IBD Flare Research Articles

Environmental triggers in IBD: a review of progress and evidence.

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

Increased risk of acute arterial events in young patients and severely active IBD: a nationwide French cohort study

ObjectiveMagnitude and independent drivers of the risk of acute arterial events in IBD are still unclear. We addressed this question in patients with IBD compared with the general population at...

98 - What is a Flare of IBD?: The Manitoba Living with IBD Study

98 - What is a Flare of IBD?: The Manitoba Living with IBD Study

Sa1869 - What are the Most Common Symptoms Reported in a Self-Reported Flare of IBD? the Manitoba Living with IBD Study

Sa1869 - What are the Most Common Symptoms Reported in a Self-Reported Flare of IBD? the Manitoba Living with IBD Study

P548 Hepatitis B virus reactivation in hepatitis B virus infected patients with inflammatory bowel disease receiving anti-tumor necrosis factor-alpha therapy

Background: Reactivation of hepatitis B virus (HBV) is one of the most important side effects in IBD patients with HBV infection treated with anti-TNF-alpha agents. We investigated the rate of prophylaxis and the risk of HBV reactivation in HBV infected patients with IBD receiving anti-TNF-alpha therapy. Methods: This was a retrospective multicenter study including 14 academic teaching hospitals in Korea. IBD patients with HBV infection (HBsAg-positive) who treated with anti-TNF-alpha agents were enrolled. Medical records of patients were reviewed and data were collected using web-based case report form. Results: A total of 61 patients (18 UC, 43 CD) were included. 70% were male and mean age at diagnosis was 34.9±12.0 years. Indications for anti-TNF-alpha therapy were steroid-dependency, refractoriness to conventional therapies, or fistulizing disease. Among 43 patients who tested serum HBV-DNA levels, 35 (81%) were positive for HBV-DNA prior to anti-TNF-alpha therapy. Only half of the patients (51%) received prophylactic anti-viral agents. During the follow-up of median 24 months, 16.4% of patients experienced HBV reactivation, of which 6 patients (60%) were taking concomitant azathioprine. Median duration of anti-TNF-alpha therapy before HBV reactivation was 9 months. HBV reactivation was managed by change or adding of anti-viral agents in 6 patients, discontinuing ant-TNF-alpha in 1 patient, and combination of both in 2 patients, achieving virological response in most patients (90%). HBV reactivation was more frequent in non-prophylaxis group than prophylaxis group (10% vs 24.1%, p=0.15). No other predictors for HBV reactivation were identified. There was no difference in the rates of IBD flare, IBD-related surgery or hospitalization between two groups. Conclusions: HBV reactivation was not infrequent in HBsAg-positive IBD patients treated with anti-TNF-alpha agents. Prophylaxis for HBV reactivation and careful monitoring should be performed for such patients.

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate pro-inflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.

OC-039 Improving the Quality of Care and Reducing Costs of IBD Patients on Biologic Therapy Through a Multi-Disciplinary Biologics Clinic

Introduction NICE IBD quality standard (QS81) and the IBD Standards aim to deliver high quality and safe clinical care to IBD patients throughout the UK that is patient-centred and evidence based. These aims are supported by the national biologic therapy audit. To improve and standardise the care of our IBD patients on biologic therapy we began a weekly multi-disciplinary (physicians, IBD nurses, and pharmacist) virtual biologics clinic (VBC). Here, the response to therapy is monitored (clinical scoring, well-being, laboratory results), the scheduling of investigations are coordinated, and the review and writing of prescriptions undertaken. Methods We prospectively collected data from our VBC for 8 consecutive weeks. Changes to therapy on clinical grounds were noted, and the financial implications of these changes calculated. Calculations for IFX savings were based on an average dose of 300 mg per patient plus infusion costs. The ordering of required investigations and the occurrence of adverse clinical events were recorded. Results In 8 weeks, 360 patient reviews were performed relating to 327 patients (IFX = 207, ADA = 79, VEDO = 41). Therapy was adjusted in 41/327 patients (12.5%). 5 stopped biologic therapy, 19 switched drug, 10 reduced and 7 increased therapy frequency. Net saving in prescribing was £10,928 at 8 weeks (>£65 K/annum). The coordinated prescribing of medication and pharmacy sign off improved the delivery of therapy and patient satisfaction. 23 colonoscopies, 9 MR scans, and 45 outpatient appointments to assess response to therapy at 3 or 12 months, were scheduled from the VBC. 5 complications were highlighted (recurrent infection; 2 required surgery; cancer; severe IBD flare requiring hospitalisation). In total 118/357 (36%) patients had their care altered by VBC intervention (41 adjusted therapies, 77 scheduled monitoring and further clinical input. Conclusion The VBC provides a safe platform to initiate and monitor biologic therapies and to audit practices. The introduction of a multi-disciplinary VBC has altered the management of 118/327 patients (36%) based on clinical findings, results, and NICE guidance. Significant financial savings (£65 K per annum), the streamlining of prescribing, and superior patient monitoring have helped to improve the quality and safety of care provided. The transition to biosimilar anti-TNF therapies can also be facilitated using a VBC forum. Disclosure of Interest None Declared

