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LINKED CONTENT: This article is linked to Carbonnel et al paper. To view this article, visit https://doi.org/10.1111/apt.17352 [ABSTRACT FROM AUTHOR]

The article presents a case study related to 24-year-old man with Crohn's disease (CD) was admitted to our hospital with a 9-day history of skin rash, severe asymmetric arthralgia, periarticular swelling, and abdominal pain. Topics include the moderately severe, diffuse abdominal pain, and he had no intestinal bleeding, and the physical examination revealed palpable purpura on the legs and arms, swelling of the left hand, and pain on palpation of several joints without signs of arthritis.

One of the most remarkable aspects of the immune system is its ability to fashion an immune response most appropriate to the activating stimulus. Although the immune system possesses a number of adaptations to accomplish this, an important theme is local immune regulation by site-specific expression of receptors and ligands. One family of molecules that is gaining attention as modulators of the immune system is the carcinoembryonic antigen cell-adhesion molecule family (CEACAM). Functionally, the carcinoembryonic antigen family can mediate cell-cell contact, host-pathogen interactions, and immune regulation. For example, biliary glycoprotein (CEACAM1) can have direct activity on T cells, leading to the inhibition of helper or cytotoxic T cell function. The expression of carcinoembryonic antigen (CEACAM5) on intestinal epithelial cells is involved in the activation of populations of regulatory CD8+ T cells, while a distinct subset of regulatory CD8+ T cells is activated by nonspecific cross-reacting antigen (CEACAM6) on placental trophoblasts. Interestingly, the function and phenotype of these cells depend upon the specific member of the carcinoembryonic antigen family expressed, as well as the antigen-presenting molecule with which it associates. Thus, these glycoproteins comprise a family of molecules whose functions can depend on their nature and context. [ABSTRACT FROM AUTHOR]

Summary: Background: Risk stratification for endoscopic post‐operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. Aims: To assess the current evidence on patient‐related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re‐)resection. Methods: Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient‐related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle‐Ottawa Scale for observational cohort studies and case‐control studies. Results: In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case–control studies, one cross‐sectional study and one individual participant data meta‐analysis) including 6006 patients (median sample size 87 patients [interquartile range 46–170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post‐surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient‐related, microbial, surgical and histopathological factors. Conclusion: Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence‐based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Auzolle et al and Allez and Auzolle papers. To view these articles visit https://doi.org/10.1111/apt.14944 and https://doi.org/10.1111/apt.14978. [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]

Background: Immune checkpoint inhibitors (ICI) improve the prognosis of many cancers but cause immune‐related adverse events (IrAEs). Limited data are available on upper gastrointestinal (UGI) IrAEs. We describe the clinical characteristics, prognosis, and efficacy of medical therapy in patients with UGI IrAEs. Methods: This is a retrospective, multicenter cohort study of patients with UGI symptoms and moderate to severe endoscopic UGI lesions, occurring after ICI. Efficacy of induction medical therapy and at the most recent follow‐up was assessed. Results: Forty patients were included; of these, 34 (85%) received anti‐PD(L)1, either alone (n = 24) or combined with anti CTLA‐4 (n = 10). Eighteen patients (45%) had concomitant enterocolitis. All patients had severe endoscopic lesions (erosions, ulcerations, hemorrhage, or necrotic lesions). Three patients who received an inefficient initial medical treatment had a complicated course: One patient died of enterocolitis, one had a pneumomediastinum, and one developed an ulcerated stricture of the pylorus. Thirty‐five patients (88%) were treated with corticosteroids; 28 patients (80%) responded, and 20 (57%) reached clinical remission. Eight patients were treated with infliximab, and six responded (75%). After a median follow‐up of 11 months, 36 patients (90%) were in corticosteroid‐free clinical remission for their UGI symptoms. Endoscopic lesions persisted in 68% of patients. Conclusions: ICI cause severe UGI IrAEs, which are associated with enterocolitis in approximately half of the patients. Most patients with UGI IrAEs respond to corticosteroids or infliximab. These data support the recommendation to treat these patients without delay and in the same way as those with enterocolitis. [ABSTRACT FROM AUTHOR]

Aim: The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short‐term efficacy in a randomized controlled trial. No long‐term data are available to assess the benefit of this treatment. Methods: This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end‐point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. Results: In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti‐tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow‐up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end‐point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. Conclusion: An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

Summary: Background: The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. Aims: To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. Methods: We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2 months before conception and compared outcomes to women exposed to anti‐TNF treatment during pregnancy. Results: Seventy‐three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti‐TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti‐TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P < 0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. Conclusion: We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs. [ABSTRACT FROM AUTHOR]

Summary: Background: There is no head‐to‐head trial comparing ustekinumab and vedolizumab in patients with Crohn's disease (CD) refractory to anti‐tumour necrosis factor (anti‐TNF). Aim: To compare the effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti‐TNF in a multicentre retrospective observational cohort. Methods: All consecutive patients with CD refractory or intolerant to anti‐TNF who initiated either vedolizumab or ustekinumab were included between May 2014 and August 2018. Clinical remission, steroid‐free clinical remission (SFCR) and treatment persistence were assessed at week 48 with intention‐to‐treat analysis and propensity scores weighted comparison. Results: A total of 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. At week 48, ustekinumab was associated with a higher clinical remission rate (54.4% vs 38.3%; odds ratios, OR = 1.92, 95% CI [1.09‐3.39]) and treatment persistence (71.5% vs 49.7%; OR = 2.54, 95% CI [1.40‐4.62]) than vedolizumab. The rate of SFCR did not differ significantly between ustekinumab and vedolizumab (44.7% vs 34.0%; OR = 1.57, 95% CI [0.88‐2.79]). Subgroup analyses showed that ustekinumab was associated with a higher clinical remission rates at week 48 in patients with ileal location (OR = 3.49, 95% CI [1.33‐9.17) and penetrating behaviour (OR = 6.58, 95% CI [1.91‐22.68]). Regardless of the treatment group, combination therapy at initiation was associated with a higher clinical remission rate at week 48 (OR = 1.93, 95% CI [1.09‐3.43]). Conclusion: This study suggests that ustekinumab is associated with a higher rate of clinical remission and treatment persistence than vedolizumab after 48 weeks of follow‐up, in patients with CD refractory or intolerant to anti‐TNF. The rate of SFCR was not significantly different. [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]

Background Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer ( CRC) in inflammatory bowel ( IBD) disease is controversial. Aim To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Methods Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5- ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. Results By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates ( OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines ( OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). Conclusion In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines. [ABSTRACT FROM AUTHOR]

Background The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. Aim To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. Methods Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). Results Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). Conclusion Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men. [ABSTRACT FROM AUTHOR]