Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Real-World Evidence of Clinical Outcomes of the Use of the Adalimumab Biosimilar SB5 in Rheumatic and Gastrointestinal Immune-Mediated Inflammatory Diseases: 12-Month Data from the PERFUSE Study.

BACKGROUND: There is a need for published data on real-world use of SB5, an adalimumab (ADL) biosimilar approved in Europe in 2017, on the basis of evidence from pre-clinical and analytic data as well as phase I and III clinical studies demonstrating equivalent efficacy and comparable pharmacokinetics, safety and immunogenicity profiles as the reference ADL. OBJECTIVES: The purpose of this study was to estimate patient persistence on SB5 at 12 months post-initiation using clinical and healthcare claims data from the French Système National des Données de Santé (national healthcare claims database, SNDS) in addressing data gaps. METHODS: PERFUSE is a 12-month, observational, multi-centre cohort study of patients with rheumatic or gastrointestinal immune-mediated inflammatory diseases (IMIDs) who initiated routine SB5 treatment between October 2018 and October 2020, either as their first ADL (naïve) or transitioning from another ADL (switched). Clinical data, including disease activity scores, C-reactive protein levels, and dosing information, were collected as available from patient records captured during routine visits to specialist physicians. Persistence data were supplemented with data from the French national healthcare claims database (SNDS). Analyses of clinical data were descriptive, while persistence was assessed using a Kaplan-Meier survival analysis. RESULTS: Overall, 911 patients were included: 507 from rheumatology centres [116 with rheumatoid arthritis (RA), 78 psoriatic arthritis (PsA), and 313 ankylosing spondylitis (AS)] and 404 from gastroenterology centres [316 with Crohn's disease (CD) and 88 ulcerative colitis (UC)]. Among naïve patients, 12-month remission/low activity rates were 58% for RA, 66% for PsA, 59% for AS, 94% for CD, and 85% for UC, increasing significantly from baseline for all indications (p < 0.05). Switched patients' remission rates remained stable between baseline and month 12 (M12) for all indications (p > 0.05). Persistence (95% CI) at M12 among naïve patients was 59% (46.5, 68.8) for RA, 65% (49.7, 77.1) for PsA, 56% (48.3, 62.6) for AS, 70% (63.0, 75.7) for CD, and 42% (30.7, 53.1) for UC, compared to 60% (42.7, 73.7) for RA, 57% (37.3, 72.1) for PsA, 55% (45.8, 64.0) for AS, 63% (53.4, 71.7) for CD, and 56% (27.2, 77.6) for UC among switched patients. No significant differences were observed between naïve and switched patients (p > 0.05). SNDS pairing provided information on 68 of the 132 patients (52%) who were lost to follow-up in the clinical database, of whom 57 (84%) were confirmed persistent at M12 and 11 (16%) non-persistent. Primary treatment failure (naïve patients) and patient decision (switched patients) were the most common reasons stated for treatment discontinuation. CONCLUSIONS: SB5 provides clinically effective treatment of both gastrointestinal and rheumatic IMIDs for naïve and switched patients, with no loss of control observed when switching. Persistence was comparable between naïve and switched populations, though the reasons for non-persistence differed. TRIAL REGISTRY: Trial registration number: Clinical Trials identifier NCT03662919. Trial registration date: 10 September 2018.

Long-Term Neoplastic Risk Associated With Colorectal Strictures in Crohn's Disease: A Multicenter Study.

