Crohn's Perianal Fistulas Research Articles

P653 Ligation of the intersphincteric fistula tract vs. endorectal advancement flap for high perianal fistulas in Crohn’s disease: a retrospective cohort study

The ligation of the intersphincteric fistula tract (LIFT) and advancement flap (AF) procedures are well-established, sphincter preserving procedures, for closure of high perianal fistulas. As surgical closure is not commonly offered in patients with Crohn’s fistulas, long-term data are limited. The aim of this study was to compare outcomes after both procedures in Crohn’s patients. In this retrospective cohort study, all consecutive Crohn’s patients ≥18 years treated with LIFT or AF between 2007 and February 2018 were included. Primary outcome was clinical healing defined as closure of external fistula opening without discharge. Secondary outcomes included radiological healing evaluated by MRI, recurrence, newly developed postoperative incontinence, prospective Vaizey Incontinence Score and global subjective change in continence (improved, unchanged or deteriorated). A clinical minimally important difference (MID) for improvement in the Vaizey Incontinence Score was determined using a clinical anchor-based method to assess the clinical relevance of changes in this score. Forty procedures in 37 patients (35.1% male, median age 33.9, LIFT: 19, AF: 21) were included. A non-significant trend was seen towards higher clinical healing percentages after LIFT compared with AF (89.5% vs. 60.0%; p = 0.065). The overall radiological healing and recurrence rates were not significantly different between LIFT and AF (52.6% vs. 47.6%; p = 0.752, 21.1% vs. 19.0%; P>0.999, respectively). In AF a trend was seen towards higher clinical healing percentages after anti-TNF/immunomodulator use (75.0% vs. 37.5%; p = 0.104). Newly developed postoperative incontinence was not significantly different (LIFT: 15.8% vs. AF: 21.4%; P>0.999). Interestingly, 22.2% had improved continence postoperatively (LIFT: 31.6% vs. AF: 11.8%; p = 0.236), and the global change question demonstrated improved continence in 47.4% (LIFT: 52.9% vs. AF: 42.9%; p = 0.612). The mean total Vaizey score prior to surgery, was 6.8 (SD 4.8) and after surgery this decreased to 5.3 (SD 5.0) (p = 0.067). The MID was calculated to be 2.92 and five patients with a deteriorated continence, all after AF (23.8%), reported a difference of more than 2.92 points and were therefore clinically relevant. In Crohn’s high-perianal fistulas the clinical and radiological healing, recurrence and incontinence rates are not significantly different between LIFT and AF. However, clinical healing rates seem higher after LIFT, and incontinence rates seem lower. Furthermore, the global change question demonstrated that the majority of patients actually benefitted from surgical intervention with respect to continence.

Treatment of Perianal Fistulas in Crohn's Disease, Seton versus Anti-TNF versus Surgical Closure Following Anti-TNF (PISA): A Randomised Controlled Trial