PTH-060 Better Care for IBD Biologic Patients: The Impact of A Multi-Disciplinary Virtual Clinic

Introduction The IBD Standards, the Royal College of Physicians national biologic audit, and the NICE IBD quality standard (QS81) all aim to help deliver high quality, safe and appropriate clinical care to IBD patients throughout the UK. In line with these recommendations, and to improve and standardise the care of our IBD patients on biologic therapies we began a weekly multi-disciplinary (physicians, IBD nurses, and pharmacist) virtual biologics clinic (VBC). Here, the response to therapy is monitored (clinical scoring, well-being, laboratory results), the scheduling of investigations are coordinated, and the review and writing of prescriptions undertaken. Methods We prospectively collected data from our VBC for 8 consecutive weeks. Changes to therapy on clinical grounds were noted, and the financial implications of these changes calculated. Calculations for IFX savings were based on an average dose of 300 mg per patient, plus infusion costs. The ordering of required investigations and the occurrence of adverse clinical events were recorded Results In 8 weeks, 360 patient reviews were performed relating to 327 patients (IFX = 207, ADA = 79, VEDO = 41). Therapy was adjusted in 41/327 patients (12.5%). 5 stopped biologic therapy, 19 switched drug, 10 reduced and 7 increased the frequency of therapy. Net saving was £10,928 at week 8 (>£65 K/annum). The coordinated prescribing of medication and pharmacy sign off improved the delivery of therapy and patient satisfaction. 23 colonoscopies, 9 MR scans, and 45 outpatient appointments to assess response to therapy at 3 or 12 months and clinical input were scheduled from the VBC. The ordering of anti-TNF drug and antibody levels solely through the VBC reduced any duplication of requests and ensured the review and actioning of results. 5 complications were highlighted (recurrent infections; 2 requiring surgery; cancer; severe IBD flare requiring hospitalisation). Conclusion The introduction of a multi-disciplinary VBC has altered the management of 41/327 patients (12.5%) based on clinical findings and the results of investigations. Significant financial savings (£65 K per annum), the streamlining of prescribing, and superior patient monitoring have helped to improve the quality and safety of care provided. With better monitoring, care, NICE compliance, and financial prudence, this will help to sustain or service and practices. Disclosure of Interest None Declared

Ischemic Colitis Affects Descending Colon More and Cecum Less Often in Females Compared to Males

Introduction: Ischemic colitis (IC) has been increasingly diagnosed with advancement in medicine. However, gender differences have not been studied previously in IC. The aim of this study was to investigate the characteristics of IC in female compared to male patients. Methods: We reviewed medical records of patients with IC from January 2007 to January 2013 in two hospitals after IRB approval. Demographic details, clinical & lab data, imaging, endoscopy & histology, comorbidities, concomitant medications, surgery, length of hospital stay & death within 30 days of admission, were collected. The patients were divided into two groups: female IC group and male IC group. The diagnosis of IC was made based on clinical features consistent with IC with negative stool studies for infections & at least one diagnostic study consistent with IC (CT scan, colonoscopy, or histology). Exclusion criteria: age < 18, pregnancy, positive studies for gut pathogens, colonic ischemia due to trauma or mechanical causes, chronic bowel ischemia, acute flare of IBD & evidence of diverticulitis. Results: A total of 118 patients with IC were identified (mean age 69.4±15.07 years, 83.1% female). The clinical presentation, laboratory features, radiological findings, comorbidities, and use of 12 categories of commonly used medications were not different between both groups (p >0.05 for all variables). While the descending colon was affected more often in the female IC group (71.7% vs. 40%, p=0.007), the cecum was affected more often in the male IC group (8.1% vs. 25%, p=0.039). Colonoscopy was performed in 75.4% of patients; the findings of erosions or ulcerations in the affected colonic areas were more often seen in females compared to males (59.2% vs. 29.4%, p=0.027). Although, numerically, IC in males was worse in terms of the need for surgical interventions, ICU admission, mechanical ventilation, length of hospital stay, and death within 30 days, no statistically significant difference was observed (p >0.05 for all variables). Conclusion: The descending colon was affected more often in females, whereas the cecum was affected more often in males with IC. Erosions and ulcerations were seen more often in females. The outcomes of IC in males tend to be worse than females but were not significantly different. Larger studies are needed to further elucidate the gender differences in IC.

