What is the outcome for patients undergoing more than two ileocolonic resections for recurrent Crohn's disease? A comparative study of 569 consecutive procedures.

AIM: To assess the outcome for patients undergoing repeated ileocolonic resection for recurrent Crohn's disease (CD). METHOD: All patients undergoing ileocolonic resection for terminal ileal CD between 1998 and 2016 in our tertiary care centre were retrospectively reviewed. RESULTS: Between 1998 and 2016, 569 ileocolonic resections were performed for CD: 403 of these were primary resections (1R, 71%), 107 second resections (2R, 19%) and 59 were third (or more) resections (> 2R, 10%). The laparoscopic approach rate was significantly less in the > 2R group (20/59, 34%) compared with the 2R (71/107, 66%; P = 0.002) and 1R (366/403, 91%) groups. However, conversion to an open approach did not show any difference between the three groups [1R group 46/366 (13%) vs 2R group 14/71 (20%) vs > 2R group 3/20 (15%); 1R vs > 2R P = 0.750; 2R vs > 2R P = 0.633]. Postoperative morbidity was significantly increased in the > 2R (28/59, 52%) group compared with the 1R group (115/403, 29%; P < 0.001) but showed no difference compared with the 2R group (43/107, 40%; P = 0.365). There was no difference between the groups in the incidence of severe postoperative morbidity (Clavien-Dindo ≥ 3) [1R group n = 24 (6%); 2R group n = 6 (6%); > 2R group n = 4, 7%; 1R vs > 2R P = 0.865, 2R vs > 2R P = 0.761]. CONCLUSION: Although the overall morbidity rate was higher, repeated surgery for recurrent CD in patients undergoing three or more ileocolonic resections was not associated with an increased risk of severe postoperative morbidity in our series.

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.

Is abdominal CT useful for the management of patients with severe acute colitis complicating inflammatory bowel disease? A study in 54 consecutive patients.

AIM: To evaluate the contribution of CT for the management of patients with severe acute exacerbation of colitis (SAC) complicating inflammatory bowel disease (IBD); in particular, its contribution to surgical decision making. METHOD: All patients who were admitted to our institution for SAC complicating IBD were divided into two groups: group A (those who received surgical treatment); and group B (those who received medical treatment). Admission CT results were compared between groups. RESULTS: From 2006 to 2015, 54 patients [26 male; median age 39 (17-71) years] presenting with SAC were placed in either group A (n = 41; 76%) or group B (n = 13; 24%). Surgical patients in group A more frequently had altered general status (50 vs 17%; P = 0.01). Physical examination, Lichtiger score, endoscopic findings and laboratory results were similar between the groups. There was no significant difference in CT data between the groups with respect to extent of the colitis (pan-colitis in 54 and 69%, respectively, P = 0.35), median colonic thickness [10 (4-16) vs 8 (6-11) mm, P = 0.15], target enhancement (88 vs 77%, P = 0.38) and occurrence of toxic megacolon (2 vs 0%). CONCLUSION: Admission CT is not helpful in surgical decision making in SAC.

Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery.

OBJECTIVES: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial. DESIGN: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis. RESULTS: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/ß Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence. CONCLUSIONS: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.

Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. METHODS: Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. RESULTS: Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P < 0·001). Fifteen of 232 patients who underwent colectomy for UC had previously had an appendicectomy, and nine of these had colonic cancer or HGD. Thirty (13·8 per cent) of 217 patients with the appendix in situ had colonic neoplastic lesions. Multivariable analysis showed that previous appendicectomy was associated with colorectal neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69). CONCLUSION: Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of appendicectomy represent a small subset, they may need closer monitoring for colorectal neoplasia.

Accuracy of computed tomographic colonography in a nationwide multicentre trial, and its relation to radiologist expertise.

OBJECTIVE: Reports on the accuracy of computed tomographic colonography (CTC) mainly involve series from expert institutions. The aims of this study were to assess CTC accuracy in a nationwide population and to relate it to radiologist performance in their initial training. DESIGN: Nationwide multicentre trial. SETTING: Twenty-eight radiologists, working in 26 mostly academic clinical units, were involved in the study after having attended a formal specialised 2-day training session on CTC. They worked through a training set of 52 cases with automatic feedback after an attempt at each case. PATIENTS: The study enrolled 845 patients with average and high risk of colorectal cancer, 737 of whom had both complete CTC and videocolonoscopy data, which constituted the dataset. INTERVENTIONS: Patients underwent same-day CTC followed by videocolonoscopy with segmental unblinding of CTC results. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive and negative predictive values for detection of polyps ≥ 6 mm in per-patient and per-lesion analyses of CTC without computer-aided detection. RESULTS: Sensitivity, specificity and positive and negative predictive values for patients with polyps ≥ 6 mm were 69% (95% CI 61% to 77%), 91% (95% CI 89% to 94%), 67% (95% CI 59% to 74%) and 92% (95% CI 90% to 94%), respectively. Univariate analysis showed that the detection rate for polyps ≥ 6 mm was linked to neither radiologist case volume nor number of polyps, but was related to sensitivity achieved in the training set. Pooled sensitivity was 72% (95% CI 63% to 80%) versus 51% (95% CI 40% to 60%) for radiologists achieving above and below median sensitivity in the training set (61%), respectively. Multivariate analysis showed that sensitivity for polyps ≥ 6 mm in the training set was the only remaining significant predictive factor for subsequent performance. CONCLUSIONS: Radiologist sensitivity CTC for detection of polyps ≥ 6 mm in training was the sole independent predictor for subsequent sensitivity in detection of such polyps.