Background: Most patients with perianal Crohn's disease fistulas receive medical treatment with anti-TNF. So far, outcomes of anti-TNF have not been directly compared to chronic seton drainage or surgical closure. We hypothesized that chronic seton drainage would result in fewer re-interventions compared to anti-TNF and surgical closure. Methods: This multicentre, randomised trial was performed in 19 European centres. Patients with high perianal Crohn's fistulas with a single internal opening were randomly assigned in a 1:1:1 ratio to chronic seton drainage, long-term anti-TNF therapy, or surgical closure using a central web-based system without stratification. Patients were analysed according to the intention-to-treat principle. The primary outcome was the cumulative number of patients with fistula-related re-intervention(s) at 1.5 year. Patients refusing randomisation due to a specific treatment preference were included in a parallel prospective PISA registry cohort. Findings: Between September 14, 2013 and November 20, 2017, 44 of the 126 planned patients were randomised. The study was stopped by the data safety monitoring board because of futility. Seton treatment was associated with the highest re-intervention rate (10/15, versus 6/15 anti-TNF and 3/14 surgical closure patients, P = 0·02). No substantial differences in perianal disease activity and quality of life between the three treatment groups were observed. Interestingly, in the PISA prospective registry (n = 50), inferiority of chronic seton treatment was not observed for any outcome measure. Interpretation: The results imply that chronic seton treatment should not be recommended as the sole or superior treatment for perianal Crohn's fistulas. However, the statistical inferiority of seton treatment should be interpreted with caution, due to the crucial aspects of small numbers and as this inferiority could not be confirmed in the PISA registry data. Trial Registration Number: The trial is registered with the Dutch Trialregister.nl number NTR4137. Funding Statement: The Netherlands Organization for Health Research and Development and the Crohn and Colitis Foundation. Declaration of Interests: KAW, EJdG, MES, MGD, MFG, JMJ, AP, SAvT, DDZ, KFB, JvdB, MWM, WAB, and CJB have no conflicts of interests to declare. GRD’H has served as advisor for Abbvie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Echo Pharmaceuticals, Eli Lilly, Engene, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts and Vifor. CYP has served as adviser for Abbvie, Takeda, and Pliant, declares a grant from Takeda, and received speaker’s fees from Abbvie, Tillotts, and Takeda. KBG has served as speaker and/or advisor for Amgen, AbbVie, Biogen, Boehringer Ingelheim, Ferring, Hospira, MSD, Pfizer, Samsung Bioepis, Sandoz, Takeda and Tigenix. AS has served as speaker and/or advisor for Takeda. SD has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma, and Vifor. Ethics Approval Statement: The study was performed in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines, and is reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. The trial received central approval from the medical ethics committee at the Amsterdam UMC, location AMC, and from the corresponding committees in all participating centres.

Darvadstrocel for the treatment of patients with perianal fistulas in Crohn's disease.

Despite significant advances in medical and surgical therapy for perianal fistulas in Crohn's disease (CD), treatment results are still modest, and a specific need for more effective therapies is a reality. Darvadstrocel is composed of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue and constitutes the first stem cell therapy for perianal fistulizing CD to receive approval from the European Medicines Agency (EMA). This therapy is injected in both internal and external openings, as well as inside the fistula tracks, to induce fistula healing. In this monograph, the authors review the preclinical pharmacology of darvadstrocel, as well as pharmacokinetics and metabolism, and cover the main indications and detailed information on the efficacy and safety profile of the agent. Possible interactions with other agents used to treat CD are also explored. Darvadstrocel is a safe and effective therapy for perianal complex fistulas in CD, and represents the beginning of a new era of mesenchymal stem cell therapy in this difficult phenotype of the disease.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in Crohn’s disease (HOT-TOPIC): study protocol of a prospective interventional cohort study with one-year follow-up

Perianal fistulizing Crohn's disease (pCD) has a significant impact on patients' health and quality of life. Current treatment options have a relatively low success rate and a high recurrence risk. Positive effects of hyperbaric oxygen (HBO2) therapy have been indicated in animal studies as well as in small case series. This is a non-randomized, controlled pilot study. A total of 20 patients with pCD who have been refractory to standard therapy for at least six months will be included. Patients with a seton and stable treatment regimen will be included. Patients with anal strictures, rectovaginal fistulas, stoma or deep ulceration of the rectum will be excluded. Patients who are eligible but refuse HBO2 will be asked to serve as controls. Patients in the HBO2 group will be treated with 40 sessions of HBO2 therapy at 243-253 kPa, with the seton being removed after 30 sessions. Co-primary endpoints are changes in the perianal disease activity index and MRI-scores. Secondary outcomes are fistula drainage assessment, laboratory findings and patient-reported outcomes. Assessment will be done at baseline, 16 weeks, 34 weeks and 60 weeks after finishing HBO2. The aim of this study is to investigate the feasibility and therapeutic effect of HBO2 on pCD. The one-year follow-up should provide information on the effect durability. A comparison between patients treated with HBO2 and patients who continue to receive standard care will be made. The risk of bias will be limited by using clearly defined inclusion and exclusion criteria, baseline characteristics and consecutive recruitment of patients through an outpatient fistula clinic. The HOT-TOPIC trial has been approved by the local Medical Ethical Committee of the Academic Medical Centre in Amsterdam, the Netherlands. The trial has been registered at the Netherlands Trial Register (www.trialregister.nl), registration number: NTR 6676. Protocol version: August 2017, version 3.0.