Current Status of the Treatment of Fulminant Colitis

Fulminant colitis is not a well-defined entity that constitutes a severe complication. It usually occurs in the course of ulcerative colitis and Clostridium difficile colitis. A multidisciplinary management combining a gastroenterologist and surgeons is crucial with intensive medical treatment and early surgery in non-responders. It is important to distinguish if we are facing a flare of IBD or, on the contrary, it is an infectious colitis, due to the fact that although general therapeutic measures to adopt will be the same, they will demand opposed specific measures.

Estado actual del tratamiento de la colitis fulminante

Fulminant colitis is not a well-defined entity, that constitutes a severe complication. It usually occurs in the course of úlcerative colitis and Clostridium difficile colitis. A multidisciplinary management combining gastroenterologist and surgeons is crucial with intensive medical treatment and early surgery in non-responders. It is important to distinguish if we are facing a flare of IBD or, on the contrary, it is an infectious colitis, due to the fact that although general therapeutic measures to adopt will be the same, they will demand opposed specific measures.

Evaluating toxicity from definitive radiation therapy for prostate cancer in men with inflammatory bowel disease: Patient selection and dosimetric parameters with modern treatment techniques

PurposeInflammatory bowel disease (IBD) is considered a contraindication to abdominopelvic radiation therapy (RT). We examined our experience in men with IBD who were treated with definitive RT for prostate cancer. Methods and materialsWe queried our institutional database for patients with a diagnosis of ulcerative colitis, Crohn disease, or IBD not otherwise specified. Endpoints were: acute and late ≥grade 2 (G2) GI toxicity and IBD flare after RT. Outcomes were compared with controls using propensity scoring matched 3 to 1. We matched controls to the IBD cohort according to: RT technique, RT dose, risk group, hormone use, treatment year, and age. We determined predictors of acute outcomes using the Fisher exact test and time to outcomes using the log-rank test. ResultsBetween 1990 and 2010, 84 men were included. Sixty-three men served as matched controls and 21 with IBD: 13 ulcerative colitis, 7 Crohn disease, and 1 IBD not otherwise specified. For men with IBD, median age was 69 years, and median follow-up was 49 months. Median flare-free interval before RT was 10 years. Seven were taking IBD medications during RT. There was no difference in acute or late gastrointestinal (GI) toxicity in the IBD group versus controls. Among IBD patients, IBD medication use was the only predictor of acute ≥G2 GI toxicity: 57.1% with medication versus7.7% without (49.4% absolute difference, 95% confidence interval [CI] 10.0%-88.9%, P = .03). The 5-year risk of late GI toxicity in men with IBD versus controls was not statistically significant (hazard ratio = 1.19, 95%CI 0.28-5.01, P = .83). The crude incidence of late ≥G2 GI toxicity was 10%. ConclusionsAcute GI toxicity appears to be exacerbated in patients on concomitant medical therapy for IBD. Overall, late GI toxicity was relatively low and not significantly different between patients with IBD versus no IBD. However, the small sample size limits the interpretation of our estimates and the wide confidence intervals indicate these patients warrant careful selection.

Su1089 The Effects of IBD Patient Self Management Practices on IBD Flares and Patient Outcomes

Su1089 The Effects of IBD Patient Self Management Practices on IBD Flares and Patient Outcomes

Enhanced Blood Lymphocytes Apoptosis in Children with Inflammatory Bowel Disease

The aim of this work was to measure peripheral lymphocyte apoptosis during IBD flare and remission. Subjects and Methods. Flow-cytometric assessment of apoptosis of peripheral blood lymphocytes (PBL) was assessed in 30 children with IBD (16 with ulcerative colitis and 14 with Crohn's disease) compared to 22, age and sex matched, healthy children. This was carried out during a flare, whether in newly diagnosed or relapsing patients, and after achievement of remission. Clinical findings, complete blood count, liver transaminases, and kidney functions were assessed. Results. Early apoptotic and late apoptotic/necrotic lymphocytes were significantly higher during IBD flare compared to controls (P ≤ 0.01 and <0.01, resp., in ulcerative colitis and P ≤ 0.01 and <0.01, resp., in Crohn's disease patients). Remission values were significantly decreased but did not come back to the control levels. Early apoptotic values were significantly related to joint involvement in IBD patients (P < 0.0001). Conclusions. We can speculate a systemic nature of IBD as evident by enhanced peripheral lymphocyte apoptosis. This is related, to a great extent, to the disease process as it is more deranged in flare than in remission. Relation of this derangement to extraintestinal manifestations needs a special attention.

