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Background: Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR., Methods: We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated., Results: From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first ( n  = 2), second ( n  = 4) or third ( n  = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX., Conclusion: IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics. What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation. What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity. How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

Lympho-epithelial interactions between intestinal T resident memory cells (Trm) and the epithelium have been associated with inflammatory bowel disease (IBD) activity. We developed ex vivo autologous organoid-mucosal T cell cocultures to functionally assess lymphoepithelial interactions in Crohn's Disease (CD) patients compared to controls. We demonstrate the direct epithelial cell death induced by autologous mucosal T cells in CD patients but not in controls. These findings were positively correlated with T cell infiltration of the organoids. This potential was inhibited by limiting lympho-epithelial interactions through CD103 and NKG2D blocking antibodies. These data directly demonstrate for the first time the direct deleterious effect of mucosal T cells on the epithelium of CD patients. Such ex-vivo models are promising techniques to unravel the pathophysiology of these diseases and the potential mode of action of current and future therapies., Competing Interests: MA received grant supports from Innate Pharma, Janssen, Takeda, Genentech/Roche, and honoraria for teaching activities or consultancy from Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Novartis, Pfizer, Roche, Takeda, Tillots. NH received honorarium for consultancy from Janssen and Takeda. M-LT-M received honoraria from Abbvie and Janssen. J-MG has been a speaker and/advisory board member for Abbvie, Amgen, Celltrion, Takeda, Janssen and Sanofi Genzyme. SH, JB, HB, KP, LC, MB, VC, BG, CG, DH, JB, HC, LM, CB, AT and LLB have no conflict of interest to declare. MN, JM are employed by Genentech and CB by Institut Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Hammoudi, Hamoudi, Bonnereau, Bottois, Pérez, Bezault, Hassid, Chardiny, Grand, Gergaud, Bonnet, Chedouba, Tran Minh, Gornet, Baudry, Corte, Maggiori, Toubert, McBride, Brochier, Neighbors, Le Bourhis and Allez.)

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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD., Methods: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement., Results: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient., Conclusion: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients., Competing Interests: Conflict of interest L Guillo declares consulting fees for Abbvie. A Amiot declares counseling, boards, lecture, transports or fees from Abbvie, Hospira, Takeda, Gilead, Biocodex, Janssen, Ferring and MSD. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. G Boschetti has served as a speaker and advisory board member for Abbvie, Janssen, Ferring, Norgine, Tillotts, Pfizer, Celltrion, Takeda, Amgen, Sandoz. G Bouguen has received lecture fees from Abbvie, Ferring, MSD, Takeda, Otsuka, Amgen, Biogen, Celtrion, Janssen, Tillots and Pfizer and consultant fees from Takeda, Janssen, Mylan, Vifor Pharma and Gilead. JM Gornet has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda, Roche and Tillots Pharma. J Bonnet has received consulting fees for Amgen. L Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. M Uzzan has served as a speaker for Janssen and Abbvie. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. The remaining authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]., Aim: We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX., Methods: We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication., Results: Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn's disease; 45% combination therapy]. The median IFX duration was 5 years [0.54-14] with a mean infused dose of 533 mg [200-1000] and a mean interval duration of 7.9 weeks [4-10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year., Conclusions: Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease., Aim: To assess the impact of radiotherapy on IBD course., Methods: A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow-up., Results: Sixty-one patients (32 women, mean age 59 years), with 467 patient semesters of follow-up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S + 1 to S + 3 (P = 0.15 vs S-4 to S-1) and 16% (10-25) from S + 4 to S + 6 (P = 0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare., Conclusion: Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period., (© 2020 John Wiley & Sons Ltd.)

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial., Aim: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case-control study., Methods: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non-healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community-acquired infection that required hospitalisation., Results: With a median follow-up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community-acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06-4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38-2.84], P < 0.001) and anti-TNF agents (OR = 2.93, 95% CI [2.02-4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43-0.91], P = 0.01)., Conclusions: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high-risk population when treated with anti-TNF agents., (© 2018 John Wiley & Sons Ltd.)