Burden and outcomes for complex perianal fistulas in Crohn's disease: Systematic review.

AIMTo systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn’s disease (CD) patients with complex perianal fistulas.METHODSPubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016).RESULTSOf 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSIONComplex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

Mesenchymal Stromal Cells in the Treatment of Perianal Fistulas in Crohn'S Disease

Significant unmet needs remain in patients with Crohn's disease and perianal fistulas. Mesenchymal stromal cells have potent immunomodulatory actions. The Phase II studies reported efficacy of local injection of mesenchymal stromal cells to achieve closure of fistulas. A Phase III trial demonstrated that in patients with Crohn's disease and refractory complex perianal fistulas, a single injection of 120×106 cells was superior to local injection of placebo associated with the same surgical procedure, in obtaining closure of the fistula tracts together with absence of abscesses>2cm, 24 weeks after the injection, a stringent combined primary end point. The benefit over placebo was sustained 52 weeks after the single injection. The therapy is safe with adverse events limited to local pain.

Significant Medical and Surgical Morbidity in Perianal Crohn's Disease: Results from a Territory-Wide Study.

The presence of perianal fistulas in Crohn's disease [CD] denotes increased disease aggressiveness. We studied the epidemiology and clinical outcomes of perianal CD [PCD] using the Hong Kong territory-wide IBD Registry [HKIBDR]. Consecutive patients with PCD were identified from the HKIBDR, and disease characteristics, treatments, and outcomes were analysed. The risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. Among 981 patients with CD with 10530 patient-years of follow-up, 283 [28.8%] had perianal involvement, of which 120 [42.4%] were as first presentation. The mean age at diagnosis of PCD was 29.1 years, and 78.8% were male. The median follow-up duration was 106 months (interquartile range [IQR]: 65-161 months]. Perianal fistula [84.8%] and perianal abscess [52.7%] were the two commonest forms. Male, younger age at diagnosis of CD, and penetrating phenotypes were associated with development of PCD in multivariate analysis. Of 242 patients with fistulizing PCD, 70 [29.2%] required ≥5 courses of antibiotics, and 98 [40.5%] had ≥2 surgical procedures. Nine patients required defunctioning surgery and 4 required proctectomy. Eighty-four patients [34.7%] received biologics. Cumulative probabilities for use of biologics were 4.7%, 5.8%, and 8.6% at 12 months, 36 months, and 96 months, respectively, while the probabilities for surgery were 67.2%, 71.6%, and 77.7%, respectively. Five mortalities were recorded, including 2 cases of anal cancer, 2 CD-related complications, and one case of pneumonia. Over 40% of CD patients presented with perianal disease at diagnosis. Patients with PCD had poor outcome, with young age of onset, multiple antibiotic use, and repeated surgery.

Review article: pathogenesis of Crohn's perianal fistula-understanding factors impacting on success and failure of treatment strategies.