Background and Aims: While the occurrence of colonic stricture in Crohn's disease (CD) always raises concerns about the risk of cancer, the neoplastic risk associated with its stricture remains poorly known. Methods: All consecutive patients with colorectal stricture complicating CD in 3 academic centers between 1993 and 2022 were included in a retrospective cohort. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. Factors associated with neoplastic stricture were investigated by logistic regression. Results: A total of 88 patients (median age, 25 [interquartile range {IQR}, 19-37] years and median disease duration 12 [4-19] years) with 96 colorectal strictures were included. Strictures were nonpassable by the scope in 61.4% (n = 54) of cases, 70.5% (n = 62) were ulcerated, and 62.5% (n = 55) were symptomatic. Colonic resection and endoscopic balloon dilatation were needed in 47.7% (n = 42) and 28.6% (n = 12) of patients, respectively. After a median follow-up of 21.5 months (IQR [5.5-46.5]), 7 (8%) patients were diagnosed with neoplasia at the colonic stricture site (colonic adenocarcinoma, n = 5; neuroendocrine carcinoma, n = 1; and B-cell lymphoproliferative neoplasia, n = 1), with a median stricture duration at colorectal neoplasia diagnosis of 0 month (IQR [0.0-5.5]). While neoplastic strictures were diagnosed in older patients (58 vs 39 years), with longer disease duration (18 vs 11 years) and frequent obstructive symptoms (57.1% vs 11.1%), no patient-related or stricture-related factor was associated with neoplastic stricture in multivariate analysis. Conclusion: Eight percent of patients with colonic stricture complicating CD developed colorectal cancer. Colorectal cancer and stricture were often diagnosed at the same time and we did not report malignant stricture after 1 year of follow-up.

[Recto-colic graft-versus-host disease (GVH). Diagnostic and prognostic criteria in a cohort of patients from Amiens university hospital]. / Maladie du greffon contre l'hôte (GVH) recto-colique. Critères diagnostiques et pronostiques sur une cohorte de patients du CHU d'Amiens.

INTRODUCTION: Recto-colic graft-versus-host disease (GVHD) is a frequent and serious complication of hematopoietic stem cell allogeneic transplantation, which is sometimes difficult to diagnose. The aim of our study was to identify histological diagnostic and prognostic criteria for recto-colic GVH. MATERIAL AND METHOD: Patients allografted at Amiens university hospital from 2012 to 2017 were retrieved. Those who had a recto-colic biopsy were included and divided into two groups (final diagnosis of GVH and non-GVH), then biopsies were reviewed by 2 pathologists. RESULTS: One hundred and nineteen patients were included. Sixty-seven were allocated to the GVH group and 52 to the non-GVH group. In the GVH group, we observed a significantly greater number of apoptotic bodies (AB) on standard HES staining and with the anti-Caspase 3 immunohistochemistry, cryptolytic AB abscesses, atrophy, regenerative glands and glands lined with eosinophilic cells (P<0.001). Anti-Caspase 3 immunohistochemistry revealed more AB than standard HES staining (P<0.005). But to differentiate GVH cases from non-GVH cases, we obtained a threshold value of 3.5 AB per 10 contiguous crypts on standard HE staining and with the anti-Caspase 3 immunohistochemistry. From 4 AB per 10 contiguous crypts, on HES staining and anti-Caspase 3 immunostaining, the diagnosis of GVH became consistent. No non-GVH case had more than 6 AB per 10 contiguous crypts. GVH patients with more than 8 AB per 10 contiguous crypts had a worse prognosis (P<0.001). CONCLUSION: We confirm the value of AB and their counting in the diagnosis of GVH, with a diagnostic threshold of 4 AB and a prognostic threshold of 8 AB. Glands lined with eosinophilic cells could be an additional diagnostic criterion in favor of GVH to be confirmed by further studies.

Disease burden of patients with moderate to severe ulcerative colitis: A French multicenter real-life study (THEFAR).

BACKGROUND: Specific studies on the impact of ulcerative colitis (UC) and bowel urgency (BU) on disability and quality of life (QoL) of patients on advanced therapies are missing. METHODS: Clinical and therapeutic management data were collected by Gastroenterologists from adult patients with UC treated with advanced therapies. Patients reported outcomes on QoL were collected using patient-reported questionnaires. RESULTS: Forty-one sites enrolled 293 patients. Median age was 42.0 years, median disease duration was 6.0 years. 38.9 % had active disease (partial Mayo score>1). Median treatment duration was 16.9 months. 166 (57.0 %) patients had BU [median UNRS=2] and 78.3 % had fecal incontinence [median Wexner score=8.0]. Moderate to severe disability (IBD-Disk score≥40) was reported in 37.8 % patients. BU patients had a higher Wexner score [10.0 vs 5.2, p < 0.0001] and moderate to severe disability rate (53.7% vs 16.9 %, p < 0.0001), lower QoL and work productivity than those in BU remission: mean EQ-5D-5 L utility [0.846 vs 0.943, p < 0.0001], VAS for self-rated health [66.2 vs 82.1, p < 0.0001], and overall work impairment [35.7% vs 11.3 %, p < 0.0001]. CONCLUSION: The burden of moderate to severe UC, especially in patients with BU, is high. These findings highlight that BU control remains an unmet medical need in UC patients and underscore the need for new innovative treatments.

