Assessment of sexual dysfunction in patients with perianal Crohn's disease.

AIM: Over the past 10 years, several studies have focused on sexuality in patients with Crohn's disease. Very few of them specifically focused on perianal disease (PD). This study aimed to compare the prevalence of sexual dysfunction (SD) in Crohn's disease patients with active PD versus controls without active PD. METHOD: Patients from 14 French centres with active PD, defined by the presence of symptomatic ulceration, fistula or stenosis, were arbitrarily included. They were compared with controls from the existing SEXIA cohort. Men completed the International Index of Erectile Function (IIEF) and women the Female Sexual Function Index (FSFI). The primary end-point was SD defined by FSFI < 26.55 in women and IIEF < 42.9 in men. RESULTS: Ninety-seven patients (64 women, 33 men) and 238 controls (131 women, 107 men) were included. SD was found in 66% of the female patients versus 50% of the controls (P = 0.04). In the male population, SD was found in 30% of the cases versus 16% of the controls (P = 0.06). Erectile dysfunction affected 46% of the male patients and 43% of the controls (P = 0.8). On multivariate analysis, the predictive factor most strongly associated with SD in women was severely active anal PD defined by a perineal disease activity index > 4 [OR = 13.05 (2.32-73.44)]. CONCLUSION: Women with active PD had an increased prevalence of SD compared with controls without active PD. In the male population, the study was unable to determine whether there was a difference as it was underpowered.

How to manage anal ulcerations and anorectal stenosis in Crohn's disease: algorithm-based decision making : French National Working Group Consensus 2018.

The French National Society of Coloproctology established national recommendations for the treatment of anoperineal lesions associated with Crohn's disease. Treatment strategies for anal ulcerations and anorectal stenosis are suggested. Recommendations have been graded following international recommendations, and when absent professional agreement was established. For each situation, practical algorithms have been drawn.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Management of anoperineal lesions in Crohn's disease: a French National Society of Coloproctology national consensus.

The French National Society of Coloproctology established national recommendations for the treatment of anoperineal lesions associated with Crohn's disease. Treatment strategies for acute abscesses, active fistulas (active denovo and still active under treatment), fistulas in remission, and rectovaginal fistulas are suggested. Recommendations have been graded following the international recommendations, and when absent, professional agreement has been established. For each situation, practical algorithms have been drawn.

Deep ulcers are associated with increased C-reactive protein in active ulcerative colitis.

BACKGROUND: Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC). AIMS: To investigate the connection between CRP elevation and deep ulcers in UC. METHODS: Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019. RESULTS: Forty-one (9 (22%) with deep ulcers) patients were included in the prospective cohort: 4/5 (80%) patients with CRP > 100 mg/L, 2/10 (20%) patients with CRP between 30 and 100 mg/L and 3/26 (12%) patients with CRP < 30 mg/L had deep ulcers (p = 0.006). In the retrospective cohort [46 patients (31 (67%) with deep ulcers)], 14/14 (100%) patients with CRP > 100 mg/L, 11/17 (65%) patients with CRP between 30 and 100 mg/l and 6/15 (40%) patients with CRP < 30 mg/L had deep ulcers (p = 0.001). Positive predictive value of CRP > 100 mg/l for presence of deep ulcers was 80% and 100% in both cohorts, respectively. CONCLUSIONS: CRP elevation is a robust surrogate marker for presence of deep ulcers in UC. Elevated CRP or presence of deep ulcers could influence the choice of medical therapy in acute severe UC.

Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.

Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.

How to Manage Inflammatory Bowel Disease Patients When They Withdraw Anti-Tumour Necrosis Factor [Anti-TNF] Due to Severe Anti-TNF-Induced Skin Lesions? A Multicentre Cohort Study.

BACKGROUND AND AIMS: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect. METHODS: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation. RESULTS: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]. CONCLUSIONS: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse.

Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study.

INTRODUCTION: Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. METHODS: A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. RESULTS: Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. CONCLUSIONS: In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

Study of Helicobacter pullorum proinflammatory properties on human epithelial cells in vitro.