Evidence from groups who have studied fistula aetiology and extrapolation from interventional studies supports a multifactorial hypothesis of Crohn's perianal fistula, with several pathophysiological elements that may contribute to fistula formation, persistence and resistance to treatment. An evidence synthesis of current understanding of pathophysiological factors underlying Crohn's perianal fistula is presented, exploring the fundamental reasons why some treatments succeed and others fail, as a means of focussing clinical knowledge on improving treatment of Crohn's perianal fistula. Evidence to support this review was gathered via the Pubmed database. Studies discussing pathophysiological factors underpinning perianal fistula, particularly in Crohn's disease, were reviewed and cross-referenced for additional reports. Pathophysiological factors that impact on success or failure of interventions for Crohn's perianal fistulae include the high-pressure zone, obliterating the dead space, disconnecting the track from the anus, removing epithelialisation, eradicating sepsis and by-products of bacterial colonisation, correcting abnormalities in wound repair and removing the pro-inflammatory environment which allows fistula persistence. Most current interventions for Crohn's perianal fistulae tend to focus on a single, or at best two, aspects of the pathophysiology of Crohn's anal fistulae; as a result, failure to heal fully is common. For an intervention or combination of interventions to succeed, multiple factors must be addressed. We hypothesise that correct, timely and complete attention to all of these factors in a multimodal approach represents a new direction that may enable the creation of an effective treatment algorithm for Crohn's anal fistula.

Sa1724 - Expanded Allogeneic Adipose Derived Mesenchymal Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Crohn's Disease Has Rapid Onset of Clinical Remission and Low Relapse Rate by Week 52

Sa1724 - Expanded Allogeneic Adipose Derived Mesenchymal Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Crohn's Disease Has Rapid Onset of Clinical Remission and Low Relapse Rate by Week 52

Anal Fistulas in Severe Perineal Crohn's Disease: Mri Assessment in the Determination of Long-Term Healing Rates.

The European Crohn's and Colitis Organization recommends magnetic resonance imaging (MRI) of anal fistulas to decide on the drug/surgery strategy. No evidence is available on the long-term impact of MRI features on fistula healing. The aim of this study was to evaluate the benefit of combined drug/surgery strategies for the treatment of perianal Crohn's fistulas based on MRI factors at referral. The clinical event (anal abscess, new fistula tract, cellulitis), therapeutic intervention (introduction/optimization of immunosuppressant/biologics, anal surgery, intestinal resection, stoma), and MRI data were prospectively recorded for patients with Crohn's disease (CD) and anal fistulas. Healing was defined by fulfilment of all the following conditions: no discharge or pain, closure of the external opening of the fistula, no visible internal opening, no abscess, and no subsequent draining seton or drainage procedure performed during at least 1 year of follow-up. Seventy CD patients with anal fistulas and MRI evaluations were followed for 70 months. The cumulative rates of fistula healing were 25%, 40%, 50%, and 70% at 12, 24, 36, and 72 months, respectively. Severe, complex, branched, and high fistulas were associated with a less favorable outcome. Surgical closure of the tract improved the healing rates better than treatment with biologics or thiopurines. Male sex, A1 luminal phenotype, and anal ulceration at referral were independently associated with a higher healing rate. Therapeutic strategies for perianal fistulizing CD require robust anatomical and healing evaluations. Combined strategies using biologics to improve both drainage and secondary closure of the fistula tracts merit further study.

Stem Cell Therapy for Perianal Crohn's Disease.

To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.

P691 Cx601, a novel stem cell therapy for complex perianal fistulas in Crohn’s disease has rapid onset of clinical remission and low relapse rate by week 52

P691 Cx601, a novel stem cell therapy for complex perianal fistulas in Crohn’s disease has rapid onset of clinical remission and low relapse rate by week 52

P828 Frequency and characteristics of perianal fistulas in Crohn’s disease

P828 Frequency and characteristics of perianal fistulas in Crohn’s disease

Pathogenesis and persistence of cryptoglandular anal fistula: a systematic review.

