Relapse Of Colitis Research Articles

P552 Withdrawal of immunomodulator medications (IM) in children with inflammatory bowel disease on combination therapy of IM and biologics

Abstract Background Anti-tumor necrosis factor (anti-TNF) antagonists such as infliximab (IFX) are widely used for the treatment of inflammatory bowel disease (IBD). Early studies suggested that combination therapy with IFX and an immunomodulator drug (IM) such as azathioprine (AZA) or methotrexate (MTX) may help in optimising biologic pharmacokinetics, minimising immunogenicity, and improving outcomes. On the other hand, IM especially AZA, may increase infection and cancer risks with no clear evidence on long-term benefits of combination therapy. As such, stopping IM and continuation of an anti-TNF agent as a monotherapy in patients in remission seem to be a sensible strategy. However, there is no evidence to prove the efficacy of this strategy. The aim of this work was to examine frequency and factors associated with the first relapse after IM withdrawal in a cohort of children with IBD on combination therapy. Methods In a retrospective multicenter pediatric study, we determined the percentage of patients and investigated potential factors associated with the first relapse in a cohort of children and young adults with IBD on combination therapy of anti-TNF and IM after stopping IM. Cox regression analysis was used to assess factors associated with IBD relapse following IM withdrawal. Results A total of 79 patients (42, males, 62 Crohn’s disease) with 74 (93.7%) on IFX were included. In addition to the anti-TNF agent, 33 (41.8%) were on AZA and the rest were on MTX. The median duration of combination therapy was 2.0 (IQR 1.2–2.8) years. All participants were in clinical remission at the time of IM withdrawal. The median duration of follow-up after IM withdrawal was 11.0 (IQR 5.0–16.2) months. Only 8 (10.1%) patients relapsed over that period of follow-up. Age, sex, disease phenotype at diagnosis, family history of IBD, type of IM, and biochemical markers and clinical disease activity indices prior to IM stoppage did not predict a future relapse. Among those with CD on IFX who maintained remission, the median last IFX trough level before IM withdrawal was 6.25 Ug/ml (IQR: 4.04–8.70) vs. 3.8 Ug/ml (IQR: 2.40–11.6) in those who relapsed (p = 0.4). Conclusion Over short-term follow-up, the majority of children on combination therapy of IM and an anti-TNF agent remain in clinical remission after IM withdrawal.

P138 Basal plasma cells in normal large bowel: what is normal?

Abstract Background Basal plasma cells (BPC) are a diagnostic criterion for inflammatory bowel disease (IBD) and their persistence following therapy also indicates an increased risk of relapse. However neither the definition of basal plasma cells nor what is normal has been well established. We examined these parameters and determined whether there is reginal variability throughout the large bowel. Methods We looked at two patient populations. Group A) Biopsies from 6 standardised sites around the colon (cecum to rectum) from 37 patients who had normal colonoscopy at IRCCS Sacro Cuore Hospital, Negrar, Verona, Italy for symptoms suggesting irritable bowel syndrome, who were free of all medical therapy. Group B) a validation cohort from Mt Sinai Hospital Toronto using sections from the same 6 sites from 16 subtotal and total colectomy specimens performed for non-obstructing colonic carcinoma, primarily Lynch syndrome. Basal plasma cells were counted between two crypts in both the basal 5%, and the basal 20% of the mucosa. A partitioned visual analogue scale (PVAS) was also developed to see if this could replace counting, especially as the distance between crypts in IBD is variable Results In group A, in the lowest 5% part of the lamina propria, basal plasma cells were found throughout the large bowel and were highest in the proximal colon and lowest in the rectosigmoid. The maximum number of plasma cells between crypts was seven for the cecum and two for the rectum, with a gentle gradation between these two. The PVAS (range 1–5) varied from a maximum of 2 proximally to 1 distally. When the basal 20% was counted, the scores ranged from 35 in the cecum to 12 in the rectum, again with a gradation between, but the PVAS increased from a maximum of 3 proximally to 2 in the rectum. In group B the results were virtually to Group A and the PVAS scores were also virtually identical, The main difference was that at least one plasma cell was seen in all sections, likely because tissue sections encompass a much larger area. These results were all statistically significant. Conclusion The normal large bowel has a gradation of plasma cells that is highest proximally and lowest distally, however assessed, and needs to be taken into account when assessing the presence of basal plasma cells as an indicator of increased likelihood of relapse of IBD. The PVAS developed can replace the chore of counting, and is likely more meaningful when architectural distortion is present.