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. METHODS: All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. RESULTS: A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). CONCLUSION: The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

The GETAID: 40 years of a family story in IBD.

The Groupe d'Etude sur les Affections Inflammatoires Digestives (GETAID) was founded in Paris in 1983 by Professor R Modigliani and colleagues. From the beginning, the aim of this international (France, Belgium and Switzerland), multicentre, French-speaking group was to address clinical questions raised by patients or physicians in their daily practice or the inflammatory bowel diseases community, by focusing on clinical research on treatments through randomised controlled trials, prospective cohorts and cross-sectional studies, quantifying the severity of various facets of the disease when necessary for these studies. This approach very innovative has contributed to the advancement of knowledge in inflammatory bowel diseases by publishing more than 120 original articles in peer-reviewed journals throughout the GETAID 40-year history, most of them in top publications in gastroenterology and hepatology journals. In this paper, we will see what GETAID's contribution has been over the last four decades, review reasons for success and forthcoming challenges.

Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms.

Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn's disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.

Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID.

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

Intestinal Ultrasound, Fecal Calprotectin, and Their Combination to Predict Endoscopic Mucosal Healing in Ulcerative Colitis: A Real-Life Cross-Sectional Study.

BACKGROUND: The development of noninvasive markers to assess mucosal healing in ulcerative colitis (UC) is essential in the treat-to-target era. The aim of this study was to evaluate the performance of intestinal ultrasound (IUS), fecal calprotectin (FC), and their combination to assess mucosal healing in UC patients. METHODS: All consecutive patients between January 2021 and September 2022 with UC who underwent a complete colonoscopy and IUS and/or an FC test within 4 weeks were included in a prospective cohort. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were assessed for each segment. Endoscopic mucosal healing was defined by a Mayo score of 0 to 1. RESULTS: A total of 61 patients were included, of whom 79% showed endoscopic healing (26 Mayo 0 and 11 Mayo 1). Among the patients, 16 (27.6%) of 58 had a BWT <3 mm, and 41 (70.7%) of 58 had no CDS. The sensitivity, specificity, positive predictive value, and negative predictive value of a BWT <3 mm to predict endoscopic mucosal healing were 37%, 77%, 72%, and 44%, respectively. The association of FC <150 µg/g, a BWT <3 mm, and a CDS = 0 increased the specificity and positive predictive value (sensitivity 33%, specificity 94%, positive predictive value 89%, negative predictive value 48%). The combination of a normal IUS, no rectal bleeding, and an FC <172 µg/g identified all patients with mucosal healing. CONCLUSION: The combination of IUS and FC is effective in identifying mucosal healing in UC. Noninvasive evaluation of mucosal healing is possible for most UC patients.

Intestinal ultrasound and fecal calprotectin are efficient noninvasive tools to identify patients with ulcerative colitis (UC) who achieved endoscopic mucosal healing. The combination of intestinal ultrasound and fecal calprotectin is effective to identify mucosal healing in UC in most patients with UC.

Obstetric outcomes of patients with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue. STUDY OBJECTIVE: To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD. METHODS: Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared. RESULTS: One hundred patients were included (81 with Crohn's Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03). CONCLUSION: Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome.

Long-term Outcome of Risankizumab in Crohn's Disease: a Real-world GETAID Study.

BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent.

BACKGROUND: Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. AIM: We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. PATIENTS AND METHODS: In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. RESULTS: Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. CONCLUSION: While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Factors associated with decreased ovarian reserve in Crohn's disease: A systematic review and meta-analysis.