Anal fistulas continue to be a problem for patients and surgeons alike despite scientific advances. While patient and anatomical characteristics are important to surgeons who are evaluating patients with anal fistulas, their development and persistence likely involves a multifaceted interaction of histological, microbiological, and molecular factors. Histological studies have shown that anal fistulas are variably epithelialized and are surrounded by dense collagen tissue with pockets of inflammatory cells. Yet, it remains unknown if or how histological differences impact fistula healing. The presence of a perianal abscess that contains gut flora commonly leads to the development of anal fistula. This implies a microbiological component, but bacteria are infrequently found in chronic fistulas. Recent work has shown an increased expression of proinflammatory cytokines and epithelial to mesenchymal cell transition in both cryptoglandular and Crohn's perianal fistulas. This suggests that molecular mechanisms may also play a role in both fistula development and persistence. The aim of this study was to examine the histological, microbiological, molecular, and host factors that contribute to the development and persistence of anal fistulas.

985 - CX601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells (EASC), for Complex Perianal Fistulas in Crohn's Disease: Long-Term Results from a Phase III Randomized Controlled Trial

985 - CX601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells (EASC), for Complex Perianal Fistulas in Crohn's Disease: Long-Term Results from a Phase III Randomized Controlled Trial

OP009 Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn's disease: 52-week results of a phase III randomised controlled trial

Background: Existing therapies for perianal fistulas in Crohn's disease (CD) are associated with a high failure rate and few have been evaluated in randomised controlled trials (RCTs) using hard endpoints. The 24-week results of a RCT showed that Cx601 added onto standard of care was safe and effective for treatment-refractory complex perianal fistulas with a significantly greater proportion of patients achieving clinical and radiological combined remission (CR) compared with placebo+standard of care. We aimed to determine whether this efficacy and safety was maintained over the long-term (52 weeks) (NCT01541579). Methods: Patients with inactive or mildly active luminal CD and treatment-refractory, draining, complex perianal fistulas were randomised (1:1) to Cx601 (single injection of 120 million eASC to all tracts+standard of care) or control (placebo+standard of care) in this phase III, double-blind, parallel-group multicentre study. An unblinded surgeon administered the treatment and a blinded gastroenterologist evaluated the therapeutic effect. Efficacy was evaluated in the mITT (randomised, treated and ≥1 post-baseline efficacy assessment) population at week 52. Pre-specified endpoints included CR (closure of all treated external openings [EOs] that were draining at baseline assessed clinically, and absence of collections >2 cm in the area of the treated perianal fistulas by blinded central MRI reading) and clinical remission (closure of all treated EOs). Sustained CR at week 52 was also evaluated. Results: 212 patients were randomised to Cx601 (n=107) or control (n=105); 61.8% completed the 52-week follow-up (Cx601, n=70; control=61). The beneficial effect observed at week 24 (CR in Cx601 51.5%, control 35.6%; p=0.021) was sustained at week 52; a significantly greater proportion of patients receiving Cx601 vs control achieved CR (56.3% vs 38.6%; p=0.010), and clinical remission (59.2% vs 41.6%; p=0.013) at week 52. Of patients with CR at week 24, a greater proportion of those treated with Cx601 vs control had no relapse at week 52 (75.0% vs 55.9%). Rates and types of treatment related adverse events were similar in both groups (20.4%, Cx601 vs 26.5%, control). Conclusions: The efficacy of Cx601 in treatment-refractory complex perianal fistulas of CD patients was sustained for up to 1 year after a single administration. The results also support the favourable tolerability of Cx601 over the long-term.

OP008 An innovative treatment for refractory perianal fistulas in Crohn's disease: local micro reinjection of autologous fat and adipose derived stromal vascular fraction

OP008 An innovative treatment for refractory perianal fistulas in Crohn's disease: local micro reinjection of autologous fat and adipose derived stromal vascular fraction

P672 Surgical and anti-TNFs combined therapy prevents Crohn's perianal fistula recurrence: a systematic review and meta-analysis