BACKGROUND AND AIMS: Helicobacter pullorum is an enterohepatic Helicobacter species of avian origin detected in patients with acute diarrhoea and inflammatory bowel disease. The aim of the present study was to determine whether H pullorum exerts a direct effect on human intestinal epithelial cells in vitro and to characterise the bacterial mechanisms and the signalling pathways involved. MATERIALS AND METHODS: The proinflammatory properties of H pullorum from human and avian origins were measured on human gastric (AGS) and intestinal (CaCo-2 and HT-29) epithelial cell lines after co-culture with different H pullorum strains, and the extent of nuclear factor-kappaB (NF-kappaB) involvement was determined. RESULTS: All of the H pullorum strains tested stimulated interleukin 8 (IL8) secretion by the three cell lines. Similar results were obtained with heat-killed H pullorum. Incubation of cells with filtered H pullorum culture supernatants did not stimulate IL8 secretion. The same observation was made when bacterial adherence was inhibited by Transwell inserts. H pullorum induced NF-kappaB activation and rapid nuclear translocation as demonstrated by immunofluorescent staining and cellular fractionation. NF-kappaB involvement was confirmed by using the specific inhibitor SN50 and small interfering RNA (siRNA) which abolished H pullorum-induced IL8 production. CONCLUSIONS: H pullorum strains stimulate IL8 secretion by human gastric and intestinal epithelial cell lines. This effect requires bacterial adherence and probably lipopolysaccharides, and is mediated by NF-kappaB signalling. The present study strengthens the argument that H pullorum is a potent human pathogen and highlights its putative role in acute and chronic digestive diseases such as inflammatory bowel disease.

Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients.

BACKGROUND AND AIMS: The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. METHODS: All UC patients undergoing SC were included. Postoperative complications according to ClavienDindo's classification, long term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. RESULTS: A TOTAL OF: 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], 'diverticulitis' [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median followup of 40 months, 24/69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. CONCLUSIONS: After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.

[The liver and methotrexate]. / Foie et méthotrexate.

Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.

Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with hemochromatosis: a prospective study.

BACKGROUND: The role of hepatic iron overload in the development of hepatic fibrosis in patients with hemochromatosis is well-established. Transient elastography (FibroScan) is a new noninvasive, rapid, reproducible bedside method, allowing assessment of liver fibrosis by measuring liver rigidity. OBJECTIVES: The aim of this prospective study was to evaluate liver fibrosis with FibroScan and other noninvasive biochemical methods in patients with hemochromatosis (C282Y homozygosity) compared with control patients. PATIENTS AND METHODS: From January 2004 through October 2006, all consecutive patients with hemochromatosis were evaluated for liver fibrosis using noninvasive methods (FibroScan and biochemical markers). These patients were compared with patients who had chronic cytolysis and no fibrosis on liver biopsy. RESULTS: One hundred and three consecutive patients (57 cases and 46 controls) were fully investigated. Median FibroScan values were similar in both groups, 5.20 kPa versus 4.9 kPa, respectively. No differences were observed between cases and controls for all biochemical markers. A strong correlation was observed between FibroScan and many biochemical markers, although ferritin levels did not correlate with FibroScan values. The prevalence of patients with FibroScan values greater than 7.1 kPa (cut-off level for significant fibrosis) was 22.8% in patients with hemochromatosis and 0% in the controls (P<0.0001). CONCLUSION: FibroScan and biochemical markers could be reliable noninvasive methods for detecting liver fibrosis in patients with hemochromatosis. Such patients have high FibroScan values more often than do control patients. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience.

BACKGROUND: Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM: To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS: Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION: In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.

Frequency of and Factors Associated With Sexual Dysfunction in Patients With Inflammatory Bowel Disease.

BACKGROUND: Improvement of quality of life is a main objective in inflammatory bowel disease [IBD] management. Data on sexual dysfunction [SD] in IBD are scarce. This study compared rates of SD between IBD patients and healthy controls [HC], and searched for predictors of SD. METHODS: All consecutive IBD patients seen in two tertiary centres during 2 months were invited to fill an anonymous validated questionnaire on their sexual function [Female Sexual Index Function and International Index of Erectile Function]. The same questionnaires were filled by HC and by patients with irritable bowel syndrome [IBS] enrolled as a second comparative group. RESULTS: In all, 358 IBD patients filled the questionnaire [192 women]-including 238 with Crohn's disease and 120 with ulcerative colitis-and 110 HC [54 women] and 107 IBS patients [54 women]. In women, SD rates were 53.6% in IBD vs 28% in HC [p < 0.01] and 77.5% in IBS [p = 0.10] patients; in men, figures were 16.9% in IBD, 7.4% in HC [p = 0.64], and 26.4% in IBS [p = 0.60]. An erectile dysfunction [ED] was reported by 43% of IBD patients, 13% of HC [p < 0.01] and 55% of IBS patients [p = 0.60 vs IBD]. Predictors of SD and ED were social and emotional functioning, anxiety in women and depression in men. IBD activity was not associated with SD. CONCLUSIONS: In IBD, 54% of women have an SD and 43% of men an ED. These rates are significantly higher than in HC, mostly driven by psychological factors, and independent from disease severity.

