Development and Validation of a Score to Assess Transmural Healing and Response in Patients With Crohn's Disease.

BACKGROUND & AIMS: Because transmural healing (TH) could be the best therapeutic target in Crohn's disease (CD), we aimed to build and validate a score to assess TH and transmural response (TR), and to confirm their association with favorable CD outcomes. METHODS: DEVISE-CD project encompassed 2 retrospective cohorts (274 and 224 patients with CD for development and validation phase, retrospectively) and 1 multicenter prospective validation cohort (N = 46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary end points were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin <250 at 1 year for retrospective and prospective validation cohorts, respectively. RESULTS: Edema, ulcer, contrast enhancement, diffusion-weighted hyperintensity, fat wrapping, bowel thickening (>3 mm), and enlarged lymph nodes were associated to higher risk of bowel damage progression (P < .01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (P < .0001). Bowel thickness had the highest sensitivity to change after treatment (standardized mean difference = 0.30 ± 1.0; P = .001). C-score was calculated as 0.2x(bowel thickness-3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score <0.5; hazard ratio [HR], 0.28 [0.13-0.63]; P = .002; adjusted HR [aHR], 0.15 [0.04-0.53]; P = .003), TR50 (50% decrease of C-score; HR, 0.30 [0.15-0.63]; P = .001; aHR, 0.36 [0.14-0.88]; P = .025), or TR25 (25% decrease of C-score; HR, 0.37 [0.19-0.71]; P = .003; aHR, 0.46 [0.23-0.94]; P = .034) prevented bowel damage progression in development and validation cohorts, respectively. In the prospective validation cohort, achieving TH (OR, 4.6 [1.3-15.6]; P = .016), TR50 (OR, 6.9 [1.8-26.0]; P = .008), or TR25 (OR, 6.0 [1.6-22.3]; P = .008) after 12 weeks of anti-tumor necrosis factor therapy led to higher rate of corticosteroid-free remission at 1 year. CONCLUSIONS: C-score is a validated, reliable, and easy-to-use tool to assess TH and TR in patients with CD.

Outcomes of bariatric surgery in patients with inflammatory bowel disease from a French nationwide database.

BACKGROUND: The outcomes of bariatric surgery (BS) in patients with chronic inflammatory bowel disease (IBD) remain rarely described. We aimed to evaluate the 90-day morbidity and mortality rates, and the risk of IBD complications 2 years after BS. METHOD: Patients from the French Programme de Médicalisation des Systèmes d'Information (PMSI) database who underwent a primary BS between 2016 and 2018 were included. We identified patients with a previous diagnosis of IBD. Postoperative 90-day (POD90) morbidity and mortality rates were compared between the two groups. The evolution of IBD was followed 2 years after BS. RESULTS: Between 2016 and 2018, 138 980 patients underwent primary BS, including 587 patients with IBD: 326 (55.5 per cent) with Crohn's disease (CD) and 261 (44.5 per cent) with ulcerative colitis (UC). The preferred surgical technique was sleeve gastrectomy, especially in the IBD group (81.1 per cent), followed by gastric bypass (14.6 per cent). Patients with IBD had more comorbidities (Charlson Comorbidity Index of 1 or more, hypertension, and diabetes; P < 0.001) than those without IBD. The POD90 mortality rate did not differ between the two groups (0.049 per cent in the IBD group versus 0 per cent in the non-IBD group), but more unscheduled rehospitalizations at POD90 were observed in patients with IBD (6.0 per cent versus 3.7 per cent; P = 0.004). Two years after BS, 86 patients (14.6 per cent) in the IBD group had at least one unplanned readmission for the management of their IBD; 15 patients stayed for 3 or more days. After multivariable analysis, patients with CD had an independent elevated risk of IBD-related unplanned readmissions 2 years after BS versus UC (adjusted odds ratio 1.90, 95 per cent c.i. 1.22 to 2.97; P = 0.005). CONCLUSION: In a highly selected cohort of patients with well-controlled IBD, BS did not result in added mortality or morbidity. A point of vigilance must be underlined regarding BS in patients with CD.

