R. L. West

Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn’s disease

Backgroundu2002 Adalimumab is an effective treatment in patients with Crohn’s disease; as it is a humanized anti‐tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance.

Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: A double-blind placebo-controlled study

Background :u2002Ciprofloxacin is effective in perianal Crohns disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy.

Predictors of dose escalation of adalimumab in a prospective cohort of Crohn's disease patients.

Backgroundu2002 Adalimumab is effective for the induction and maintenance of remission in Crohn’s disease (CD)‐patients.

Perianal Fistulas in Crohn’s Disease Are Predominantly Colonized by Skin Flora: Implications for Antibiotic Treatment?

In this study we aimed to determine the microorganisms found in perianal fistulas in Crohn’s disease and whether treatment with ciprofloxacin affects these microorganisms. Thirteen patients (males/females, 7/6; median age, 34 years; range, 18–61 years) with fistulas were treated with infliximab, 5 mg/kg intravenously, at weeks 6, 8, and 12 and randomized to double-blind treatment with ciprofloxacin, 500 mg bd (n = 6), or placebo (n = 7) for 12 weeks. Samples were taken at baseline and at weeks 6 and 18. In the ciprofloxacin group 10 different genera of microorganisms were identified, while 13 genera could be identified in the placebo group. Gram-negative enteric floras were present in a small minority. The genera found in patients with perianal fistulas were predominantly gram-positive microorganisms. Therefore, antimicrobial treatment should be directed toward these microorganisms.

The ACCURE-trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicenter trial (NTR2883) and the ACCURE-UK trial: a randomised external pilot trial (ISRCTN56523019)

BackgroundOver the past 20xa0years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment.Methods/DesignThese paired phase III multicenter prospective randomised studies will include patients over 18xa0years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12xa0months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12xa0months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm.DiscussionThe ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course.Trial registrationNTR2883; ISRCTN56523019

Multimodal treatment of perianal fistulas in Crohn’s disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial

BackgroundCurrently there is no guideline for the treatment of patients with Crohn’s disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs.Methods/DesignThis is a multicentre, randomized controlled trial. Patients with Crohn’s disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs.DiscussionThe PISA trial is a multicentre, randomised controlled trial of patients with Crohn’s disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters.Trial registrationNederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).

Adalimumab in Crohn's disease patients: pharmacokinetics in the first 6 months of treatment

Adalimumab is an effective therapy for Crohns disease patients. However, there is limited knowledge on the pharmacokinetic properties of adalilumab in patients with Crohns disease.

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial

BACKGROUNDnTreatment of patients with ileocaecal Crohns disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life.nnnMETHODSnIn this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohns disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohns disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150).nnnFINDINGSnBetween May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF.nnnINTERPRETATIONnLaparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohns disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy.nnnFUNDINGnNetherlands Organisation for Health Research and Development.

P633 Decision-making, counselling and course of pregnancy in female inflammatory bowel disease patients

Background: An epidemiological association implicating diet in Inflammatory Bowel Disease (IBD) risk or protection is widely accepted. Despite unprecedented advances in aetio-pathogenesis, nutritional research has been limited by heterogeneity of study design, variability of diet, and difficulty in obtaining accurate longitudinal dietary data. Patients with IBD often make links to diet in clinical consultations, but there is a dearth of literature exploring dietary perceptions and practices in an IBD population [1]. The aim of the study was to evaluate dietary beliefs and behaviours in patients with IBD. Methods: We developed a 25-item questionnaire assessing demographics, dietary beliefs and habits, impact on social life and patients’ use of resources for dietary advice. The questionnaire was prospectively administered to consecutive IBD patients attending our IBD clinics from September to November 2013. Results: A total of 187 patients participated in the study. The average age was 48 years; 55% were female and 85% Caucasian. The median disease duration was 6 years. Thirty-nine percent had Crohn’s Disease and 52% had Ulcerative Colitis. Of the respondents, 49% felt that diet could be the initiating factor in IBD and 58% felt it could trigger a flare. Fifty-nine percent reported a modification in their diet and 38% reported taking dietary supplements. Worsening of symptoms with certain food and drinks was reported by 62%, the commonest being spicy food (46%), fatty food (33%) and alcohol (22%). A minority (17%) reported improvement in symptoms with certain foods and 66% deprived themselves of certain foods to prevent relapse with 24% refusing to dine outside of home for fear of causing relapse. Seventy-four percent of respondents believed that IBD affects appetite. On a visual analogue scale of 1 10, mean scores for appetite in disease remission and during disease relapse were 8 (SD 2.0) and 4 (SD 2.9) respectively (p = 0.001). Nearly half of respondents (47%) had never received any formal dietary advice, and most (67%) requested further dietary advice from dieticians (43%), nurses (34%) and patient information leaflets (28%). Conclusions: Patients express a belief that diet affects IBD symptoms and disease activity, with a high level of consistency around key perceived triggers. Whether all the symptoms reported are due to active inflammation cannot be ascertained, but the potential exists for dietary components triggering active disease and perpetuating gut injury, impacting on quality of life and health care costs. This should serve as an impetus for further patient centered research.

P598 Adalimumab trough levels in a prospective cohort of Crohn's disease patients

managements were similar in all treatment groups. The children remained in the study until recovery from diarrhea but up to a maximum of 7 days. Stool weight and duration of diarrhea were the primary outcomes. Results: Baseline clinical characteristics of the children are comparable between the groups. There is a trend in stool weight reduction in the groups receiving L-isoleucine and L-arginine alone or in combination and the reduction is significant on day 1(data presented in Table ). Also similar trend of reduction of duration of diarrhea was observed in those groups although the reduction was not statistically significant (combined analysis). Conclusion: L-isoleucine and L-arginine supplemented food help recovery by reducing stool weight and duration of diarrhea in children with acute diarrhea. Further large study is warranted to establish the beneficial effect of L-isoleucine and L-arginine supplemented food. Comparison of outcome variable (Data are Median, range