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.

Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors.

AIM: The medico-surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico-surgical strategies. METHOD: All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12-week follow-up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s). RESULTS: One hundred and sixty-nine patients were included. The median follow-up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter-sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13-5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38-127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11-12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model. CONCLUSION: Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.

Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

Protocol of a multicentric prospective cohort study for the VALIDation of the IBD-disk instrument for assessing disability in inflammatory bowel diseases: the VALIDate study.

BACKGROUND: Inflammatory Bowel Diseases (IBD) affect psychological, family, social and professional dimensions of patients' life, leading to disability which is essential to quantify as part of Patient-Reported Outcomes (PROs) newly included in the targets to reach in IBD patients. Up to now, the IBD-Disability Index (IBD-DI) was the only validated tool to assess disability, but it is not appropriate for use in clinical practice. The IBD Disk was developed, a shortened and self-administered tool, adapted from the IBD-DI, in order to give immediate representation of patient-reported disability. However, the IBD Disk has not been validated yet in clinical practice. The aims of the VALIDate study are to validate this tool in a large population of IBD patients and to compare it to the already validated IBD-DI. METHODS: The VALIDate study is an ongoing multicentric prospective cohort study launched in April 2018 in 3 French University Hospitals (Nantes, Rennes, Angers), with an objective to reach a sample of 400 patients over a period inclusion of 6 months. Each patient will fill in the two questionnaires IBD Disk and IBD-DI at baseline, then between 3 and 12 months later, during a follow-up visit. Clinical and socio-demographic data will also be collected. During these two consultations, gastroenterologists and patients will evaluate disease activity thanks to a semi-quantitative 4-grade scale, named respectively PGA (Physician Global Assessment) and PtGA (Patient Global Assessment). This cohort will allow to evaluate the validity of the IBD Disk with respect to the IBD-DI in order to generalize its use for clinical practice. Other psychometric criteria of the IBD Disk will also be analysed as its reliability or its discriminant capacity. Close attention will nonetheless be needed to minimize the number of lost to follow-up patients between baseline and follow-up. DISCUSSION: The VALIDate study is the study designed to validate the IBD Disk, a visual tool easily useable in daily practice to assess disability in IBD patients. The results of this trial should enable the diffusion of this tool. TRIAL REGISTRATION: The trial is registered in ClinicalTrials.Gov with registration number NCT03590639. First posted: July 18, 2018.

Chronic pelvic pain and rectal prolapse invite consideration of enterocele.

AIM: Data on the pathogenesis and symptoms of enterocele are limited. The objectives of this study were to determine the clinical phenotype of patients with enterocele, to highlight the main functional and/or anatomical associations and to improve the accuracy of the preoperative assessment of pelvic floor disorders. METHOD: A total of 588 patients who were referred to a tertiary unit for an anorectal complaint completed a self-administered questionnaire and underwent physical examination, anorectal manometry and defaecography. Using defaecography, enterocele was defined as a radiological hernia of the small bowel into an enlarged rectovaginal space. One hundred and thirty-five patients with enterocele were age- and gender-matched with 270 patients without enterocele. Factors associated with enterocele were assessed using univariate and multivariate analysis models. RESULTS: Patients with enterocele were less frequently obese than patients without enterocele (8/135 vs 36/270; P = 0.02) and more frequently had a past history of pelvic surgery (51/135 vs 75/270; P = 0.04). They complained more frequently of pelvic pain on bearing down (29/135 vs 24/270; P = 0.003), anal procidentia (37/135 vs 46/270; P = 0.01) and more frequently had irritable bowel syndrome (83/135 vs 131/270; P = 0.01) and severe constipation according to the Kess score (104/135 vs 182/270; P = 0.04). Anorectal function was comparable between the two groups. Patients with enterocele had more frequent rectoceles and overt rectal prolapses than patients without enterocele. CONCLUSIONS: Enterocele should be investigated in patients with chronic pelvic pain, overt rectal prolapse and/or a past history of pelvic surgery.

Online training on how to diagnose anoperineal lesions of Crohn's disease: Do pictures matter? A nationwide randomized study.

