anti-TNFα (infliximab). As previously shown, a stratification based on time to clinical relapse was used to characterise the distinct biological profiles of relapsers (short-term relapsers: <6 months vs mid/long-term relapsers: >6 months). Associations between protein levels and time to clinical relapse were determined by univariable Cox model. RESULTS: The risk (HR) of mid/long-term clinical relapse was specifically associated with a high serum level of proteins mainly expressed in lymphocytes (LAG3, SH2B3, SIT1; HR: 2.2-4.5; p<0.05), a low serum level of anti-inflammatory effectors (IL-10, HSD11B1; HR: 0.2-0.3; p<0.05) and cellular junction proteins (CDSN, CNTNAP2, CXADR, ITGA11; HR: 0.4; p<0.05). The risk of short-term clinical relapse was specifically associated with a high serum level of pro-inflammatory effectors (IL-6, IL12RB1; HR: 3.5-3.6; p<0.05) and a low or high serum level of proteins mainly expressed in antigen presenting cells (CLEC4A, CLEC4C, CLEC7A, LAMP3; HR: 0.4-4.1; p<0.05). CONCLUSION: We identified distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with CD stopping infliximab. These findings constitute an advance for the development of non-invasive biomarkers guiding the decision of anti-TNFα withdrawal.

Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn's disease: a multicentre retrospective study.

BACKGROUND: No study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn's disease (CD). The aim of the study was to compare the efficacy of biologics in this setting. METHODS: Patients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study. RESULTS: Among the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14-24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively, p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml. CONCLUSIONS: VDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.

Key research questions for implementation of artificial intelligence in capsule endoscopy.

Background: Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. Objectives: In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Design: Modified three-round Delphi consensus online survey. Methods: The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Results: Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). Conclusion: In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.

IL-22BP production is heterogeneously distributed in Crohn's disease.

Crohn's disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.

Saccharomyces cerevisiae I-3856 in irritable bowel syndrome with predominant constipation.

BACKGROUND: Probiotics are a promising solution for managing irritable bowel syndrome (IBS). Saccharomyces cerevisiae (S. cerevisiae) I-3856 has already demonstrated beneficial effects in IBS subjects, particularly in IBS with predominant constipation (IBS-C). AIM: To confirm the efficacy of S. cerevisiae I-3856 in the management of gastrointestinal symptoms in IBS-C. METHODS: A randomized, double-blind, placebo-controlled clinical study was performed in a total of 456 subjects. After a run-in period, subjects were randomly assigned to the group receiving S. cerevisiae I-3856 (8 × 109 CFU daily) or the placebo for 8 wk, and they performed daily self-evaluations of gastrointestinal symptoms. The primary objective was to assess the effect of the probiotic on abdominal pain. The secondary objectives were the evaluation of other gastrointestinal symptoms, bowel movement frequency and consistency, and quality of life (QOL). RESULTS: A significantly higher proportion of abdominal pain responders was reported in the Probiotic group (45.1% vs 33.9%, P = 0.017). A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic vs placebo [P = 0.073, 95%CI: -0.59 (-1.23; 0.05)]. No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups. After 8 wk of supplementation, the overall QOL score was significantly higher in the Probiotic group than in the Placebo group [P = 0.047, 95%CI: 3.86 (0.52; 7.20)]. Furthermore, exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders vs nonresponders. CONCLUSION: The results of this clinical study confirmed the abdominal pain alleviation properties of S. cerevisiae I-3856 in IBS-C. Abdominal pain relief was associated with improved QOL. ClinicalTrials.gov identifier: NCT03150212.

Efficacy and Safety of Infliximab Retreatment in Crohn's Disease: A Multicentre, Prospective, Observational Cohort (REGAIN) Study from the GETAID.

INTRODUCTION: The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. METHODS: We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. RESULTS: At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. DISCUSSION: In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.

Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study.

INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Prevalence of anti-TNF contraindications in Crohn's disease: A cross-sectional survey from the GETAID.

BACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn's disease, assessing each patient's potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians' preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn's disease. Physicians' choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age.

Development of a New Index to Assess Small Bowel Inflammation Severity in Crohn's Disease Using Magnetic Resonance Enterography.

Background: The severity of small bowel (SB) inflammation in Crohn's disease (CD) patients is a key component of the therapeutic choice. We aimed to develop a SB-CD Magnetic Resonance Enterography (MRE) index of Inflammation Severity (CDMRIS). Methods: Each gastroenterologist/radiologist pair in 13 centers selected MREs from 6 patients with SB-CD stratified on their perceived MRE inflammation severity. The 78 blinded MREs were allocated through balanced incomplete block design per severity stratum to these 13 pairs for rating the presence/severity of 13 preselected items for each SB 20-cm diseased segment. Global inflammation severity was evaluated using a 100-cm visual analog scale. Reproducibility of recorded items was evaluated. The CDMRIS was determined through linear mixed modeling as a combination of the numbers of segments with lesions highly correlated to global inflammation severity. Results: Four hundred and forty-two readings were available. Global inflammation severity mean ± SD was 21.0 ± 16.2. The independent predictors explaining 54% of the global inflammation severity variance were the numbers of segments with T1 mild-moderate and severe intensity of enhancement, deep ulceration without fistula, comb sign, fistula, and abscess. Unbiased correlation between CDMRIS and global inflammation severity was 0.76. Conclusions: The CDMRIS is now available to evaluate the severity of SB-CD inflammation. External validation and sensitivity-to-change are mandatory next steps.

A Magnetic Resonance Imaging Index to Predict Crohn's Disease Postoperative Recurrence: The MONITOR Index.

BACKGROUND & AIMS: We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). METHODS: Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. RESULTS: Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. CONCLUSIONS: The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.