P705 Dietary practices and beliefs of patients with older-onset inflammatory bowel disease: A prospective UK study

Abstract Background In an aging population, 25–35% of those with inflammatory bowel disease (IBD) are over 60 years old. A third of these are diagnosed at or over the age of 60 (older-onset IBD). Virtually no studies exist exploring the dietary practices and beliefs of patients with older-onset IBD. Elderly patients with IBD are at increased risk of nutritional deficiency and associated complications making it all the more important to understand the dietary habits and self-imposed restrictions of this group. Methods A prospective, cross-sectional, questionnaire-based study is being conducted across NHS Trusts within the UK. Two-hundred patients with older-onset IBD will be recruited to complete a questionnaire regarding demographics and dietary practices. Here we provide an interim analysis of the data collected from the first 75 patients. Results Mean patient age is 73 years, 51% are male and 95% Caucasian. 68% have ulcerative colitis. Mean disease duration is 6 years. Thirty-six per cent of patients believe diet was an initiating factor in their IBD and this is based on their own experience (78%) or advice from a gastroenterologist (33%), dietitian (22%) or GP (22%). Fifty-six per cent of patients report a disease relapse in the last year and just under a third believe that diet could trigger a relapse. The most commonly identified triggers are spicy foods (61%), raw fruit and vegetables (57%), fatty foods (39%) and milk products (30%). Sixty-three per cent of patients avoid certain foods to prevent a relapse of IBD. The most commonly avoided foods are spicy (81%) and fatty foods (66%), carbonated drinks (60%), red meat (53%), raw fruit and vegetables (49%) and alcohol (49%). Half of patients report being able to find specific advice regarding dietary recommendations in IBD and 72% of these obtain this information from the internet. A quarter of patients avoid eating the same menu as their family at least some of the time to prevent relapse of their IBD and 36% of patients avoid eating out. One in five patients has tried a specific exclusionary diet to help manage their symptoms, most commonly a gluten free diet, in the absence of coeliac disease, in 12% of patients. Conclusion Despite a relatively low proportion of older-onset IBD patients believing diet is implicated in the initiation of their disease or its relapse, a significant number continue to restrict their diet. This, along with co-existing frailty, comorbidities and polypharmacy, may put this group of patients at increased risk of nutritional deficiency and its associated complications as well as impacting upon quality of life. Improved knowledge of the dietary habits of those with ‘older-onset’ IBD will allow healthcare professionals to identify those at risk and offer appropriate dietary interventions.

P612 Dietary practices and beliefs of British South Asians with inflammatory bowel disease: A prospective UK study

Abstract Background The increasing incidence of inflammatory bowel disease (IBD) in newly industrialised countries and immigrant populations appears to outpace that which genetic influences alone could instigate. Environmental factors, in particular, the western diet, are therefore implicated in its aetiopathogenesis. Limited data exist on the dietary practices of the migrant South Asian population with IBD. We aim to describe the dietary practices of British South Asian IBD patients and information resources utilised to guide these beliefs. Methods A prospective, cross-sectional, questionnaire-based study is being conducted across hospitals in the UK. Two-hundred South Asian patients with IBD are being recruited to complete a questionnaire regarding demographics and dietary practices. Results Data from 118 patients are available to date. Mean patient age is 43 years (51% female). Sixty-five per cent have ulcerative colitis (UC) and 33% Crohn’s disease (CD). Fifty-one per cent are of Indian ethnicity, 37% Pakistani and 10% Bangladeshi. Forty-nine per cent of patients were born in the UK to parents who were born outside of the UK and 51% of patients were born outside the UK. Mean disease duration is 10.5 years. Forty-six per cent considered diet to be an initiating factor in their IBD, based on their own experience (85%) as well as information from internet resources (31%) and other patients with IBD (19%). Fifty-nine per cent of patients felt that diet had triggered a relapse of their disease. Most commonly reported foods were spicy (69%) and fatty foods (47%), milk products (44%) and red meat (37%). Eighty-six per cent of patients avoided certain foods in an attempt to prevent an IBD ‘flare’. Most frequently avoided foods were spicy foods (76%), fatty foods (69%), red meat (60%), coffee (55%), carbonated drinks (54%) and milk products (53%). One in four patients had tried a specific exclusionary diet, with 13% having tried a gluten-free diet in the absence of coeliac disease, to manage their symptoms. Just over a half of patients reported being able to find specific dietary advice for IBD, most commonly via the internet. Over half of patients avoided eating the same meal as their family or eating out to prevent relapse of their IBD. 1 in 3 consumed certain foodstuffs or nutritional supplements to prevent a relapse of IBD, most commonly turmeric in 25% of these patients. Conclusion Dietary restriction may be highly prevalent amongst the British South Asian IBD community with a high proportion reporting diet as an initiating factor and trigger for disease flares. Studies on immigrant populations may hold valuable clues regarding the influence of migration, environmental influences and drift from traditional cultural practices on IBD aetiopathogenesis and related symptoms. A larger dataset will be presented at conference proceedings.