Any gastroenterologist must be trained to properly diagnose anoperineal lesions in patients with Crohn's disease (APLOC). The aim of this study was to establish whether adding pictures would improve teaching effectiveness of the diagnosis of APLOC to French gastroenterology trainees. METHOD: Trainees were asked to answer a first web-based survey consisting of evaluating 12 pictures of APLOC with a closed answer questionnaire. They were then randomized in 2 groups. Group A received an online teaching with typical pictures and APLOC definitions and group B definitions only. Trainees were asked again seven days later to answer a second survey with 12 other pictures of APLOC and 14 experts also answered this survey. Diagnostic scores were expressed in %. The primary endpoint was the comparison of the score of survey 2 between the two groups of trainees. Secondary endpoints were to compare results of survey 2 between trainees of both groups and experts, and assess diagnosis of each lesion. RESULTS: Two hundred fourty eight trainees among 465 answered survey 1, and 195 survey 2. The diagnostic score was 71.9% for groups A and B and 74.6% for experts (differences NS). After training diagnosis of ulceration was 72% for group A and 72.9% for group B, fistulae 85.2% versus 85.8%, erythema 44.1% vs. 55.6%, anoperineal scars 67.5% vs. 65.6%, and abscess 100% (differences NS). CONCLUSION: There was no difference between the two teaching methods. Further research should be performed aiming at improving teaching material and quotation baremes.

Sphincter-sparing surgery for complex anal fistulas: radiofrequency thermocoagulation of the tract is of no help.

AIM: To compare the rate of failure of radiofrequency thermocoagulation for anal fistula with that of rectal advancement flap in a case-matched study. METHOD: Patients who underwent radiofrequency treatment were compared with age- and sex-matched patients with Crohn's disease (CD) who underwent a rectal flap procedure. Fistula features, general characteristics and the main clinical events were recorded in a prospective database. Failure was defined by at least one of following: abscess, purulent discharge, visible external opening or further drainage procedure. RESULTS: A total of 62 patients [median age 45 (range 36.8-57.5) years; 22 women, 40 men; 22 with CD] were analysed. The failure rate of radiofrequency treatment was higher than that of rectal flap treatment (74.2% vs 32.2%; P = 0.004). The cumulative probabilities of failure of the radiofrequency treatment were 53.8% (38.8-68.3), 71.8% (55.3-84.0) and 87.4% (70.6-95.3) at 3, 6 and 12 months, respectively. Three patients in the radiofrequency group required drainage for an abscess and one had severe thermal ulceration. The Cox proportional hazards regression model (surgical procedure, obesity, CD) showed rectal flap treatment [3.48 (1.60-8.07); P = 0.001] and CD [2.60 (1.16-6.41); P = 0.02] to be the main independent predictors of healing. CONCLUSION: Radiofrequency thermocoagulation is a less satisfactory sphincter-sparing treatment for the management of anal fistula than a rectal flap procedure.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

AIM: Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. RESULTS: Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24 months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P = 0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. CONCLUSION: Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

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.

Anoperineal lesions in Crohn's disease: French recommendations for clinical practice.

BACKGROUND: Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn's disease (CD). Management should involve a multidisciplinary approach combining the knowledge of the gastroenterologist, the colorectal surgeon and the radiologist who have appropriate experience in this area. Given the low level of evidence of available medical and surgical strategies, the aim of this work was to establish a French expert consensus on management of anal Crohn's disease. These recommendations were led under the aegis of the Société Nationale Française de Colo-Proctologie (SNFCP). They report a consensus on the management of perianal Crohn's disease lesions, including fistulas, ulceration and anorectal stenosis and propose an appropriate treatment strategy, as well as sphincter-preserving and multidisciplinary management. METHODOLOGY: A panel of French gastroenterologists and colorectal surgeons with expertise in inflammatory bowel diseases reviewed the literature in order to provide practical management pathways for perianal CD. Analysis of the literature was made according to the recommendations of the Haute Autorité de Santé (HAS) to establish a level of proof for each publication and then to propose a rank of recommendation. When lack of factual data precluded ranking according to the HAS, proposals based on expert opinion were written. Therefore, once all the authors agreed on a consensual statement, it was then submitted to all the members of the SNFCP. As initial literature review stopped in December 2014, more recent European or international guidelines have been published since and were included in the analysis. RESULTS: MRI is recommended for complex secondary lesions, particularly after failure of previous medical and/or surgical treatments. For severe anal ulceration in Crohn's disease, maximal medical treatment with anti-TNF agent is recommended. After prolonged drainage of simple anal fistula by a flexible elastic loop or loosely tied seton, and after obtaining luminal and perineal remission by immunosuppressive therapy and/or anti-TNF agents, the surgical treatment options to be discussed are simple seton removal or injection of the fistula tract with biological glue. After prolonged loose-seton drainage of the complex anal fistula in Crohn's disease, and after obtaining luminal and perineal remission with anti-TNF ± immunosuppressive therapy, surgical treatment options are simple removal of seton and rectal advancement flap. Colostomy is indicated as a last option for severe APL, possibly associated with a proctectomy if there is refractory rectal involvement after failure of other medical and surgical treatments. The evaluation of anorectal stenosis of Crohn's disease (ARSCD) requires a physical examination, sometimes under anesthesia, plus endoscopy with biopsies and MRI to describe the stenosis itself, to identify associated inflammatory, infectious or dysplastic lesions, and to search for injury or fibrosis of the sphincter. Therapeutic strategy for ARSCD requires medical-surgical cooperation.

