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).

Impact of HIV Infection on the Course of Inflammatory Bowel Disease and Drug Safety Profile: A Multicenter GETAID Study.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. METHODS: We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. RESULTS: Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. CONCLUSION: Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.

Prevalence of Self-Reported Venous Thromboembolism and Cardiovascular Risk Factors in Patients with Ulcerative Colitis: The GETAID FOCUS Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). METHODS: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. RESULTS: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. CONCLUSION: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.

Risk of Late Postoperative Recurrence of Crohn's Disease in Patients in Endoscopic Remission After Ileocecal Resection, Over 10 Years at Multiple Centers.

BACKGROUND & AIMS: The risk of recurrence of Crohn's disease (CD) from 1 to 10 years after surgery despite initial endoscopic remission (late post-operative recurrence) is not clear. METHODS: We performed a retrospective study, at 3 inflammatory bowel disease (IBD) centers in France and Belgium, of all patients with CD (n = 86) undergoing an ileocecal resection with curative intent from 2006 through 2016 who did not have endoscopic evidence for recurrence (Rutgeerts score less than i2) at their baseline assessment. Postoperative recurrence after baseline endoscopy was defined as a composite endpoint of at least 1 of the following: clinical recurrence, IBD-related hospitalization, occurrence of bowel damage, need for endoscopic balloon dilatation of the anastomosis, and need to repeat the surgery. Risk of mucosal disease progression was studied as a secondary outcome. RESULTS: The median time between surgery and baseline endoscopy was 7 months (IQR, 5.7-9.5 months); 40 patients (46.5%) received medical prophylaxis in this period. The median follow-up time was 3.5 years (IQR, 1.6-5.3 years). Thirty-five patients (40.7%) had a late post-operative recurrence of CD, with a median time to disease recurrence after baseline endoscopy of 14.2 months (IQR, 6.3-26.1 months). Recurrence status did not differ significantly between patients with Rutgeerts scores of i0 (20/55) or i1 (15/31) at baseline (P = .28) and was independent of medical prophylaxis (16/40 with prophylactic therapy vs 19/46 without prophylactic therapy; P = .90). Mucosal disease progressed in 29 of the 71 patients (40.8%) with available data. We did not identify risk factors for late post-operative recurrence of CD or mucosal disease progression. CONCLUSIONS: Among patients with CD treated by ileocecal resection, 40% of patients had a late recurrence, despite initial endoscopic remission, after a median follow-up time of 3.5 years. Tight monitoring of these patients is recommended beyond 18 months.

Diet as an environmental trigger in inflammatory bowel disease: a retrospective comparative study in two European cohorts.

BACKGROUND AND AIMS: inflammatory bowel disease development has been associated with several environmental factors, among which, diet can play a key role, probably due to a westernized lifestyle. However, its involvement in the pathogenesis of inflammatory bowel disease (IBD) is difficult to demonstrate. The aim of this study was to analyze dietary composition in a Romanian and Belgian population with IBD. METHODS: an observational retrospective comparative study was performed using two European cohorts (Romanian and Belgian). The IBD group included 76 Romanian and 53 Belgian patients with an IBD diagnosis, while the control group included a total of 56 healthy people (35 Romanians and 21 Belgians). All subjects were interviewed and asked to fill in a questionnaire regarding diet. RESULTS: in the entire IBD cohort (Romanian + Belgian), a significantly increased consumption of sweets (OR 3.36 [95 % CI 1.6,7]), processed and high fat meat (OR 2.5 [95 % CI 1.4, 4.7], fried food (OR 9.5 [3.8, 23.6]), salt (OR 2.8 [1.5, 5.3]), ice cream (OR 3.25 [1.1, 9.8]), mayonnaise (OR 3.49 [1.1, 10.3]), margarine (OR 5.63 [1.64, 19.33]) and chips/nachos/other snacks (OR 2.3 [0.97, 5.73]) were found compared to the healthy control group. The intake of seeds, nuts (OR 0.26 [0.14, 0.52]) and yoghurt consumption (OR 0.44 [0.23, 0.83]) was lower in the IBD group compared to the control group. CONCLUSION: a westernized diet with increased consumption of sweets, processed food, high fat meat, fried food, salt, margarine, snacks, ice cream and mayonnaise seems to be a risk factor for IBD in Romanian and Belgian IBD patients. Intake of seeds, nuts and yoghurt may be a protective factor.

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn's Disease in Sustained Remission.

BACKGROUND & AIMS: Little is known about long-term outcomes of patients with Crohn's disease (CD) after infliximab withdrawal. We aimed to describe the long-term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn. METHODS: We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow-up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de-escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred. RESULTS: Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow-up time was 7 years. Twenty-one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1-30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5-42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2-26.8) whereas 70.2% of patients had no failure of the de-escalation strategy (95% CI, 60.2-80.1). Factors independently associated with major complications were upper-gastrointestinal location of disease, white blood cell count ≥ 5.0 × 109/L, and hemoglobin level ≤12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal. CONCLUSIONS: In a long-term follow-up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de-escalation strategy (no major complication and no failure of infliximab restart).

