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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next‐generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. Overall, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localised tumours (72.7% vs 38.2%, P =.003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localised tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR. What's new? Because small bowel adenocarcinomas (SBAs) are quite rare, genomic analyses and prognostic biomarkers are lacking. In this study, the authors found at least one genomic alteration in 90.4% of SBAs. The most frequent alterations occurred at KRAS, TP53, PIK3CA, APC, SMAD4 and ERBB2. Additional alterations were specific to SBAs from patients with Lynch syndrome, while IDH1 mutations were associated with Crohn disease. No association was found between SBA prognosis and specific genomic alterations, except for a trend toward better prognosis with tumors deficient in mismatch repair (dMMR). [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]

Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23–90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz‐Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin‐based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54‐months median follow‐up, the 5‐year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA‐resected tumours, the prognostic factors for OS were grade and T stage. What's new? Small bowel adenocarcinoma is a rare disease but incidences are increasing in Europe and the US because of increases in duodenal cancers. This study from France found that Crohn's disease and Lynch syndrome, a genetic condition associated with colorectal cancers, combined with younger age and poor differentiation predisposed for the disease. The authors also linked poor differentiation and advanced tumor staging with short overall survival in patients with locally resected tumors, underscoring that the prognosis for advanced adenocarcinomas remains poor. [ABSTRACT FROM AUTHOR]

Summary: Background: Cohort studies have described the short‐term effectiveness and safety of vedolizumab in treating patients with Crohn's disease (CD) and ulcerative colitis (UC), but data beyond 1 year are lacking. Aim: To assess the effectiveness and safety of vedolizumab after 162 weeks in patients with UC and CD. Methods: Between June and December 2014, 294 patients including 173 patients with CD and 121 with UC were treated with vedolizumab induction therapy. Among them, 149 continued to be treated with vedolizumab beyond week 54 (78 patients with CD and 71 with UC). Disease activity was assessed using the Harvey‐Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid‐free clinical remission at week 162, computed for the whole population included at week 0. Results: Steroid‐free clinical remission rates at week 162 were 19.9% and 36.1% in patients with CD and UC respectively. Vedolizumab dose optimisation to 300 mg every 4 weeks instead of 300 mg every 8 weeks was at investigator's discretion and occurred in 58.7% and 52.1% of patients with CD and UC respectively. The 1‐, 2‐ and 3‐year persistence rates of vedolizumab were 48.5%, 31.4% and 26.3% respectively, in patients with CD and 61.0%, 49.9% and 42.9% respectively, in patients with UC. No new safety signal was identified. Conclusion: Vedolizumab is able to maintain steroid‐free clinical remission in patients with UC and CD up to week 162. Loss of response resulting in discontinuation of vedolizumab occurred in 10% of patients per year. [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: Genital fistulas represent a devastating complication of Crohn's disease. Only studies with small sample sizes have evaluated the efficacy of anti‐TNF therapy for this complication. Aims: To assess the efficacy of anti‐TNF therapy for genital fistulas complicating Crohn's disease and to identify predictive factors associated with clinical response at 1 year. Methods: Consecutive patients treated with anti‐TNF therapy for genital fistulas complicating Crohn's disease from 1999 to 2016 in 19 French centres from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif were included in a retrospective cohort study. Outcome was clinical fistula closure at 1 year. Results: Among the 204 women with genital fistulas who received anti‐TNF therapy, 131 were analysed. The first anti‐TNF given was infliximab (79%), adalimumab (20%), or certolizumab (1%). At start of anti‐TNF therapy, 56% of patients had seton drainage and 53% had concomitant immunosuppressive treatment. A complementary surgery was performed during the first year in 10 patients (8%). At 1 year, 37% of patients had complete clinical fistula closure, 22% had a partial response, and 41% had no response. Among patients without complementary surgery, 34% (41/121) had complete clinical fistula closure. Only complementary surgery was associated with better response on multivariate analysis (adjusted relative risk: 2.02, 95% CI: 1.25‐3.26, P = 0.0043). Conclusions: In the anti‐TNF era, approximately one‐third of patients with genital fistula in Crohn's disease had complete fistula closure at 1 year. Collaboration between surgeons and gastroenterologists appears to be very important to improve the rate of fistula closure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background After intestinal resection for Crohn's disease, the severity of endoscopic recurrence in the first year following surgery is predictive of clinical outcome. Aim of the study was to assess the impact on clinical recurrence of tailored therapy based on endoscopic findings in the first year following surgery for Crohn's disease. Methods All patients who underwent an intestinal resection for Crohn's disease between 1995 and 2005 at Saint-Louis Hospital were retrospectively included. Time-to-clinical recurrence was compared in two groups: patients who had systematic ileocolonoscopy 6–12 months after intestinal surgery with tailored treatment according to the severity of endoscopic lesions (group C) and patients without systematic endoscopic evaluation (group NC). Results 132 patients (group C = 90, group NC = 42) were included. Probabilities of clinical recurrence were significantly lower in group C (21% and 26% at 3 and 5 years, respectively) compared with group NC (31% and 52% at 3 and 5 years respectively, p = 0.01). Conclusion Tailored treatment according to endoscopic assessment after ileocolonic resection is significantly associated with reduced clinical recurrence rate. [ABSTRACT FROM AUTHOR]