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.

[Children with inflammatory bowel disease: Assessment of the transition from the pediatric to the adult care unit]. / Évaluation de la transition pédiatrie-gastroentérologie d'adultes des enfants atteints de maladie inflammatoire cryptogénique intestinale.

AIM: Assess the transition of children followed for inflammatory bowel disease (IBD) to the adult gastroenterology care unit and the development of joint medical visits (JMVs). PATIENTS AND METHOD: This study was conducted at the Rennes University Hospital (Brittany, France). All patients with IBD and relayed to an adult gastroenterologist (GE) between 2000 and 2014 were included. The following medical data were collected: age, gender, clinical status, disease activity, type of follow-up (freelance or at hospital), medical history, disease locations, and treatments received. Patients who were relayed in the same hospital attended a JMV with both the pediatric and adult gastroenterologists. Patients and parents were interviewed with a questionnaire sent by mail. They were asked how they had perceived the transition with questionnaires containing specific items about the JMV. The answers of the patients who attended JMVs were compared to those who did not attend. RESULTS: Eighty-two patients were included. The patient response rate was 56 % (parents, 59 %). The average age at transition was 18±0.8years. Fifty patients were relayed in the same hospital with 30 attending a JMV. These patients suffered from more severe disease than other patients. Thirty-nine patients felt ready to transition (87 %). The JMV was deemed beneficial or very beneficial (74 %) for both follow-up and the benefits of the GE's knowledge of the medical file. The parents' responses did not differ from the patients'. CONCLUSION: Development of the JMV enables a successful transition for pediatric patients with IBD. It could be improved by developing specific therapeutic education sessions based on transition training.

Pathophysiology of fecal incontinence in obese patients: A prospective case-matched study of 201 patients.

BACKGROUND: Obesity is an emerging risk factor for fecal incontinence (FI). The aim of this study was to characterize pathophysiologic mechanisms of FI in obese patients compared with non-obese patients in a prospective case-matched study. METHODS: The general characteristics and data of the anorectal manometry and endosonography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by a Cleveland Clinic Incontinence Score (CCIS) >4. Obesity was defined by a body mass index ≥30 kg/m2 . Obese patients were case-matched with two age- and sex-matched non-obese patients. KEY RESULTS: A total of 201 patients were included (67 obese matched with 134 non-obese). The CCIS, Knowles-Eccersley-Scott Symptom Constipation Score and quality of life score were comparable between obese and non-obese patients with FI. Factors significantly associated with obesity in FI patients were cholecystectomy (odds ratio [OR]=3.45 [1.19-10.32], P=.0230), irritable bowel syndrome - diarrhea (OR=2.94 [1.22-7.19], P=.0158), upper part of the anal canal resting pressure ≥22 mm Hg (OR=3.45 [1.45-8.76], P=.0045), maximum rectal tolerable volume ≥240 mL (OR=3.14 [1.34-7.54], P=.0082), and abdominal pressure ≥28 mm Hg (OR=2.75 [1.13-7.33], P=.0248) by multivariate analysis. CONCLUSIONS & INFERENCES: Obese patients with FI had a comparable severity of FI to that of non-obese patients with FI. Regarding obesity in patients with FI, physicians should focus on stool consistency.