Endoscopic Detection of Small Bowel Dysplasia and Adenocarcinoma in Crohn's Disease: A Prospective Cohort-Study in High-Risk Patients.

BACKGROUND AND AIMS: Crohn's disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. METHODS: We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. RESULTS: In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. CONCLUSION: In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA.

Efficacy and safety of golimumab in Crohn's disease: a French national retrospective study.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents have improved the care of Crohn's disease (CD). After the first anti-TNF discontinuation, it is possible to switch to another anti-TNF. Three anti-TNF agents are available for ulcerative colitis (infliximab, adalimumab and golimumab), but only the first 2 have been approved for CD because golimumab has not been studied for this indication. AIM: To report the efficacy and safety of golimumab in CD. METHODS: Crohn's disease patients who received golimumab were identified in 12 French tertiary centres and were retrospectively analysed. The primary endpoint was the duration of golimumab treatment before escalation or discontinuation. The clinical response was defined as a decrease of more than 3 points in the Harvey-Bradshaw index or by global physician assessment. RESULTS: One hundred and fifteen patients were included. The golimumab treatment duration was 9.8 months (0.55-44), and 48.7% of the patients were still under treatment at the end of follow-up. Clinical response was observed in 55.8% of the patients after a mean duration of 3.8 months. The probability of remaining under treatment without escalation at 6, 12 and 24 months was 54.6%, 34.9% and 19.3% respectively. In multivariate analysis, discontinuation of the first anti-TNF agent due to intolerance (odds ratio, OR = 2.16; 95% CI, confidence interval [1.25-3.86]; P = .005) and co-immunosuppression for more than 6 months (OR = 3.98; 95% CI [2.3-7.1]; P < .0001) were predictive factors of efficacy. Six per cent of the patients discontinued treatment due to intolerance. CONCLUSION: After failure of infliximab or adalimumab for Crohn's disease, golimumab was safe and seemed beneficial in half of the patients.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

BACKGROUND: We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. AIMS: To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. METHODS: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 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 54. RESULTS: At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.

Diagnosis of liver fibrosis by transient elastography (FibroScan) and non-invasive methods in Crohn's disease patients treated with methotrexate.

BACKGROUND: Methotrexate is an effective treatment in Crohn's disease, which may induce liver fibrosis with high cumulative doses. Transient elastography (FibroScan, Echosens, Paris, France) is a new non-invasive rapid, allowing assessment of liver fibrosis by measurement of liver stiffness. AIM: A prospective study to evaluate liver fibrosis with FibroScan and non-invasive biochemical methods in Crohn's disease patients treated with methotrexate. METHODS: Consecutive Crohn's disease patients had evaluation of liver fibrosis with non-invasive methods. Two subgroups of patients were compared: cumulative dose of methotrexate of more than 1500 mg (group 1) and naive for methotrexate (group 2). Liver biopsy was performed in patients with persistent liver enzyme abnormalities or FibroScan value >8.7 kPa. RESULTS: Fifty-four consecutive Crohn's disease patients were fully investigated (45 females, mean age 41 +/- 14 years). Median FibroScan values were similar in group 1 (n = 21) and in group 2 (n = 33), 5.5 and 4.5 kPa, respectively. FibroScan values were not correlated with the cumulative dose of methotrexate. CONCLUSION: In Crohn's disease patients treated with a high dose of methotrexate, significant liver fibrosis is rare and not accurately detected with liver enzymes abnormalities. FibroScan could be recommended and liver biopsy could be performed only with patients with high values and/or with chronic liver enzymes abnormalities.