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS: We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS: We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS: In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

[Interest of confocal endomicroscopy for the management of chronic inflammatory bowel disease]. / Endomicroscopie confocale dans la prise en charge des maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases are chronic diseases whose long-term evolution depends on the depth of remission. Their clinical and endoscopic evaluation is imperfect. The development of confocal endomicroscopy allows microscopic images to be obtained in vivo. These microscopic data are correlated with the activity of the disease. They predict a possible relapse of the disease and also predict the response to treatment with a biological agent, which allows to modify the therapy before the relapse or to make a rational choice between the different biological agents before introducing a new treatment.

Les maladies inflammatoires intestinales sont des maladies chroniques dont l'évolution au long cours dépend de la profondeur de la rémission. Leur évaluation clinique et endoscopique est imparfaite. Le développement de l'endomicroscopie confocale permet d'obtenir des images microscopiques in vivo qui sont corrélées à l'activité de la maladie. Ces données microscopiques permettent de prédire une éventuelle rechute de la maladie et la réponse au traitement par un agent biologique, ce qui amène à modifier la thérapeutique avant la rechute ou de réaliser un choix rationnel entre les différents agents biologiques avant d'instaurer un nouveau traitement.

Role of endoscopy, cross-sectional imaging and biomarkers in Crohn's disease monitoring.

Crohn's disease is characterised by recurrent and/or chronic inflammation of the gastrointestinal tract leading to cumulative intestinal tissue damage. Treatment tailoring to try to prevent this tissue damage as well as achieve optimal benefit/risk ratio over the whole disease course is becoming an important aspect of Crohn's disease management. For decades, clinical symptoms have been the main trigger for diagnostic procedures and treatment strategy adaptations. However, the correlation between symptoms and intestinal lesions is only weak. Furthermore, preliminary evidence suggests that a state of remission beyond the simple control of clinical symptoms, and including mucosal healing, may be associated with better disease outcome. Therefore monitoring the disease through the use of endoscopy and cross-sectional imaging is proposed. However, the degree of mucosal or bowel wall healing that needs to be reached to improve disease outcome has not been appropriately studied. Furthermore, owing to their invasive nature and cost, endoscopy and cross-sectional imaging are not optimal tools for the patients or the payers. The use of biomarkers as surrogate markers of intestinal and systemic inflammation might help. Two biomarkers have been most broadly assessed in Crohn's disease: C-reactive protein and faecal calprotectin. These markers correlate significantly with endoscopic lesions, with the risk of relapse and with response to therapy. They could be used to help make decisions about diagnostic procedures and treatment. In particular, with the use of appropriate threshold values, they could determine the need for endoscopic or medical imaging procedures to confirm the disease activity state.

In-Depth Assessment of Endoscopic Remission in Inflammatory Bowel Disease Treated by Anti-TNF or Vedolizumab.

BACKGROUND AND AIMS: Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients. METHODS: We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded. RESULTS: Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline. CONCLUSION: Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.

We studied the abnormalities found by confocal endomicroscopy in patients with chronic inflammatory disease in deep endoscopic remission under immunosuppressive treatment. Relapse was not associated with the abnormalities found, which, although numerous, remain of unknown significance.

Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease.

At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.

Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID.

BACKGROUND: Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS: We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year. RESULTS: All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]. CONCLUSION: Tofacitinib may offer a therapeutic option for patients with refractory UP.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.

Clinical and MRI Evolution After Local Injection of Bone Marrow-Derived Mesenchymal Stem Cells in Perianal Fistulae in Crohn's Disease: Results From a Prospective Monocentric Study.

BACKGROUND: Local injection of adipose tissue-derived mesenchymal stem cells [MSCs] is effective in fistulizing perianal Crohn's disease [CD]. Less is known about bone marrow-derived MSCs and little is known about predictive factors of response and magnetic resonance imaging [MRI] evolution of the fistulae after MSC injection. Our aims were to evaluate the safety and clinical outcome of bone marrow-derived MSC injection for perianal fistulizing CD, to evaluate the MRI evolution of the fistulae and to identify factors associated with fistula closure. PATIENTS AND METHODS: All CD patients with perianal fistula and appropriate drainage with a seton without abscess at MRI were eligible. Clinical examination, biomarkers and pelvic MRI were performed at weeks 0, 12 and 48. The clinical outcome was assessed by closure of the treated external openings at clinical examination and MRI exploration. RESULTS: Sixteen patients with a median age of 49 years and a median duration of perianal CD of 8 months were included. No unexpected safety event occurred. At weeks 12 and 48, 9/16 and 8/16 patients had complete fistula[e] closure, respectively, whereas 11/16 patients had at least partial closure. At MRI, the degree of fibrosis increased significantly after MSC injection. In total, 86% of patients with >80% of fibrosis of the fistula tract at week 48 had fistula closure. Fistula closure at week 12 was predictive of fistula closure at week 48. The MAGNIFI-CD did not change significantly over time. CONCLUSION: Open-label injection of bone marrow-derived MSCs was safe and was effective in half of the patients in fistulizing perianal CD and induced significant MRI changes associated with favourable clinical outcome.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease-a Case Series.