Use of Vitamin D With Anti-Tumor Necrosis Factor Therapy for Crohn's Disease.

BackgroundVitamin D (VD) has an important role in regulating gut mucosal immunity, and seems to be inversely linked to disease activity and more frequent relapses in inflammatory bowel disease. In this study, we evaluated patients with Crohn’s disease (CD) treated with anti-tumor necrosis factor (TNF) in association with VD.MethodsA double-blind, randomized, prospective study was conducted. Thirty patients with a history of moderate to severe CD, in use of anti-TNF, of both sexes, 18 to 70 years, with the dosage of VD < 75 nmol/L (30 ng/mL) were randomized and divided into three groups: group 1 (G1): 10 patients received 2,000 IU VD, per os (PO)/week for 8 weeks; group 2 (G2): 10 patients received 10,000 IU VD, PO/week for 8 weeks; group 3 (G3): 10 patients received 50,000 IU VD, PO/week for 8 weeks. Before and at the end of 8 weeks patients were submitted to VD, fecal calprotectin (FC) and C-reactive protein (CRP) dosage. Follow-up period was 52 weeks, and they are checked for disease activity recurrence (Crohn’s disease activity index (CDAI) > 150, FC > 300 and computerized tomography (CT) scan), FC, CRP, and VD levels.ResultsIncreased VD levels were observed in all groups (P < 0.0001). CRP did not change. There was a significant decrease of FC in G3 (1,014 ± 850 vs. 483 ± 564; P = 0.04), no significant decrease in G2 (76,767 ± 751 vs. 535 ± 823; P = 0.2) and increase in G1 (1,101 ± 744 vs. 1,357 ± 819; P = 0.4). During the 52-week follow-up period, it was showed that recurrent disease activity (CDAI > 150, FC > 200 and CT scan) was predominant in patients with VD < 30 group, and the remission rate was predominant in patients with VD > 30 group (P = 0.0001). A statistically significant difference in VD levels was noted in CD patients after 52 weeks that presented flare or disease remission (P = 0.001).ConclusionsUse of VD associated with anti-TNF treatment may improve clinical response in CD. VD levels greater than 30 ng/mL have better rates of remission.

Postoperative Pain Management in Patients With Ulcerative Colitis.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease. Pain management can be challenging in patients with IBD because there are limitations on the use of analgesics. Use of nonsteroidal anti-inflammatory drugs is not recommended in patients with IBD because there is risk of relapse of IBD and an overall increase in disease activity. Opioids, although frequently used for treating severe acute pain, can have additional risks and complications in patients with IBD such as ileus, toxic megacolon, and narcotic bowel syndrome. Furthermore, little information is available in the literature on pain management in these patients undergoing noncolorectal surgery. This report describes 2 patients with UC in whom postoperative pain following oral and maxillofacial surgery was managed by intravenous patient-controlled analgesia with pentazocine. Apart from the development of acute dystonia in 1 case that was likely due to the use of droperidol for prevention of postoperative nausea and vomiting, postoperative pain was well controlled by pentazocine in both patients without any complications or UC exacerbations.

Chronic Unpredictable Mild Stress in Rats Induces Colonic Inflammation.