Background: The management of perianal Crohn's disease (CD) fistula represents a significant challenge. We aimed to conduct a meta-analysis to evaluating the efficacy and safety of combined surgical and anti-TNFs treatment compared with either single therapy in fistulising perianal CD. Methods: MEDLINE, EMBASE and the Cochrane database were searched. The primary outcome was the number of patients who developed fistula closure as defined by the primary studies. Results: Eight studies (3 prospective studies and 5 retrospective studies) invoving 688 patients were included. The rate of fistula closure of the combination therapy (78.5%, 197/251) was not significant higher compared with the surgical therapy alone (65.2%, 215/330) (OR 2.21, 95% CI 0.83–5.90, p=0.11). Similarly, neither the rate of complete closure nor the rate of partial closure was significantly different between the two groups. Significant lower proportion of patients in the combination group developed fistula recurrence (20.8%, 11/53) compared with the single surgical group (76.1%, 35/46) (OR 0.13, 95% CI 0.03–0.58; p=0.007). No significant difference observed between the combination therapy and anti-TNF therapy alone in the rate of fistula closure. However, the combination therapy was associated with a 76% risk reduction of fistula recurrence (OR 0.24, 95% CI 0.06–0.93, p=0.04, n=57). The adverse events were mostly related to anti-TNFs infusion. Conclusions: Combined surgical and anti-TNFs therapy did not significant improve the fistula closure than the surgery or anti-TNFs therapy alone. However, it is superior to either therapy in preventing fistula recurrence of fistulising perianal CD without causing more adverse events.

P398 An objective measure of response to treatment for patients with Crohn's perianal fistulas on anti-TNF treatment

Background: Magnetic Resonance Imaging (MRI) is the preferred test for assessing fistulising perianal Crohn's disease and its response to anti-TNF therapy. Currently, radiological assessment of perianal fistulas and whether it has responded to treatment is subjective and variable according to radiologist interpretation. This study investigates a complementary objective measurements to reduce inter and intra-observer variability. Methods: A cohort of patients with perianal Crohn's fistulas treated at a tertiary centre with anti-TNF therapy was identified, and for whom pelvic MRI was available at baseline and follow-up. Two gastrointestinal radiologists measured fistula volumes, mean signal intensity and time taken to measure fistula volumes on baseline and follow-up MRI scans using a validated open-source segmentation software programme. One gastrointestinal radiologist repeated the measurements after 2 months. Three different gastrointestinal radiologists also assessed fistula response to treatment (improved/worse/unchanged) by comparing the MRI scans for each patient. Agreement between these radiologists was assessed using the kappa statistic. Intra-class correlation coefficient (ICC) was used to compare agreement between radiologists and to assess intra-observer variability for one radiologist. Results: Eighteen patients were recruited of which 6 (33%) were female and median age was 29 years old (range 19–52). Inter-observer variability was very good for volume and mean signal intensity with ICC of 0.95 (95% CI 0.91–0.98) and 0.95 (95% CI 0.90- 0.97) respectively. Intra-observer variability for one radiologist was also very good for volume and mean signal intensity with ICC of 0.99 (95% CI 0.97–0.99) and 0.98 (95% CI 0.95- 0.99) respectively. Average time taken to calculate volume measurements was 202 and 250 seconds for readers 1 and 2. Subjective assessment of response between the 3 radiologists was good; kappa of 0.69 (95% CI, 0.49–0.90). All 3 radiologists agreed in 72% of patients. A significant association was found between percentage volume change and subjective consensus agreement of response made by the radiologists (p=0.001). Median volume change for improved, stable or worsening fistula response was -67% (IQR −78, −47), 0% (IQR −16, +17), and +487% (IQR +217, +559) respectively. Conclusions: Objective measurements of fistula volume and signal intensity on MRI scans can be made rapidly using segmentation software with good agreement between radiologists. Percentage changes in measured volume are significantly correlated with judgements of response made by radiologists and could potentially be used to decrease variability in fistula assessment. These measurements can potentially be used to track fistula response over time.

P681 Assessing internet based information used to aid patient decision making in surgery for perianal Crohn's fistula

P681 Assessing internet based information used to aid patient decision making in surgery for perianal Crohn's fistula