BACKGROUND AND AIM: Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP. METHODS: PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form. RESULTS: In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40-68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [n = 12], thiopurines [n = 10], infliximab [n = 4], ciclosporin [n = 2], methotrexate [n = 1], and tacrolimus [n = 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others. CONCLUSION: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy.

Early Post-Operative Endoscopy Is Associated with Lower Surgical Recurrence of Crohn's Disease: A Retrospective Study of Three Successive Cohorts.

Background: The severity of endoscopic recurrence during the first year after intestinal resection for Crohn's disease is predictive of clinical recurrence. The aim of our study was to assess the impact of the implementation of an ileocolonoscopy during the first year after surgery on surgical recurrence. Methods: All patients who underwent a first intestinal resection for Crohn's disease between 1992 and 2018 at the University Hospital of Liège were retrospectively included. The time to surgical recurrence was compared in three successive groups of patients operated on in the period 1992-2001 (group A), 2002-2011 (group B), and 2012-2020 (group C) using the Kaplan-Meier method and the Log-Rank test. To identify independent prognostic factors, a multivariate analysis was used via the Cox model. Results: 223 patients (group A = 69, group B = 94, group C = 60) were included. Probabilities of surgical recurrence were significantly lower in group C (2.2% and 4.7% at 3 and 5 years, respectively) compared with group B (4.2% and 7.6% at 3 and 5 years, respectively) and with group A (9% and 18.2% at 3 and 5 years, respectively) (p = 0.0089). Ileocolonoscopy during the year after surgery was associated with a significantly reduced surgical recurrence rate in univariate and multivariate analysis (HR = 0.31, p = 0.0049). Conclusion: The implementation of an early ileocolonoscopy after surgery for Crohn's disease since early 2000 has been associated with a reduced surgical recurrence over the last 30 years.

Mesenchymal Stem Cell Injection in Crohn's Disease Strictures: A Phase I-II Clinical Study.

BACKGROUND AND AIM: Mesenchymal stem cells [MSCs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn's disease [CD] strictures. In this phase I-II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures. METHODS: CD patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the four quadrants of the stricture. Adverse events and clinical scores were evaluated at each follow-up visit and endoscopy and magnetic resonance enterography were performed at baseline, Week [W]12 and W48. The main judgement criterion for efficacy was the complete [defined by the ability to pass the ileocolonoscope] or partial [defined by a diameter increase] resolution of the stricture at W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48. RESULTS: We performed 11 MSC injections in 10 CD patients [three primary and seven anastomotic strictures; one stricture injected twice]. MSC injections were well tolerated but four hospitalisations for occlusion were reported. At W12, five patients presented a complete or partial resolution of the stricture [two complete and three partial]. Seven patients were re-evaluated at W48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution. The evolution of clinical scores between W0, W12, and W48 was not statistically significant. CONCLUSIONS: MSCs injection in CD stricture was well tolerated and may offer a benefit.

Bariatric Surgery in Patients With Inflammatory Bowel Disease: A Case-Control Study from the GETAID.

BACKGROUND: The prevalence of obesity and the number of bariatric surgeries in both the general population and in patients with inflammatory bowel disease (IBD) have increased significantly in recent years. Due to small sample sizes and the lack of adequate controls, no definite conclusions can be drawn from the available studies on the safety and efficacy of bariatric surgery (BS) in patients with IBD. Our aim was to assess safety, weight loss, and deficiencies in patients with IBD and obesity who underwent BS and compare findings to a control group. METHODS: Patients with IBD and a history of BS were retrospectively recruited to centers belonging to the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Patients were matched 1:2 for age, sex, body mass index (BMI), hospital of surgery, and type of BS with non-IBD patients who underwent BS. Complications, rehospitalizations, weight, and deficiencies after BS were collected in cases and controls. RESULTS: We included 88 procedures in 85 patients (64 Crohn's disease, 20 ulcerative colitis, 1 unclassified IBD) with a mean BMI of 41.6 ± 5.9 kg/m2. Bariatric surgery included Roux-en-Y gastric bypass (n = 3), sleeve gastrectomy (n = 73), and gastric banding (n = 12). Eight (9%) complications were reported, including 4 (5%) requiring surgery. At a mean follow-up of 34 months, mean weight was 88.6 ± 22.4 kg. No difference was observed between cases and controls for postoperative complications (P = .31), proportion of weight loss (P = .27), or postoperative deficiencies (P = .99). CONCLUSIONS: Bariatric surgery is a safe and effective procedure in patients with IBD and obesity; outcomes in this patient group were similar to those observed in a control population.

Proteomics Highlights Common and Distinct Pathophysiological Processes Associated with Ileal and Colonic Ulcers in Crohn's Disease.

BACKGROUND AND AIMS: Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. METHODS: The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn's disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry. RESULTS: In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial-mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges. CONCLUSION: This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.