Background: After ileocolic resection in Crohn's disease, studies concerning the influence of the laparoscopic or open approach on clinical and endoscopic recurrences are scarce. Patients and Methods: In a prospective database, we identified all patients operated on between 2004 and 2012 for primary ileocolic resection in Crohn's disease, with at least 6 months of follow-up. The rates of endoscopic recurrence during the first postoperative year and the clinical recurrence at any time during follow-up were measured and compared after the laparoscopic or open approach. Results: Sixty-two patients (mean±standard deviation age, 33.5±12.7 years; 35 females) were operated on through laparoscopy ( n=28) or laparotomy ( n=34). Medical treatment, evolution and phenotype of disease, and postoperative course were comparable in both groups. Mean±standard deviation follow-up was 3.5±1.9 years. Ileocolonoscopy was available in 46 (74.2%) patients. Normal endoscopy or minor recurrence (i0 or i1 grade) was significantly more frequent after laparoscopy (14/24 [58.3%]) versus laparotomy (5/22 [22.7%]) ( P=.019). Clinical recurrence was comparable at 1 year ( P=.116) and at the end of follow-up ( P=.799) after laparoscopy (28.6% and 50%, respectively) or laparotomy (11.8% and 55.9%, respectively). Conclusions: After resection, normal or minor endoscopic lesions (i0 or i1 grade) were more frequent after laparoscopy than after laparotomy. However, clinical recurrence was similar after both techniques. [ABSTRACT FROM AUTHOR]

Background & Aims: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms. Method: A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations. Results: The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30- 0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03). Conclusions: It is not recommended to genotype the studied polymorphisms in routine practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: Total proctocolectomy with definitive ileostomy is the ultimate treatment for refractory colonic Crohn''s disease (CD). Aim of the study was to report the outcome of Crohn''s disease patients after total proctocolectomy with definitive ileostomy. Patients and methods: Between 1990 and 2005, 55 patients underwent total proctocolectomy with definitive ileostomy for Crohn''s disease in our institution. None of them received preventive post-operative treatment. We studied clinical recurrence, need for immunosuppressants (IS), anti-TNF therapy and re-operation in this retrospective cohort. Results: Median follow-up was 5.4 years. Probabilities of clinical Crohn''s disease recurrence were 4%, 27% and 39% at 1, 5 and 8 years, respectively. In multivariate analysis, clinical recurrence rate was significantly higher for patients with penetrating disease behaviour (RR 1.7 IC95% [1.5–19], p =0.05) and absence of perianal disease (RR=1.6, IC95% [1.4–10]; p =0.01). Clinical recurrences were located in terminal ileum in all cases and treated medically in 9 of 16 patients including IS or anti TNF agents in 7 cases. Probabilities of treatment with immunosuppressants or anti-TNF therapy were 4%, 15% and 15% at 1, 5 and 8 years, respectively. Nearly one third of the patients (29%) underwent surgery for mechanical complications (N=11) and/or CD recurrence (N=7). Probabilities of reoperation for Crohn''s disease recurrence were 0%, 10% and 18% at 1, 5 and 8 years, respectively. Conclusion: Recurrence after total proctocolectomy with definitive ileostomy for Crohn''s disease is not uncommon, and in our series often required immunosuppressants or surgical procedure. [Copyright &y& Elsevier]

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]