Chronic psychological stress is associated with an increased risk for relapse of inflammatory bowel diseases (IBD) and impedes the treatment of this condition. However, the impact of stress on the risk of IBD onset remains unclear. The goal of the present study was to examine whether chronic unpredictable mild stress (CUMS) could initiate or aggravate the onset of colon inflammation in rats which, in turn, would be capable of triggering bowel disease. We found that CUMS exposure increased infiltration of CD-45 positive cells and MPO activity, as well as augmented the expression of the inflammatory cytokines, IFN-γ and IL-6 within the colon of these rats. In addition, CUMS treatment changed the composition and diversity of gut microbiota and enhanced intestinal epithelial permeability, indicating the presence of a defect in the intestinal barrier. This CUMS-induced disruption of mucosal barrier integrity was associated with a reduction in expression of the tight junction protein, occludin 1, and an inhibition in mucosal layer functioning via reductions in goblet cells. Results from bacterial cultures revealed an increased presence of bacterial invasion after CUMS treatment as compared with that observed in controls. Thus, our data indicate that CUMS treatment induces alterations of the fecal microbiome and intestinal barrier defects, which facilitates bacterial invasion into colonic mucosa and further exacerbates inflammatory reactions within the colon. Accordingly, chronic stress may predispose patients to gastrointestinal infection and increase the risk of inflammation-related gut diseases.

Effect of the Sphingosine Kinase 1 Selective Inhibitor, PF543 on Dextran Sodium Sulfate-Induced Colitis in Mice.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, which often affects colon or rectum or both. It is now well recognized that sphingosine kinases-1/sphingosine-1-phosphate (S1P) signaling may have a very significant potential as targets for therapeutic intervention in UC. Compared with the pure dextran sodium sulfate group, administration of PF543 significantly reduced clinical symptoms with less weight loss, diarrhea, and shortening of the colon. The severity of colitis was improved with reduced disease activity index and degree of histological damage in colon. Moreover, treatment with PF543 not only decreased S1P but also inhibited mRNA expression of proinflammatory factors such as interleukin (IL)-1β and IL-6. This suggests that PF543 might exhibit an anti-inflammatory function against colitis through inhibition of expression of proinflammatory factors.

Increased Risk of Hepatocellular Carcinoma in Patient with Inflammatory Bowel Disease and Hemochromatosis: A Case Report

Inflammatory bowel diseases could be associated with extra-intestinal manifestation; in this report we describe the case of a patient with ulcerative colitis who was diagnosed with genetic hemochromatosis (homozygosity for C282Y in the HFE gene) after a colitis relapse with high levels of serum ferritin (2000 ng/mL). After the genetic diagnosis patient underwent to an upper abdomen US with CEUS, with evidence of a 2 cm nodule in VIIs, suggestive for hepatocellular carcinoma, then confirmed with MR and CT scan. Patient underwent surgical resection of the lesion with histological confirmation of the malignant neoplasia. A correlation between the two diseases is not clear, but inflammatory bowel diseases and genetic hemochromatosis have some similarity: both diseases are related with functional reduction of hepcidin and in both diseases the mutations are located in chromosome 6p. Furthermore, regarding therapies, there is no evidence that iron chelation therapies could aggravate symptoms of ulcerative colitis, instead a chronic therapy with mesalazine could induce a chronic liver damage, worsening the hemochromatosis related liver damage.

Hormone Therapy for Cancer Is a Risk Factor for Relapse of Inflammatory Bowel Diseases

Background & Aims:Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBD). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD.Methods:We conducted a retrospective cohort study, collecting data from 5 medical centers on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission.Results:Our analysis included 447 patients with IBD (44% with Crohn’s disease, 53% with ulcerative colitis, and 3% with IBD-unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse following a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18–2.71; HR for immunomodulators, 2.22; 95% CI, 1.38–3.55; HR for biologics, 1.95; 95% CI, 1.01–5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21–3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01–3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank=0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission.Conclusions:In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

Relationship of Demographic and Clinical Variables with the Severity of Disease in Patients with Ulcerative Colitis Relapse in Qom Shahid Beheshti Hospital During 2017, (Iran)

Relationship of Demographic and Clinical Variables with the Severity of Disease in Patients with Ulcerative Colitis Relapse in Qom Shahid Beheshti Hospital During 2017, (Iran)

Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn’s disease: a pilot study

Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission. In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months). At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts≥i2). The Rutgeerts score was significantly correlated with the Watson score (ρ= 0 .73; P< .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P= .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P= .036). CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.

Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations.

A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy. Although a lesser number of meta-analyses have been performed on the use of FCAL as a surrogate marker of disease activity, a close correlation between FCAL and endoscopic activity of IBD has been shown. With respect to the predictive capacity of FCAL for IBD relapse, a single meta-analysis published indicates that this role is more limited. Furthermore, FCAL thresholds vary considerably depending on the clinical setting and, what is more concerning, among different commercially available assays due to a lack of FCAL concentration interchangeability. Here, we summarise recent publications about the role and limitations of FCAL in IBD, with a special focus on meta-analyses, and give an overview of alternative faecal biomarkers.

The triggering role of Clostridioides difficile infection in relapsed IBD outpatients

Although the exact aetiology of inflammatory bowel disease (IBD) is unknown, one hypothesis suggests that the inflammation may be the consequence of an altered or pathogenic microbiota in a genetically susceptible host. The aim of this study was to assess the frequency of enteral infections in patients with relapse of IBD, and to evaluate the clinical utility of faecal calprotectin (FC) and faecal matrixmetalloproteinase- 9 (MMP-9) in the differential diagnosis of relapses with different origins, and to determine the recurrence rate of Clostridioides difficile (C. difficile), the hospitalisation and colectomy rate among C. difficile positive IBD patients at the end of 4 years follow-up period. Methods: In this prospective, “real life” study clinical data, serum and stool samples were assessed. Results: Overall, 135 outpatients with IBD were enrolled [91 IBD patients who relapsed and 44 subjects in clinical remission (control group)]. C. difficile A/B toxins were detected in 42.2% of all cases. Candida was presented in 9.9% among the enrolled subjects. We found significant difference between FC and MMP-9 values in patients in relapse and remission, but not in C. difficile positive and negative cases. Our results revealed an association between previous antibiotic use and the rate of toxigenic C. difficile. Toxigenic C. difficile positivity recurrence rate was 4.4%. Hospitalisation during follow-up due to IBD was 45.4% and 35% in C. difficile positive and negative group, respectively. Value of FC and MMP-9 did not predict the need of hospitalisation. Conclusions: The occurrences of toxigenic C. difficile and Candida positivity were excessively high in our patients in an acute relapse, which suggests the importance of intestinal microbiota in IBD. FC and MMP-9 has no diagnostic value to differentiate between infection-induced and natural relapse. In our study was confirmed that hospitalisation rate was higher in C. difficile positive cases, but we did not find any relationship on long-term period.

Long-term clinical outcome after infliximab discontinuation in patients with inflammatory bowel disease

Objectives: We investigated the long-term clinical outcome and risk factors for clinical relapse in inflammatory bowel disease (IBD) patients after stopping infliximab (IFX).Materials and methods: We retrospectively reviewed the medical records of IBD patients who were treated with IFX in four university hospitals in South Korea. Among them, patients who discontinued scheduled IFX therapy with a favorable disease course were enrolled. Clinical relapse was defined as an increase in disease activity, addition of new drugs, or abdominal surgery.Results: In total, 28 ulcerative colitis (UC) patients and 17 Crohn’s disease (CD) patients were enrolled. The median duration of follow-up after discontinuation was 41 months (range: 8–109 months) in UC patients and 141 months (range: 66–262 months) in CD patients. The cumulative probability of relapse at 12 months was 32.1% in UC patients and 30.7% in CD patients. Fewer IFX infusions and a shorter duration of mesalamine treatment after IFX discontinuation were risk factors for relapse after IFX discontinuation in UC patients (p = .04 and .01, respectively). In CD patients, a higher erythrocyte sedimentation rate and CRP at IFX discontinuation and a shorter duration of azathioprine treatment after IFX discontinuation were risk factors for relapse (p = .03, .03 and .01, respectively).Conclusions: Approximately 30% of IBD patients who responded to IFX therapy experienced relapse within 1 year after discontinuation. We identified several risk factors for relapse. Further studies should identify factors predictive of the disease course after discontinuing IFX maintenance therapy.

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease

Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

Real-time Endoscopy-Guided Measurement of Rectal Mucosal Admittance Is a Novel and Safe Method for Predicting Ulcerative Colitis Relapse.