PTH-163 Nurse Led Telephone Clinics- The NHS Revolution in Making

IntroductionPatients under the care of Gastroenterologists suffer from a wide variety of acute and chronic conditions which often need regular intensive monitoring. This often necessitates frequent outpatient visits and follows...

41 Serious Infections and Associated Risk Factors in Patients Receiving Infliximab and Immunotherapies for Children With Inflammatory Bowel Disease: Develop Registry Data

all pts with PSC-IBD who underwent LT for non-cholangiocarcinoma indications at Mayo Clinic, Rochester from 1998-2008, with follow-up through 2012. Information on course of pre-transplant IBD, de novo IBD and colectomy was extracted. Progression of IBD was defined as need for escalation of medical therapy, as compared to pre-LT course. Risk factors for progression of IBD were identified using multivariate Cox proportional hazard analysis. Results: One hundred one pts with PSC underwent LT (mean age, 48 yrs; 62 males). Median follow-up (IQR) was 8.4 years (5.5-10.7). Of these, 80 pts had associated IBD (74 pts with ulcerative colitis, 6 pts with Crohn's disease). Twenty-five pts underwent colectomy prior to LT (18 for medically-refractory IBD, 7 for colorectal neoplasia). Further analysis was restricted to 55 pts with PSC-IBD with intact colon at time of LT. Pre-LT, 32 pts had quiescent IBD requiring no therapy and 21 were maintained on 5-ASA. Post-LT, despite transplant-related immunosuppression, 26/55 (47.3%) required escalation of therapy, whereas 28/55 had a stable course (50.9%) and 1 patient (1.8%) improved (Table). One, 5and 10-year risk of progression of IBD was 10.9%, 36.4% and 45.4%, respectively. Thirteen pts underwent colectomy after LT (5 for medically-refractory IBD, 8 for colorectal neoplasia), with 1-, 5and 10-year risk of colectomy being 1.8%, 16.4% and 21.8%. On multivariate Cox proportional hazard analysis, use of tacrolimus (hazard ratio, 5.6; 95% CI, 1.1-103.4) was associated with progression of IBD, whereas recurrence of PSC (HR, 0.2; 95% CI, 0.1-0.6) was protective against progression of IBD. There was no association between progression of IBD and transplant(CMV infection/mismatch), immunosuppression-(use of mycophenolate, azathioprine or prolonged prednisone use), or IBD-related factors (pretransplant IBD activity, empirical initiation of 5-aminosalicylates within 4 months of LT). Eleven pts developed de novo IBD after LT, with 1-, 5and 10-year risk (among PSC pts without IBD after LT) being 4.8%, 38.1% and 47.6%. No specific transplant or immunosuppression-related risk factor was identified, including CMV infection. Conclusion: The cumulative probability of IBD flare requiring escalation of therapy after LT for PSC is 45% at 10 years, despite immunosuppression for LT. Recurrent PSC was associated with mild course of IBD after LT, similar to the observation that advanced PSC requiring LT is associated with a mild course of IBD pre-transplant.

Clostridium difficile in Inflammatory Bowel Disease

The incidence and severity of Clostridium difficile infection (CDI) have more than doubled over the past decade, leading to increased hospitalization rates and length of stay, with significant morbidity and mortality. It is estimated that the financial burden of CDI on the health care system in the United States costs billions of dollars. Recent studies have demonstrated that patients with inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis) are at an increased risk for developing CDI and experience increased morbidity and mortality, as well as an increased need for emergent colectomy. CDI may mimic an IBD flare, even in patients who have had a colectomy ( C difficile enteritis); thus, a high suspicion should be maintained, as prompt diagnosis and treatment have been shown to improve outcomes. Currently, oral metronidazole is the treatment of choice for mild to moderate CDI, with oral vancomycin being reserved for patients with severe CDI. At this time, there are no clear guidelines for treatment of CDI in patients with IBD; prospective randomized control trials are needed. In this article, we summarize the epidemiology, pathogenesis, risk factors, clinical features, and treatment (both medical and surgical) of CDI in patients with IBD.

Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis

To perform a literature review as basis for the update of the Assessment in SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) treatment recommendations with biologics in AS. A literature search of all publications found in MedLine, Embase and Cochrane database between 2005 and 2009 and in the EULAR/ACR meetings between 2007 and 2009 was performed. The research evidence and strength of recommendation (SOR) for biologics were provided. Out of 247 reports on AS treatment with biologics, 98 contained efficacy data and 25 had complete data for analysis. The treatment effect sizes (95% CI) for anti-TNF vs placebo varied between 0.34 (0.08, 0.6) and 1.5 (0.45, 2.5) for BASDAI and 0.33 (0.07, 0.59) and 2.5 (1.3, 3.7) for BASFI. The calculation of the numbers needed to treat all the different outcomes varied between 2.3 and 3.0 patients for all ASAS outcomes and between 2.7 and 6.5 patients for ASAS partial remission. Data on biologics other than anti-TNF and for TNF blockers on juvenile SpA were limited. The incidence rates of uveitis during anti-TNF treatment varied between 4.4/100 patient-years (pys) and 15.6/100 pys during placebo (P < 0.05). The incidence rates of IBD flares were significantly less during infliximab treatment (0.2/100 pys). The rate of infections was higher in patients treated with anti-TNF as compared with placebo, but there was no difference in the incidence of serious infections for treatment with anti-TNF vs placebo. The overall evidence was very high for anti-TNF treatment (1b, SOR: A) with respect to efficacy and safety, while it was low for biologic treatment other than anti-TNF (3, SOR: C).

Stress causes flares of IBD—how much evidence is enough?

Patients with IBD often believe that stress leads to increased disease activity and symptoms. The major problem with work in this area is that it relies on perception, which is notoriously difficult to quantify. However, a recent study provides evidence to support the possible effect of stress on IBD symptoms.

Are Inflammatory Markers Predictive of Length of Hospital Stay in Patients with Inflammatory Bowel Disease?

Purpose: Formulas such as the Crohn's Disease Activity Index and Harvey Bradshaw Index rely on subjective criteria and have had poorly documented relationships to inflammation in the gut and extraintestinal tissues. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels, however, have served as objective measures of IBD activity. If CRP and ESR forecast severity of disease, then a prolonged hospital stay might be expected. We sought to determine if CRP and ESR were correlated with length of hospital stay (LOS) in IBD patients and if there was a difference in those with Crohn's disease (CD) compared to ulcerative colitis (UC). Methods: IRB-approved retrospective study of 35 IBD patients admitted for an IBD flare in the past 10 years. Inclusion criteria were age >18, diagnosis of UC or CD,ESR and/or CRP taken within the first 2 days of admission, and an admission for an IBD flare. Statistical analysis done using SAS version 9.2. Results: All patients were of AfroCaribbean descent. Seventeen patients had CD and 18 patients had UC. Fourteen patients had IBD for more than 5 years. Mean age was 38 years. Fifteen patients had extraintestinal manifestations (EIM). For all IBD patients, mean CRP level was 62.0 mg/L (normal value <0.4) and mean ESR was 58.7 mm/hr (normal value 0-20). Average LOS was 8.1 days. Correlation of CRP with LOS was r=0.21 (p=0.29) and ESR with LOS r=0.271 (p=0.13). Stronger correlations were found with males (CRP r=0.40 and ESR r=0.48 in males; CRP r=0.22 and ESR r=0.23 in females). No difference was found in those with >5 years of IBD compared to <5 years (p=0.43). No difference was found in those with EIM compared to those without (p=0.79). In UC patients, mean CRP was 56.7 mg/L and ESR was 58 mm/hr, with a mean LOS of 8.9 days. Correlation of CRP with LOS was r=0.36 (p=0.18) and ESR with LOS being r=0.30 (p=0.22). In CD patients, mean CRP was 69 mg/L and ESR was 59 mm/hr, with the mean LOS being 7.2 days. Correlation of CRP with LOS was r=0.02 (p=0.94) and with ESR and LOS r= 0.26(p=0.38). Conclusion: We found no correlation between inflammatory markers and LOS. Differences may not have been seen due to our small sample size. In addition, our results come solely from AfroCaribbeans, an often under-reported group of IBD patients. Whether our findings can be applied to other ethnic IBD populations remain to be seen. No data have been available correlating inflammatory markers and LOS in ethnic populations. We question if stronger correlations could found among other ethnicities given that racial differences in phenotypic expression of IBD have been previously reported. In the meantime, though CRP and ESR have been correlated with disease activity, we do not encourage the use of these markers in forecasting LOS.