BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intraabdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naive patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%- 79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naive patients with CD complicated by an intra-abdominal abscess. ClinicalTrials.gov, Number: NCT02856763

Background and aims In Crohn's disease (CD), a composite therapeutic target was recently recommended, including both objective measurement (endoscopic remission) and Patient-Reported Outcomes (resolution of abdominal pain and normalization of bowel function). All dimensions of health-related quality of life (HRQoL) are impacted: not only bowel symptoms but also systemic symptoms, emotional wellbeing and social function. Thus, understanding the predictors of each HRQoL dimension would improve patient management. However, analysis of these factors has only been found in a few publications, with some limitations. Therefore, this study aimed to explore the evolution of the HRQoL of CD patients during six months after initiation of anti-TNF and to identify its predictors. Methods We analyzed data of 56 patients included in a multicenter prospective cohort study (COQC-PIT). HRQoL measures (using IBDQ-32) and data related to patient, disease and treatment characteristics were collected every two months. Generalized estimating equations were used. Results Overall HRQoL was significantly improved 2 months after anti-TNF initiation, and then stagnated. Patient, disease, and treatment characteristics have differentiated impacts on the overall score and on each dimension of quality of life. Subcutaneous anti-TNF had no significant effect on overall HRQoL, improving only emotional function and bowel symptoms. Concomitant use of corticosteroids and/or immunomodulators impaired almost all dimensions. Having children or working altered bowel symptoms. Disease duration and active smoking negatively impact emotional function and systemic symptoms. Conclusions Each HRQoL dimension, not only bowel symptoms, and their influencing factors should therefore be considered in medical decision-making, especially in months following the initiation of a new treatment such as anti-TNF.

INTRODUCTION: The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. METHODS: We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. RESULTS: At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. DISCUSSION: In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.

Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity.1,2 Despite this clear definition, diagnosis is challenging. The presence of antienterocyte antibodies against the AIE-75kDa antigen3 is a strong but inconstant biomarker. In a recent cohort of 40 AIE patients, antienterocyte antibodies were reported in only 14% (4/28) of the cases, likely caused by the high frequency of patients with primary hypogammaglobulinemia.

Background and objective Anti-TNFs have been shown to significantly improve the health-related quality of life (HRQoL) in Crohn's disease (CD) patients. The purpose of this study was to investigate to what extend the patients' preferences for these intravenous (IV) and subcutaneous (SC) treatments differ based on respondents' quality of life. An online discrete choice experiment (DCE) was conducted to understand patient trade-offs in treatment choice. Methods Fifty-seven Crohn's disease anti-TNF naive patients were asked to choose between two different scenarios, considering the following attributes: mode of administration (MODE), total availability for injection (TIME), speed of onset (DELAY), risk of anti-TNF administration despite a contraindication (RISK) and total monthly out-of-pocket expenses (COST). At the same time, patients completed the IBDQ-32 questionnaire. Conditional logit models without and with interaction terms were estimated to evaluate attribute weights. Results Patients preferred to self-administer SC anti-TNF rather than have a primary care nurse do it, whereas the preference for IV route was negative. After adding interaction terms however, the IV route became preferred for patients with impaired HRQoL, this preference having decreased as HRQoL increased. Surprisingly, patients with impaired HRQoL were less willing to spend more time on treatment, and this effect diminished as HRQoL (overall and in each dimension) became higher. Conclusions HRQoL level changed patients' preferences for the anti-TNF treatment. The results suggest the need to optimise the management of IV infusions in the hospital and reinforce the importance of patient-reported outcome measures (PROMS) as a common practice to improve shared medical decision making.

The pathophysiology of jackhammer esophagus is complex and remains unclear. Radiofrequency catheter ablation is indicated for highly symptomatic and drug-refractory atrial fibrillation. This technique can induce esophageal and nerve lesions, due to thermal injury. In this report, we describe a case of hypercontractile esophagus diagnosed by HRM (high-resolution manometry). Esophageal symptoms and HRM normalized immediately after RFCA, and we discuss the pathophysiology of hypercontractile esophagus.

findings emphasize the importance of Nrf2 in maintaining nNOS a mediated GE in female obese T2DM rodents.CNM and CUR are potential dietary compounds that can alleviate diabetic gastroparesis in women.

Background and Aims: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission. Methods: In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months). Results: At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts >= i2). The Rutgeerts score was significantly correlated with the Watson score (rho = 0.73; P < .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P = .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P = .036). Conclusions: CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.

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.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.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.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).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.