Background: Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown., Methods: IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer., Results: 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1-30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment., Conclusion: CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial., Methods: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies., Results: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC)., Conclusions: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy., Trial Registration Number: IRB 001508, Paris 7 University., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD., Method: Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry., Results: From the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n=14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p<0.001) and by the presence of IBD severity's hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases., Conclusion: Although low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved., Methods: A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted., Results: A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection., Conclusion: Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: There is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME)., Methods: We followed and collected data from 19,486 patients with IBD (60.3% with Crohn's disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD., Results: Thirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6-1.8; P = .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1-0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis., Conclusions: Patients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Infliximab is effective for the treatment of refractory inflammatory bowel disease (IBD). Nevertheless, up to 40% of patients lose response to infliximab over time. The aim was to assess the clinical value of measuring infliximab trough levels and antibodies to infliximab (ATI) concentrations in IBD patients who lost response to infliximab therapy., Methods: We retrospectively studied records of IBD patients who lost response to infliximab therapy. We first assessed clinical responses of different therapeutic strategies that were applied when patients lost response to infliximab and then we looked at the correlation between clinical response and infliximab trough levels and ATI concentrations., Results: Seventy-six IBD patients were included. 31/76 patients (41%) continued infliximab therapy without any modification, 39 patients (51%) had an intensification of infliximab therapy, five patients (7%) had switched to adalimumab therapy, and one patient (1%) underwent surgery. Clinical response was observed in 27 patients (69%) with an intensification of infliximab therapy. There was no significant difference in mean infliximab trough level at inclusion in patients who responded to intensification of infliximab therapy (3.3 ± 4.1 μg/mL) as compared with patients who did not respond (2.3 ± 2.2 μg/mL, P = 0.85). In all, 16/76 patients (22.4%) presented detectable ATI in the serum. Ten ATI-positive patients had an intensification of infliximab therapy and six (60%) demonstrated a clinical response. After intensification of infliximab therapy the ATI concentration decreased in five patients., Conclusions: In patients with IBD who lose response to infliximab, clinical improvement may occur upon intensification of infliximab therapy, irrespective of infliximab serum concentration or presence of ATI., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background The advent of anti–tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods This French retrospective study (2010–2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results Thirty-six patients were included (median age, 35 years; IQR, 27–48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18–80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60–42.82; P =.015). Anti-TB treatment was longer in this population (median [IQR], 9 [9–12] vs 6 [6–9] months; P =.049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3–10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21–90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy. [ABSTRACT FROM AUTHOR]

Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real‐life long‐term data are currently available. Aims: To assess the real‐world effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. Results: We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti‐TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid‐free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3‐10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. Conclusion: After 52 weeks, over one‐half of patients with refractory UC were still treated by ustekinumab and one‐third were in steroid‐free clinical remission. [ABSTRACT FROM AUTHOR]

Summary: Background: The long‐term outcome of patients with acute severe ulcerative colitis (ASUC) responding to intravenous steroids (IVS) has been poorly reported. Aims: To assess relapse‐free survival in patients with ASUC responding to IVS. Methods: Between January 2006 and December 2017, 142 consecutive patients with ASUC (according to modified Truelove‐and‐Witts criteria) responding to IVS were included in this multicentre retrospective study. Relapse was defined by a partial Mayo Clinic score >4 and/or the need for another maintenance therapy. Results: Among the 142 included patients (100 naïve of immunomodulator and/or biological agent) hospitalised for ASUC, 59 (41.5%) were treated at discharge with 5‐aminosalicylic acid, 60 (42%) with immunomodulators, 18 (13%) with anti‐tumour necrosis factor (TNF) agents and 5 (3.5%) with vedolizumab. After a median follow‐up of 4.8 (2.6‐7.3) years, 90 (63.4%) had relapsed and 12 (8.5%) had required colectomy. The probabilities of relapse‐free survival were 58%, 48% and 40% at 1, 2 and 5 years respectively. The multivariate analysis demonstrated that patients with <6 liquid stools per day at day 3 (hazard ratio 0.56, 95%CI [0.34‐0.91]), a partial Mayo Clinic score <2 at day 5 (0.41 [0.21‐0.80]) and anti‐TNF maintenance therapy (0.37 [0.16‐0.87]) were less likely to relapse. The probabilities of colectomy‐free survival were 96%, 95% and 91% at 1, 2 and 5 years respectively. Conclusion: Despite a high relapse rate, patients with ASUC responding to IVS had a low rate of colectomy after 5 years of follow‐up. Early response to IVS and maintenance therapy with biological agents were associated with a lower rate of relapse. [ABSTRACT FROM AUTHOR]

Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate‐to‐severe ulcerative colitis (UC), but few real‐world data are currently available. Aim: To assess short‐term effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid‐free clinical remission (partial Mayo Clinic score ≤2) at weeks 12‐16 without a rectal bleeding subscore >1. Results: Among the 103 patients included, 70% had been previously exposed to ≥2 anti‐TNF agents and 85% to vedolizumab. At weeks 12‐16, steroid‐free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12‐16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti‐TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid‐free clinical remission at weeks 12‐16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. Conclusion: In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid‐free clinical remission in one‐third of cases at weeks 12‐16. Clinical severity and previous use of anti‐TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12‐16. [ABSTRACT FROM AUTHOR]

Summary: Background: After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo‐terminal ileum. Aim: To identify predictors of early post‐operative endoscopic recurrence. Methods: From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6‐12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. Results: Two hundred and eighty‐nine CD patients were included. Endoscopy within 1 year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty‐two (63%) patients received at least one anti‐TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti‐TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR = 2.48 [IC 95% 1.40‐4.46]), active smoking at surgery (OR = 2.65 [IC 95% 1.44‐4.97]) and previous resection (OR = 3.03 [IC 95% 1.36‐7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post‐operative anti‐TNF treatment decreased the risk of endoscopic recurrence (OR = 0.50 [IC 95% 0.25‐0.96]). Conclusions: Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post‐operative recurrence, while post‐operative anti‐TNF treatment is associated with a lower risk. Linked Content This article is linked to Yamamoto and Kotze, and Imperatore et al papers. To view these articles visit https://doi.org/10.1111/apt.14985 and https://doi.org/10.1111/apt.14989. [ABSTRACT FROM AUTHOR]

Summary: Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial. Aim: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case‐control study. Methods: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non‐healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community‐acquired infection that required hospitalisation. Results: With a median follow‐up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community‐acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06‐4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38‐2.84], P < 0.001) and anti‐TNF agents (OR = 2.93, 95% CI [2.02‐4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43‐0.91], P = 0.01). Conclusions: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high‐risk population when treated with anti‐TNF agents. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 23-year-old man, non-smoking with no significant personal or familial past medical history presented an acute eruption on the face. Topics include magnetic resonance enterography after Infliximab (IFX) revealing a regression of small bowel thickening and disappearance of parietal enhancement on delayed phase; and dermatological examination revealing an itchy and very well limited erythematous papulosquamous eruption of the face and neck.

Background & Aims: The natural killer group 2 member D (NKG2D) is a stimulatory receptor expressed on a subset of mucosal and peripheral CD4+ T cells in patients with Crohn''s disease (CD) and other inflammatory diseases. Ligand activation of NKG2D in patients induces CD4+ T cells to release T-helper (Th) 1 cytokines and become cytotoxic. We investigated the Th17 cytokines produced by T cells that express NKG2D in blood and intestinal mucosa samples from patients with CD. Methods: We isolated CD4+ T cells from peripheral blood and lamina propria samples of patients with CD or ulcerative colitis (UC) and healthy individuals (controls). We analyzed the phenotype and functions of the CD4+NKG2D+ T cells and the cytokines they produce in response to NKG2D stimulation. Results: In patients with CD, CD4+ T cells that express NKG2D produced high levels of interleukin (IL)-17 and IL-22 and expressed high levels of CCR6, the IL-23 receptor, CD161, and RORC (a transcription factor that regulates expression of Th17 cytokines). CD4+ T cells that produced IL-17 expressed high levels of NKG2D and CD161. Costimulation of NKG2D and the T-cell receptor (TCR) significantly increased production of IL-17 and tumor necrosis factor α by CD4+ T cells, compared with activation of only the TCR. CD4+NKG2D+ T cells also responded to Th17 polarization. Conclusions: NKG2D is a functional marker of CD4+ T cells that produce IL-17 in patients with CD, via costimulation of the TCR and NKG2D. Reagents developed to block NKG2D might reduce gastrointestinal inflammation in patients with CD. [Copyright &y& Elsevier]