Prospective cohort study of phenotypic variation based on an anal sphincter function in adults with fecal incontinence.

BACKGROUND: One-third of patients with fecal incontinence (FI) do not have any anal dysfunction. The aim was to characterize patients with FI with normal anal function compared with patients with anal weakness. METHODS: The general characteristics and data of anal manometry, endosonography, and defecography of patients who were evaluated for FI at a single institution from 2005 to 2015 were prospectively assessed. Fecal incontinence was defined by the Cleveland Clinic Incontinence Score (CCIS) >4. Anal weakness was defined by one or more of the three following parameters: <25 mmHg at the upper part of the anal canal, <26 mmHg at the lower part of the anal canal, and <60 mmHg for the mean squeeze pressure. KEY RESULTS: A total of 439 patients with FI were included (152 with normal anal function/287 with anal weakness). Severe constipation (Kess score ≥21) was predominant in patients with normal anal function (44/151 vs 50/284, respectively; p = 0.0054). Fecal incontinence with normal anal function was significantly associated with lower age (>63 years; odds ratio [OR] = 0.29), higher weight (>65 kg; OR = 1.69), fecal urgency (OR = 1.58), less severe FI score (CCIS score >10; OR = 0.52), higher abdominal pressure (>36 mmHg; OR = 2.15), and paradoxical puborectal contraction (OR = 2.07) in a multivariate analysis model. CONCLUSION & INFERENCES: Fecal incontinence with normal anal function is a specific phenotype that involves distal constipation and may be an early stage of FI with anal weakness. Physicians should adapt their management to focus on the treatment of constipation.

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.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Anorectal dysfunction in patients with ulcerative colitis: impaired adaptation or enhanced perception?

BACKGROUND: Rectal disorders during ulcerative colitis (UC) drastically alter the quality of life and may result from an impairment of rectal perception and compliance. This study aims to assess anorectal disorders in patients with mild-to-moderate UC. METHODS: Anal pressures and the rectal responses to phasic rectal isobaric distension in 10 patients with mild-to-moderate UC were prospectively compared with those in 10 healthy volunteers (HVs). KEY RESULTS: The patients in each group were similar regarding age, gender, and delivery. In the resting state, the anal canal pressures were similar between the groups. Only the squeeze pressures of the lower anal canal were significantly lower in UC patients than in HVs. During phasic isobaric distension, rectal sensitivity was similar between the groups, whatever the step of distension. Isobaric rectal distension resulted in a significant decrease of the rectoanal inhibitory reflex and a decrease in rectal tone and a significant drop in rectal compliance in UC patients compared with HVs. CONCLUSIONS & INFERENCES: Patients showing mild-to-moderate UC experience rectal compliance and innervation disorders without a significant change in rectal sensitivity. The findings of this work suggest impairment not only of the properties of the rectal wall but also of intrinsic innervation. Repeated evaluation over time may be helpful for analyzing the reversibility of the process after healing.

Efficacy of sustained combination therapy for at least 6 months with thiopurines and infliximab in patients with ulcerative colitis in clinical remission: a retrospective multicenter French experience.

BACKGROUND AND AIMS: Long-term benefits of combination therapy (combotherapy) with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative colitis (UC) than in Crohn's disease. The aim of the present study was to determine UC disease activity in patients who received at least 6 months of combotherapy, and whether cotreatment for more than 6 months was useful in these patients. METHODS: A retrospective multicenter study was conducted in seven French academic centers from January 2010 to September 2012, including all UC patients having received at least 6 months of combotherapy in prolonged remission off steroids. During the follow-up period, which was divided into trimesters, scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment of UC activity by trimester was based on the following events: disease relapse defined by clinical relapse requiring a change of treatment, IFX failure, and colectomy. RESULTS: Eighty-two patients were included (mean age 38 years; male:female ratio 1:1) and followed up for a median of 22.3±14.0 months. Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer clinical relapses were observed with combotherapy (p = 0.049). Similar results were observed for IFX failure (p = 0.048). No difference was observed for colectomy. Duration of combotherapy longer than 9 months was inversely associated with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70]). CONCLUSIONS: UC patients treated with combotherapy should maintain IFX and AZA for at least 9 months. Further studies are required to determine the optimal duration of combotherapy before stopping AZA in this situation.