BACKGROUND & AIMS:A combination of infliximab and immunomodulators is the most efficacious treatment for Crohn's disease (CD). Patients have the best outcomes when their serum concentrations of these drugs are above a determined therapeutic threshold. We performed a prospective, randomized trial to determine whether therapeutic drug monitoring (TDM) to maintain serum levels of infliximab above 3 μg/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms.METHODS:We performed a double-blind trial in which 122 biologic-naïve adult patients with active CD (71 female, median age 29.8 years) received induction treatment with infliximab in combination with an immunosuppressant, from July 2012 through September 2015 at 27 centers in Europe. At week 14 of treatment, patients were randomly assigned (1:1:1) to 3 infliximab maintenance groups: dose increases (2 maximum) in steps of 2.5 mg/kg based on clinical symptoms and biomarker analysis and/or serum infliximab concentrations (dose intensification strategy [DIS]1 group); dose increase from 5 to 10 mg/kg based on the same criteria (DIS2 group); dose increase to 10 mg/kg based on clinical symptoms alone (controls). Patients' CD activity index scores, levels of C-reactive protein, fecal levels of calprotectin, and serum concentrations of infliximab were determined at baseline and at weeks 2, 4, 6, 12, and 14 of treatment, and then every 4 weeks thereafter until week 54. The primary endpoint was sustained corticosteroid-free clinical remission (CD activity index <150) from weeks 22 through 54 with no ulcers at week 54.RESULTS:The primary endpoint was reached by 15 (33%) of 45 patients in the DIS1 group, 10 (27%) of 37 patients in the DIS2 group, and 16 (40%) of 40 patients in the control group (P = .50).CONCLUSIONS:In a prospective randomized exploratory trial of patients with active CD, we found increasing dose of infliximab based on a combination of symptoms, biomarkers, and serum drug concentrations does not lead to corticosteroid-free clinical remission in a larger proportion of patients than increasing dose based on symptoms alone.EUDRACT NUMBER:2011-003038-14.

Background and Objectives The pharmacokinetics of infliximab are highly variable and influence clinical response in chronic inflammatory diseases. The goal of this study was to build a Bayesian model allowing predictions of upcoming infliximab concentrations and dosing regimen adjustment, using only one concentration measurement and information regarding the last infliximab infusion. Methods This retrospective study was based on data from 218 patients treated with infliximab in Tours University Hospital who were randomly assigned to learning (two-thirds) or validation (one-third) data subsets. One-compartment pharmacokinetic and time since last dose (TLD) models were built and compared using learning and validation subsets. From these models, Bayesian pharmacokinetic and TLD models using one concentration measurement (1C-PK and 1C-TLD) were designed. The predictive performances of the 1C-TLD model were tested on two external validation cohorts. Results Pharmacokinetic and TLD models described the data satisfactorily and provided accurate parameter estimations. Comparable predictions of infliximab concentrations were obtained from pharmacokinetic versus TLD models, as well as from Bayesian 1C-PK versus 1C-TLD models. The 1C-TLD model showed satisfactory prediction of future infliximab concentrations and provided satisfactory predictions of infliximab steady-state concentration for up to three upcoming visits after a blood sample. Conclusions Accurate individual concentration predictions can be obtained using a single infliximab concentration measurement and information regarding only the last infusion. The 1C-TLD model may help to optimize the dosing regimen of infliximab in routine therapeutic drug monitoring.

In recent decades, the advent of biological therapy has changed the treatment of inflammatory bowel disease (IBD) and has opened new therapeutic endpoints such as mucosal healing (MH). MH incorporated with clinical remission presents a new concept: deep remission, which correlates with a decrease in hospitalization and surgery and improvement in the patient’s quality of life. Several techniques can be used to assess mucosal healing such as endoscopy which remains the gold standard. But considerable variations may exist in the interpretation of the definition of mucosal healing which may also be histological or evaluated by radiological or biological methods. Thus, it is important to study mucosal inflammation by endoscopic scores and by new, more sensitive techniques such as videocapsule endoscopy (VCE), magnetic resonance enterography (MRE), chromoendoscopy and confocal laser endomicroscopy (CLE). Biomarkers, such as fecal calprotectin (FC) were also studied in the evaluation of MH and showed positive results. These methods are currently the subject of validation studies.