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate.

AIM: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). METHODS: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. RESULTS: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). CONCLUSION: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease.

AIM: The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.

Natural History of Perianal Crohn's Disease: Long-term Follow-up of a Population-Based Cohort.

BACKGROUND AND AIMS: The natural history of perianal Crohn's disease (PCD) remains poorly described and is mainly based on retrospective studies from referral centers. The aim of this study was to assess the incidence, outcomes and predictors of the onset of PCD. METHODS: All incident cases of patients diagnosed with possible CD were prospectively registered from 1994 to 1997 in Brittany, a limited area in France. At diagnosis, the clinical features of perianal disease were recorded. All patient charts were reviewed from the diagnosis to the last clinic visit in 2015. RESULTS: Among the 272 out of 331 incident CD patients followed up, 51 (18.7%) patients had PCD at diagnosis. After a mean follow-up of 12.8 years, 93 (34%) patients developed PCD. The cumulative probabilities of perianal CD occurrence were 22%, 29%, and 32% after 1 year, 5 years, and 10 years, respectively. The cumulative probabilities of anal ulceration were 14%, and 19% after 1 year and 10 years, respectively. Extraintestinal manifestations were associated with the occurrence of anal ulceration. The cumulative probabilities of fistulizing PCD were 11%, 16%, and 19% after 1 year, 5 years, and 10 years, respectively. Extraintestinal manifestations, rectal involvement and anal ulceration were predictors of fistulizing PCD. The cumulative probability of developing anal stricture was 4% after 10 years. CONCLUSIONS: PCD is frequently observed during CD, in approximately one-third of patients. These data underline the need for targeted therapeutic research on primary perianal lesions (proctitis, anal ulceration) to avoid the onset of fistulizing perianal disease.

Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study.

INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Acute hepatitis B virus infection despite vaccination in a patient treated by infliximab: a case report.

BACKGROUND: Despite an effective vaccine, hepatitis B remains a major global health problem due to its significant morbidity and mortality. Vaccination in immunosuppressed patients such as those treated for an inflammatory bowel disease (IBD) can be less effective. This case describes an uncommon original diagnosis of an acute hepatitis B infection occurring in a vaccinated but immunocompromised IBD patient under long-term infliximab treatment. A low anti-HBs titer and the presence of HBsAg escape mutations are possible hypotheses to explain this unexpected infection. CASE PRESENTATION: A 28-year-old Caucasian male, regularly followed-up for a Crohn's disease treated by infliximab, was regularly screened for sexually transmissible infections because of at-risk behaviors. Despite a correct immunization scheme against hepatitis B virus (HBV), an active HBV infection was diagnosed during one of those screenings. Retrospective testing of a sample collected 6 months earlier was in favor of an evolution from an acute hepatitis B toward a chronic hepatitis B. The patient has always had a low anti-HBs antibody levels (near the threshold of 10 IU/L) possibly explaining his infection. In addition, HBV sequencing revealed a genotype A2 HBV strain, carrying the sD144A substitution on the S protein, known as a potential immune escape variant. Dual therapy combining tenofovir disoproxil fumarate and emtricitabine, active against HBV but also efficient as an HIV pre-exposure prophylaxis, was initiated. Ten months after treatment initiation, all surrogate biochemical and virological endpoints for HBV functional cure were achieved. Treatment and periodical monitoring are being maintained. CONCLUSION: Emphasis should be placed on HBV screening, vaccination and regular monitoring of patients under long-term immunosuppressive therapy, particularly those with at-risk behaviors.

Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn's disease: a multicentre retrospective study.

BACKGROUND: No study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn's disease (CD). The aim of the study was to compare the efficacy of biologics in this setting. METHODS: Patients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study. RESULTS: Among the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14-24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively, p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml. CONCLUSIONS: VDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.