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.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

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.

Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease.

BACKGROUND AND AIMS: A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn's disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence. METHODS: All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisière Hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow-up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within 2 years postsurgery. The proximal resection margin was analysed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for caecal carcinoma served as controls. RESULTS: Data were available from 171 postoperative follow-up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with postoperative recurrence were active smoking (hazard ratio (HR) = 1.94; 95% CI 1.06 to 3.60; p = 0.033), submucosal plexitis with >or=3 mastocytes (HR = 1.87; 95% CI 1.00 to 3.46; p = 0.048) and a disease-free resection margin <5 cm (HR = 0.52; 95% CI 0.27 to 1.02; p = 0.059). CONCLUSIONS: Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatment strategies in the immediate postoperative period.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Adalimumab for patients with Crohn's disease complicated by intra-abdominal abscess: a multicentre, prospective, observational cohort study.

doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section.

[Chronic intestinal pseudo-obstruction and anti-Hu syndrome: 13 years of follow-up without neoplasia]. / Pseudo-obstruction intestinale chronique et syndrome des anti-Hu: 13 ans de suivi sans apparition de néoplasie.

Chronic intestinal pseudo-obstruction (CIPO) is a heterogeneous group of rare disorders characterised by symptoms of intestinal obstruction with no mechanical evidence of obstruction. It is caused by ineffective intestinal contractions due to visceral neuropathy and/or neuropathy. In adults, CIPO is mostly secondary. The most common causes are metabolic disorders, connective tissue disorders, neuropathic drug related injuries, paraneoplasic and post-infectious syndromes and amyloidosis. Secondary forms of CIPO have been reported with anti-Hu antibodies. This corresponds to an antineuronal antibody that recognizes a protein expressed in the nuclei of neuron (ANNA-1) and neoplasic cells. The anti-Hu antibody must be searched for in patients over 40 years old with CIPO (associated with small cell lung cancer in 75% of cases). Recently, the association of CIPO and the anti-Hu antibody has been described without associated neoplasia. We report a case of an association of CIPO and anti-Hu antibody without cancer after 13 years of follow-up.

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.

An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease.

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

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.

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.

Three-stage Laparoscopic Ileal Pouch-anal Anastomosis Is the Best Approach for High-risk Patients with Inflammatory Bowel Disease: An Analysis of 185 Consecutive Patients.

BACKGROUND: There are very few studies and no consensus concerning the choice between two- and three-stage ileal pouch-anal anastomosis [IPAA] in inflammatory bowel diseases [IBD]. This study aimed to compare operative results between both surgical procedures. METHODS: Only patients who underwent a laparoscopic IPAA for IBD were included. They were divided into two groups: two-stage [IPAA and stoma closure] [Group A] and three-stage IPAA [subtotal colectomy, IPAA, stoma closure] [Group B]. RESULTS: From 2000 to 2015, 185 patients (107 men, median age of 42 [range, 15-78] years) were divided into Groups A [n = 82] and B [n = 103]. Patients in Group B were younger than in Group A (39 [15-78] vs 43 [16-74] years; p = 0.019), presented more frequently with Crohn's disease [16% vs 5%; p < 0.04], and were more frequently operated in emergency for acute colitis [37% vs 1%; p < 0.0001]. Cumulative operative time and length of stay were significantly longer in Group B (580 [300-900] min, and 19 [13-60] days) than in Group A (290 [145-490] min and 10 [7-47] days; p < 0.0001). Cumulative postoperative morbidity, delay for stoma closure, and function were similar between the two groups. Long-term morbidity was similar between Group A [13%] and Group B [21%; p = 0.18]. CONCLUSIONS: Our study suggested that postoperative morbidity was similar between two- and three-stage laparoscopic IPAA. It suggested that the three-stage procedure is probably safer for high-risk patients [ie in acute colitis].

Fistula Plug in Fistulising Ano-Perineal Crohn's Disease: a Randomised Controlled Trial.

BACKGROUND AND AIMS: Anal fistula plug [AFP] is a bioabsorbable bioprosthesis used in ano-perineal fistula treatment. We aimed to assess efficacy and safety of AFP in fistulising ano-perineal Crohn's disease [FAP-CD]. METHODS: In a multicentre, open-label, randomised controlled trial we compared seton removal alone [control group] with AFP insertion [AFP group] in 106 Crohn's disease patients with non- or mildly active disease having at least one ano-perineal fistula tract drained for more than 1 month. Patients with abscess [collection ≥ 3mm on magnetic resonance imaging or recto-vaginal fistulas were excluded. Randomisation was stratified in simple or complex fistulas according to AGA classification. Primary end point was fistula closure at Week 12. RESULTS: In all, 54 patients were randomised to AFP group [control group 52]. Median fistula duration was 23 [10-53] months. Median Crohn's Disease Activity Index at baseline was 81 [45-135]. Fistula closure at Week 12 was achieved in 31.5% patients in the AFP group and in 23.1 % in the control group (relative risk [RR] stratified on AGA classification: 1.31; 95% confidence interval: 0.59-4.02; p = 0.19). No interaction in treatment effect with complexity stratum was found; 33.3% of patients with complex fistula and 30.8% of patients with simple fistula closed the tracts after AFP, as compared with 15.4% and 25.6% in controls, respectively [RR of success = 2.17 in complex fistula vs RR = 1.20 in simple fistula; p = 0.45]. Concerning safety, at Week 12, 17 patients developed at least one adverse event in the AFP group vs 8 in the controls [p = 0.07]. CONCLUSION: AFP is not more effective than seton removal alone to achieve FAP-CD closure.