Background: Ursodeoxycholic acid (UDCA) therapy is commonly used in intrahepatic cholestasis of pregnancy (ICP).Aim: To evaluate the efficacy and tolerance of UDCA in real-world conditions and to search for factors predictive of response to treatment.Methods: This observational study included 98 consecutive patients suffering from pruritus during pregnancy associated with increased ALT levels or total bile acid (TBA) concentrations, without other causes of cholestasis. The entire ABCB4 gene coding sequence was analyzed by DNA sequencing.Results: UDCA was prescribed until delivery in all patients (mean dose 14.0 mg/kg/day; mean duration 30.4 days). Pruritus improved in 75/98 (76.5%) patients, and totally disappeared before delivery in 25/98 (25.5%). After 2-3 weeks of treatment, ALT levels decreased by more than 50% of base line in 67/86 (77.9%) patients and normalized in 34/86 (39.5%), and TBA concentrations decreased in 28/81 (34.6%). Only one patient stopped the treatment before delivery. On multivariate analysis, ALT >175 IU/1 before treatment was associated with improvement of pruritus (OR 2.97, 95% CI 1.12-7.89, P = 0.029) and with decreased ALT (OR 18.61, 95% CI 3.94-87.99, P = 0.0002). ABCB4 gene mutation was not associated with response to treatment.Conclusion: This study supports the use of UDCA as first line therapy in ICP. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

BACKGROUND & AIMS: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin alpha 4 beta 7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy.METHODS: From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase.RESULTS: Among the 294 patients treated with vedolizumab (mean age, 39.5 +/- 14.0 y; mean disease duration, 10.8 +/- 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma).CONCLUSIONS: In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

Infliximab is an anti-tumor necrosis factor monoclonal antibody approved in chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD) and ulcerative colitis (UC). Infliximab pharmacokinetics is variable between patients, but influence of the underlying disease was never assessed. This study aimed at assessing this influence using a cohort of patients monitored in a single center and with the same assay. Infliximab trough concentrations were determined on samples collected between weeks 0 and 22 after treatment initiation in 218 patients treated for RA, PsA, AS, CD or UC. Infliximab pharmacokinetics was analyzed by a one-compartment population model with first-order elimination rate constant. In AS patients, volume of distribution (V) and elimination clearance (CL) were 5.4 L and 0.24 L/day, respectively. In CD and UC patients, V was 49% and 52% higher than in AS, respectively, and CL was 47% and 60% higher than in AS, respectively. In RA patients, CL was 49% higher than in AS patients. Simulations showed that without methotrexate, a 3mg/kg dosing regimen would lead only 16% of RA patients to reach the target concentration (2.5mg/L) at week 22, whereas target concentrations would be reached in approximately half of RA patients cotreated with methotrexate, as well as half of CD (3.5mg/L) and UC (3.7mg/L) patients. The suboptimality of approved dosing regimens supports the development of dosing optimization based on concentration measurements.

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.

Background and aims Stricture of small intestine is an important complication of Crohn's disease (CD).It often needs resection of gut and finally causes short bowel syndrome.Development of balloon-assisted enteroscopy (BAE) enables approaching small intestinal lesions.BAE can also perform endoscopic balloon dilatation (EBD) for CD strictures.However, EBD often needs re-dilatation because CD is a chronic inflammatory disease and cause restricture.It is reported that mucosal healing is important for better prognosis.Here we compared the outcomes of EBD for small intestinal stricture with or without ulcer in patients CD.Patients and methods 184 patients with L1 or L3 Crohn's disease were examined by single-balloon enteroscope (Olympus, Tokyo, Japan).74 patients had de novo stricture in the small intestine.Indication of endoscopic balloon dilatation is stricture that was not passes by enteroscope (9.2mm diameter), length was less than 5cm, without fistula or deep ulcer, and without steep bending at the stricture.Through-the-scope balloon catheter (CRE Wire-guided Balloon Dilators, Boston Scientific, Natick, MA) was used for EBD.The balloon dilator was inserted to stricture and inflated under direct vision for 2 minutes.Results EBD was performed for 91 strictures in 60 patients who had den novo stricture in the small intestine.In other 14 patients, EBD were not performed because of deep ulcer (43%), fistula (14%), length of stricture(7%), inflammatory stricture(14%), and steep bending (21%).EBD performed patients consisted of 47 men and 13 women.Mean age was 38.7+-11.4years old (range 20-65 y.o.).Immunomodulator and anti-TNF antibody was used in 38% and 53 % of patients respectively.The overall follow-up period was a mean of 283 days (range, 0-861).The whole re-dilatation-free rate after the initial EBD was 79.9% at 180 day, and 53.9% at 1 year.We compared the re-dilatation-free rate in patients with and without ulcer at stricture.The re-dilatation-free rate of with-ulcer stricture (n=64) and without-ulcer stricture (n=27) were 35.9% and 75.7% at 1 year respectively (P<0.001, log-rank test).94.4% of ulcerated strictures needed re-dilatation or surgery within 420 days after initial EBD.As for adverse events, one perforation occurred in a patient and needed the emergent surgery.The lesion was ulcerated in the terminal ileum.No patients developed pancreatitis.Conclusions The re-dilatation-free interval of ulcerated stricture was significantly shorter than that of stricture without ulcer.Mucosal healing is an important factor of avoiding restricture and better prognosis of EBD for small intestinal stricture by Crohn's disease.