Iron Deficiency in Patients with Inflammatory Bowel Diseases: A Prospective Multicenter Cross-Sectional Study.

BACKGROUND: Iron deficiency (ID) is a frequent condition in patients with inflammatory bowel disease (IBD). AIM: Our aim was to investigate the prevalence of ID in patients with IBD. METHODS: This was a prospective multicenter cross-sectional study conducted in 21 gastroenterology departments in France between January and March 2020. All adult patients with confirmed IBD who were admitted to the hospital were eligible for inclusion. ID was defined as ferritinemia ≤ 100 µg/L in patients with signs of inflammation (C-reactive protein (CRP) ≥ 5 mg/L) or ferritinemia < 30 µg/L in the absence of inflammation. RESULTS: In total, 1036 IBD (685 Crohn's disease and 351 ulcerative colitis) patients (52.1% women) with a mean age of 41.8 ± 15.5 years were recruited. Approximately half of the patients (504, 51.1%) were in disease remission at the time of enrollment. Systematic monitoring of iron status was performed in 12/21 (57%) participating centers, including measurements of ferritin (12/12, 100%), hemoglobin (11/12, 92%), transferrin saturation (TSAT) (6/12, 50.0%), and serum iron (5/12, 42%). About one-fifth of the patients had been treated with intravenous iron (218, 21.0%), whereas only a small percentage received oral iron (36, 3.5%). ID occurred in 97 patients (23.7% CI 95% 19.8-28.1). Patients with moderate/severe IBD activity (OR: 3.66; CI 95% 24.4-61.2; p = 0.007) or concomitant anemia (OR: 3.66; CI 95% 1.97-6.78; p < 0.001) had an increased likelihood of having ID. CONCLUSION: Patients with moderate/severe IBD activity or concomitant anemia are at increased risk of ID. Early detection and management of ID in patients with IBD is recommended.

Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlates With Rate of Infection.

BACKGROUND & AIMS: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features. METHODS: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received an infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC). RESULTS: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938 ± 1427 mg.d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P = .046), IBD flare (OR, 2.71; P = .006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P = .02). The ΣAUC was higher in patients with an occurrence of infection (P = .04) and correlated with the number of infections (P = .04). Trough concentration of infliximab alone was not associated with infection. CONCLUSIONS: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.

Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease.

BACKGROUND & AIMS: Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. METHODS: We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. RESULTS: After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. CONCLUSIONS: In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

Efficacy of Tumor Necrosis Factor Antagonist Treatment in Patients With Refractory Ulcerative Proctitis.

BACKGROUND & AIMS: It is a challenge to manage patients with ulcerative proctitis (UP) refractory to standard therapy. We investigated the effectiveness of tumor necrosis factor (TNF) antagonists in a large cohort of patients with refractory UP. METHODS: We conducted a nationwide retrospective cohort study of 104 consecutive patients with active UP refractory to conventional therapies, treated at 1 of 15 centers in France or 1 center in Belgium (the GETAID cohort). Patients received at least 1 injection of anti-TNF (infliximab, adalimumab, golimumab) from October 2006 through February 2017. Clinical response was defined as significant improvement in UC-related symptoms, and remission as complete disappearance of UC-related symptoms, each determined by treating physicians. We collected demographic, clinical, and treatment data. The median duration of follow-up was 24 months (interquartile range, 13-51 months). The primary outcome was clinical response of UP to anti-TNF treatment. RESULTS: Overall, 80 patients (77%) had a clinical response to anti-TNF therapy and 52 patients (50%) achieved clinical remission. Extra-intestinal manifestations (odds ratio OR, 0.24; 95% CI, 0.08-0.7), ongoing treatment with topical steroids (OR, 0.14; 95% CI, 0.03-0.73), and ongoing treatment with topical 5-aminosalycilates (OR, 0.21; 95% CI, 0.07-0.62) were significantly associated with the absence of clinical remission. Sixty percent (38/63) of the patients who had endoscopic assessment during follow up had mucosal healing. Among the overall population (n = 104), the cumulative probabilities of sustained clinical remission were 87.6% ± 3.4% at 1 year and 74.7% ± 4.8% at 2 years. CONCLUSIONS: In a retrospective study of 104 patients with refractory UP, anti-TNF therapy induced clinical remission in 50% and mucosal healing in 60%. About two thirds of the patients were still receiving anti-TNF therapy at 2 years.