INTRODUCTION: It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in CD are poorly known. MATERIAL AND METHODS: We conducted a comprehensive literature search of multiple electronic databases from inception to June 2022 to identify all studies reporting AMH levels or factors associated with diminished OvR in patients with CD. RESULTS: Of the 48 studies identified in our search, eight (including 418 patients with CD) were finally included. The mean difference (95% confidence interval [CI]) in the AMH level between pooled CD patients and controls was -0.56 (-1.14 to 0.03) (p = 0.06). A history of CD-related surgery was not associated with a lower OvR (odds ratio, OR [95% CI] 1.34, [0.66-2.7]; p = 0.4). While disease activity and perianal disease seems associated with a low OvR, disease location (L2 vs. L1, OR [95% CI] = 95% CI [0.47-7.4]; p = 0.4) and L3 vs. L1 (OR [95% CI] = 1.44 [0.67-3.12]; p = 0.3), CD medication, and disease behavior were not. CONCLUSIONS: Our systematic review and meta-analysis did not identify a significantly low OvR in patients with CD. Contrary to CD-related surgery risk factor, active disease was associated lower AMH levels.

Non-invasive evaluation of mucosal healing by intestinal ultrasound or fecal calprotectin is efficient in Crohn's disease: A cross-sectional study.

INTRODUCTION: Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD. METHODS: All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3. RESULTS: In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28-46), and the median disease duration was 10 years (IQR, 4-19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %. CONCLUSION: Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing.

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

Farming Activities and Risk of Inflammatory Bowel Disease: A French Nationwide Population-based Cohort Study.

BACKGROUND AND AIMS: Epidemiological data regarding inflammatory bowel disease [IBD] are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager [FM] workforce, certain agricultural activities are more strongly associated with IBD than others. METHODS: Nationwide, population-based, insurance claims and electronic health records from all FMs who worked at least once over the period 2002-2016 were used [n = 1 088 561, 69% males]. The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease [CD], and ulcerative colitis [UC], measured as hazard ratios [HRs], after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying time scale. A model was generated for every activity and disease, using a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016. RESULTS: There were 1752 IBD cases, with 704 CD [40.2%] and 1048 UC [59.8%] cases, respectively. Elevated HRs were observed for fruit arboriculture [HR from 1.17 to 1.52] and dairy farming [HR from 1.22 to 1.46] for all IBD, in crop farming for CD only (HR = 1.26, 95% confidence interval [CI]: 1.06-1.49), and in shellfish farming [HR from 2.12 to 2.51] for both CD and IBD. CONCLUSIONS: Further research regarding specific farming activities and exposures likely to modify the microbiota [eg, pesticides, pathogens] is required to identify potential occupational risk factors [agricultural exposome] for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, Cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues.

[Risk factors for high-grade squamous intraepithelial lesions or cervical cancer in chronic inflammatory bowel disease]. / Facteurs de risque de lésions malpighiennes intra-épithéliale de haut grade ou de cancer du col de l'utérus en cas de maladie inflammatoire chronique de l'intestin.

INTRODUCTION: Chronic inflammatory bowel disease (IBD) is thought to increase the risk of high-grade histological intraepithelial lesions (HGIL) and cervical cancer. The risk factors for developing these lesions are poorly understood. MATERIALS AND METHODS: This is a single-center retrospective case-control study including IBD patients followed at our University Hospital Center from 2011 to 2021 who presented with HGIL or cervical cancer. Four controls were case-matched according to IBD type, age, active smoking and multiparity. RESULTS: Eighteen cases and 72 controls were included. We found no significant differences between the 2 groups with regard to mean age at IBD diagnosis, mean duration of IBD, IBD location, history of IBD-related surgery or even association with another chronic inflammatory disease. In our study, the use of immunosuppressants/biotherapies in these patients [50% (9/18) for cases vs. 56% (40/72) for controls; P=0.9] was not a risk factor for IGRA or cervical cancer. Similarly, neither the total duration of exposure to immunosuppressants/biotherapies (9.9±8years for cases vs. 6.6±5.3years for controls; P=0.1), nor combined therapies [11% (2/18) for cases vs. 6% (4/72) for controls; P=0.3], nor azathioprine or methotrexate use [22% (4/18) for cases vs. 11% (8/72) for controls; P=0.3] were found to be risk factors. CONCLUSION: In our study, we found no risk factors for patients with IBD to develop IGRA or cervical cancer.