There are known associations between inflammatory bowel disease (IBD) and changes in mucosal paracellular permeability. We recently developed a novel catheter that can measure mucosal admittance (MA). Patients with ulcerative colitis (UC) in clinical remission underwent real-time MA measurement during colonoscopy between June 2014 and July 2015 and were prospectively followed. MA measures were taken from normal-appearing mucosa using the Tissue Conductance Meter (TCM). We examined relationships between mucosal admittance, clinical parameters at the time of MA measurement, and disease relapse during the follow-up period using the Cox proportional hazards model. We measured baseline MA in 54 patients with UC during remission, with no complications. Of these, 23 patients relapsed during the subsequent follow-up period, at a median of 25.8 ± 7.6 months. Rectal MA was the only predictor of disease relapse in multivariate analysis (P = 0.027). The optimal rectal MA cutoff value for relapse was 781.0 (area under the receiver operating characteristic curve, 0.712), and in patients who showed lower than normal cutoff values, there was a significantly higher likelihood of relapse compared with other patients (log-rank test, P < 0.001). High rectal MA measured by TCM is associated with long-term sustained remission. Real-time rectal MA measurement using a novel endoscopy-guided catheter could be a safe and useful means of predicting prognosis for patients with UC in remission.

2523 Noninvasive biomarkers for inflammatory bowel disease: Drawbacks and potential

OBJECTIVES/SPECIFIC AIMS: Approximately 1.6 million Americans suffer from inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn’s disease. It is a challenge for both physicians and patients alike to manage the disease, primarily due to lack of disease specific biomarkers. Endoscopy remains the gold standard to diagnose and evaluate IBD activity. Current biomarkers or their combinations cannot adequately predict IBD progression or relapse, and response to therapy. METHODS/STUDY POPULATION: In total, 97 IBD patients recruited at University of Kentucky undergoing endoscopy. Patients medical information was collected from electronic database including C-reactive protein (CRP), fecal calprotectin (FC), endoscopy/pathology report. RESULTS/ANTICIPATED RESULTS: The mean CRP and FC levels were 1.3 (normal &lt;1) and 679 (normal &lt;162), respectively. FC (sensitivity 74%) was more reliable to predict mucosal inflammation compare to CRP (sensitivity 36%). However, 52% of patients did not have FC performed (vs. CRP only 4%), and 45% of these patients failed to submit stool sample for analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests FC is the most promising noninvasive marker for disease monitoring in IBD. It correlates well with endoscopic activity and mucosal inflammation. However, further analysis must be done to evaluate barriers to testing and issues with compliance from patients. We feel strongly that a blood biomarker for disease activity is vital for disease monitoring and response to therapy in IBD.

A characterization of pro-inflammatory cytokines in dextran sulfate sodium-induced chronic relapsing colitis mice model

Repeated cycles of dextran sulfate sodium (DSS) administration in mice, inducing chronic relapsing colitis, have been used to mimic human ulcerative colitis (UC). However, no systematic characterization of pro-inflammatory cytokines in these DSS mice has been reported. In this study, the development of colitis was examined by assessment of the disease severity and inflammation in the colon of C57BL/6 mice that received DSS. ELISA was used to analyze the levels of pro-inflammatory cytokines in serum, colon, spleen and supernatant of cultured splenocytes. mRNA levels of the above cytokines in colon and mesenteric lymph node (MLN) were measured with RT-PCR. The mice receiving three cycles of 2% DSS over a 43-day period showed a fluctuating appearance of diarrhea and bloody feces, and a significant reduction in body weight and colon length. When compared with normal control mice, an increase in TNF-α level in serum was detected in the DSS mice, along with a decrease in the amounts of TNF-α, IL-17, IL-1β and IL-6 in the colonic tissue. However, mRNA levels of these cytokines were found to be significantly increased in the colon while decreased in the MLN of the colitis mice. Further, the ELISA assay suggested a pronounced increase of TNF-α production by cultured splenocytes with PMA/ionomycin re-stimulation but no increase in its presence in spleen tissue upon DSS challenge. In conclusion, we have systematically demonstrated the dysregulation of pro-inflammatory cytokines in the DSS-induced chronic relapsing colitis model, which will provide markers to test emerging therapeutic strategies by this model.