Urinary biomarkers profiles in patients with neurogenic detrusor overactivity according to their neurological condition.

OBJECTIVES: The aim of this study was to investigate the disease-specific urinary levels variations of neurotrophins (NGF, BDNF), mediators of inflammation (TGFß-1, PGE-2) and markers of extracellular matrix alterations (TIMP-2) in patients with multiple sclerosis (MS) spinal cord injury (SCI), or spina bifida (SB), and neurogenic detrusor overactivity (NDO). METHODS: A prospective single-center study was conducted between March 2015 and March 2017. Patients aged over 18 years old, with neurological disease, with a urodynamic diagnosis of NDO were included. The urinary levels of NGF, BDNF, TIMP-2, PGE 2, and TGF-ß1 were measured using dedicated ELISA kits. RESULTS: Forty-one patients were included: 6 with MS, 20 with SCI, and 15 with spina bifida. The average urinary level of NGF/Cr was significantly higher in MS patients compared to other neurologic populations (8 vs. 0.56 vs. 1.25 pg/mg of creatinine; p = 0.001) as well for the average urinary level of BDNF (88.3 vs. 5 vs. 4.8 pg/mg of creatinine; p < 0.0001). SCI patients had a significantly lower level of TGFß-1 than SB patients (p = 0.04). The urinary level of PGE2 was significantly correlated with the Body Mass Index (r = 0.61; p = 0.0002). CONCLUSION: All NDO may not be created equal from the molecular standpoint. Multiple sclerosis patients had higher urinary levels of neurotrophins than in other neurologic populations with NDO. Urinary TGFß-1, a strong determinant of extracellular matrix, was significantly higher in spina bifida patients compared to SCI patients. These findings underscore the importance of using and interpreting those possible urinary markers in a disease-specific fashion.

Defecation disorders in Spina Bifida: Realistic goals and best therapeutic approaches.

AIMS: Spina Bifida (SB) is a rare congenital condition that frequently impairs the neurological control of both fecal continence and defecation. Several therapeutic strategies have been proposed but impact assessment is lacking. Our objectives were to quantify the symptomatic improvement and to determine the optimal strategy in this rare condition where randomized controlled trials are difficult to conduct. METHODS: Data were extracted from a prospective database. The present analysis focused on patients having undergone at least two gastroenterological assessments. A standardized therapeutic approach was used from the first visit. Improvement was quantified by the variation of quantified symptomatic scores. RESULTS: The data of of 57 adults with SB (gender F/M: 30/27 [52.6/47.4%]; mean age: 33.8 [18.5] years) were extracted. After a mean follow-up of 46 months, 23/57 patients (40.4%) had at least improvement of one point of the Cleveland Clinic Incontinence score (CCIS); 13/57 (22.8%) reported a significant improvement of continence (delta score >50%). Five of the twelve patients (41.6%) with CCIS < 5 at baseline became incontinent over time. The neurological level was not associated with a worse continence outcome. Work on stool consistency and transanal irrigation were the most useful strategies in those with significant improvement of continence. CONCLUSIONS: Using conventional strategies, a benefit on fecal continence occurs in only one out of five patients suffering from Spina Bifida and continent patients at baseline can develop fecal incontinence over time. A strategy targeting improved control of defecation (transanal irrigation) and a standardization of follow-up protocol might be beneficial.

Urinary TIMP-2 and MMP-2 are significantly associated with poor bladder compliance in adult patients with spina bifida.

AIMS: To assess the predictive values of six urinary markers (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], matrix metalloproteinase 2 [MMP-2], tissue inhibitor metalloproteinase 2 [TIMP-2], transformation growth factor ß-1 [TGF-B1], and prostaglandin 2 [PGE2]) for adverse urodynamic features and for upper urinary tract damage in adult patients with spina bifida. MATERIALS AND METHODS: A single-center prospective trial was conducted from March 2015 to March 2017 including all consecutive adult patients with spina bifida seen for urodynamic testing. The urine was collected and stored at -80°C. A urodynamic and an upper urinary tract were systematically performed. At the end of the inclusion period, urines were defrosted and urinary nerve growth factor, BDNF, TIMP-2, and TGF-B1 were assessed using validated ELISA kits. The urinary markers levels were adjusted on the urinary creatinine level. Urinary MMP-2 levels were assessed by zymography. RESULTS: Fourty patients were included. Only TIMP-2 and MMP-2 were significantly associated with poor bladder compliance (P = .043 and P = .039, respectively). TIMP-2 was also the only urinary marker significantly associated with upper urinary tract damage on imaging (OR = 19.81; P = .02). Of all urodynamic parameters, bladder compliance and maximum detrusor pressure were the only ones associated with upper urinary tract damage on imaging (P = .01 and P = .02), The diagnostic performances of urinary TIMP-2 for upper urinary tract damage were slightly superior to PdetMax and bladder compliance with an area under the curve of 0.72. CONCLUSION: Urinary TIMP-2 and MMP-2 were significantly associated with poor bladder compliance and urinary TIMP-2 was significantly associated with upper urinary tract damage. These findings support a pathophysiological role of extracellular matrix remodeling in poor bladder compliance of adult patients with spina bifida.

Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study.

OBJECTIVE: The efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success. DESIGN: We performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort. RESULTS: From January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion. CONCLUSIONS: A successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT01183403; Results.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases.

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

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis.

OBJECTIVES: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn®) in this population. MATERIALS AND METHODS: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5-8 aphereses in a single induction series of ≤10 weeks. Endpoints included rates of remission (clinical activity index [CAI] ≤ 4) at weeks 24 and 48. RESULTS: Of 94 patients (ITT population), remission and response rates were 34.0% and 44.7% at week 24, and 33.0% and 39.4% at week 48. Among 30 patients with prior failure of IS and biologics, 33.3% and 20.0% were in remission at weeks 24 and 48. At both weeks, 19.2% of patients achieved steroid-free remission. Sustained remission or response occurred in 27.7% of patients at 48 weeks. The cumulative colectomy rate at week 96 was 23.4%. Safety was consistent with previous findings. CONCLUSIONS: This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.

Fecal incontinence in patients with spina bifida: The target is the rectum.

AIMS: The prevalence rate of severe fecal incontinence (FI) in adults with spina bifida (SB) is high. The physiological basis of FI in SB has not been clearly established, which contributes to inadequate care. The aim was to better characterize a large cohort of adults with special consideration of anorectal physiology. METHODS: A multidisciplinary team from a French referral centre for SB prospectively collected data on patients who had an anorectal manometry. Factors associated with severe FI (Cleveland clinical incontinence score ≥ 9) were assessed in a multivariate analysis model. RESULTS: A total of 132 adults with SB (sex ratio M/F: 55 [41.7%]/77 [58.3%]; mean age of 38.2 [11.6] years old) were assessed. Among these patients, 83/132 (62.9%) suffered from severe FI. Rectal perception was not evaluable among 17 patients who had a latex allergy. Overall, 29/115 (25.2%) had maximal tolerable volume (MTV) > 330 mL or no sensation. The absence of anal canal sensitivity, MVT > 330 mL and the amplitude of the recto-anal inhibitory reflex (RAIR) >75% after a rectal isovolumic inflation of 50 mL were significantly associated with severe FI in the multivariate analysis model. Neither neurological level nor other neurological features were associated with severe FI. CONCLUSIONS: This study showed that FI in patients with SB is mainly associated with rectal abnormalities. This should be taken into consideration to improve incontinence management of patients with SB.